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Crawford, Jeffrey

Overview:

1. Lung cancer/new treatment approaches.
2. Clinical trials of hematopoietic growth factors, biological agents and targeted drug development.
3. Cancer in the elderly and supportive care

Accomplishments

1. Lead Investigator of the U. S. multicenter, randomized trial of Filgrastim (G-CSF, Neupogen) to reduce the morbidity of chemotherapy-related neutropenia, leading to FDA approval 2/91.
2. Lead Investigator of the U. S. multicenter, randomized trial of Vinorelbine (Navelbine) in treatment of patients with advanced non small cell carcinoma of lung (NSCLC), leading to FDA approval 12/94.
3. Principal Investigator in initial phase I clinical trials of stem cell factor (SCF), megakaryocyte growth and development factor (MGDF), pegylated granulocyte-colony-stimulating factor and other novel hematopoietic growth factors.

Positions:

George Barth Geller Professor

Medicine, Medical Oncology
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Associate Director of Clinical Research, Comprehensive Cancer Center

Duke Cancer Institute
School of Medicine

Education:

M.D. 1974

M.D. — Ohio State University

Grants:

BR.31

Administered By
Duke Cancer Institute
AwardedBy
Clinipace, Inc.
Role
Principal Investigator
Start Date
February 01, 2016
End Date
January 31, 2026

Phase II anetumab ravtansine as 2nd line treatment for malignant pleural mesothelioma

Administered By
Duke Cancer Institute
AwardedBy
Bayer HealthCare AG
Role
Principal Investigator
Start Date
July 01, 2016
End Date
June 30, 2021

TIGER 1: A randomized, open-label, phase II study of CO-1686 or Erlotinib as first-line treatment of patients with EGFR-Mutant advanced non-small cell lung cancer

Administered By
Duke Cancer Institute
AwardedBy
Clovis Oncology, Inc.
Role
Principal Investigator
Start Date
August 01, 2015
End Date
July 31, 2020

A phase II, Open-label, single-arm study to assess the safety and efficacy of AZD9291 in patients with locally advanced/

Administered By
Duke Cancer Institute
AwardedBy
AstraZeneca AB
Role
Principal Investigator
Start Date
April 01, 2014
End Date
March 31, 2019

NCI National Clinical Trials Network U10 (Year 4)

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 14, 2014
End Date
February 28, 2019

A phase 2, randomized, double-blind study comparing Tremelimumab to placebo in Second- or third-line treatment of subjec

Administered By
Duke Cancer Institute
AwardedBy
MedImmune, Inc.
Role
Principal Investigator
Start Date
October 01, 2013
End Date
September 30, 2018

Identification of Genetic Determinates for Disparities in African American Patients with Non-Small Cell Lung Cancer

Administered By
Medicine, Medical Oncology
AwardedBy
V Foundation for Cancer Research
Role
Significant Contributor
Start Date
November 01, 2016
End Date
November 01, 2017

A phase III, double-blind, randomized, placebo-controlled study to assess the efficacy and safety of selumetinib (AZD624

Administered By
Duke Cancer Institute
AwardedBy
AstraZeneca Pharmaceuticals, LP
Role
Principal Investigator
Start Date
February 01, 2014
End Date
December 31, 2016

FibroGen, Inc. FGCL-3019-073

Administered By
Duke Cancer Institute
AwardedBy
Fibrogen, Inc.
Role
Principal Investigator
Start Date
May 01, 2015
End Date
May 02, 2016

MORAb-009-021

Administered By
Duke Cancer Institute
AwardedBy
Morphotek, Inc
Role
Principal Investigator
Start Date
April 01, 2016
End Date
April 30, 2016

A Decision Aid with HRQL Assessment to Reduce Costs in the Treatment of NSCLC

Administered By
Medicine, Medical Oncology
AwardedBy
University of Virginia - Charlottesville
Role
Principal Investigator
Start Date
September 01, 2012
End Date
August 31, 2015

ANC Study Group

Administered By
Medicine, Medical Oncology
AwardedBy
Fred Hutchinson Cancer Research Center
Role
Principal Investigator
Start Date
April 30, 2014
End Date
June 30, 2014

Cancer and Leukemia Group B

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 23, 2009
End Date
February 28, 2014

Research Training in Cancer Biology and Therapy

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1978
End Date
July 31, 2013

Refining and Validating Genomic Signatures in Lung Cancer

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
August 14, 2009
End Date
December 31, 2010

Prospective Validation of Genomic Signatures of Chemosensitivity in NSCLC

Administered By
Institutes and Centers
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
January 01, 2009
End Date
November 30, 2010

Biomarker Studies for Novel Anti-Cancer Agents

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
May 28, 2003
End Date
February 29, 2008

Phase I/II Trial of ZD1839 and Celecoxib in Ex-Smokers

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 26, 2002
End Date
August 31, 2007

Measurement of Hypoxia in Non-Small Cell Lung Carcinoma

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
April 01, 2002
End Date
March 31, 2006

Dexasome Based Immunotherapy of Lung Cancer

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
March 01, 2001
End Date
February 28, 2004

Cancer and Leukemia Group B

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1998
End Date
March 31, 2003

Cancer and Leukemia Group B

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1988
End Date
March 31, 2003

Cancer and Leukemia Group B

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1988
End Date
March 31, 2003

Using Plasma TGFB1 Levels to Escalate Radiotherapy Doses

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
February 15, 2000
End Date
January 31, 2003

Cancer Center Core Support Grant

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1976
End Date
December 31, 1998

Comprehensive Cancer Center Core Support Grant

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1976
End Date
December 31, 1998

Comprehensive Cancer Center Core Support Grant

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 01, 1976
End Date
December 31, 1998

Cancer And Leukemia Group B

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 06, 1993
End Date
March 31, 1998

Cancer And Leukemia Group B

Administered By
Medicine, Medical Oncology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 1988
End Date
March 31, 1998
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Publications:

Phase I study of pazopanib plus TH-302 in advanced solid tumors.

To define the maximum tolerated dose (MTD), recommended phase II dose (RPTD), and assess safety and tolerability for the combination of pazopanib plus TH-302, an investigational hypoxia-activated prodrug (HAP), in adult patients with advanced solid tumors.This was an open-label, non-randomized, single-center, phase I trial consisting 2 stages. Stage 1 was a standard "3 + 3" dose escalation design to determine safety and the RPTD for TH-302 plus pazopanib combination. Stage 2 was an expanded cohort to better describe the tolerability and toxicity profile at the MTD. Pazopanib was orally dosed at 800 mg daily on days 1-28 for all cohorts. TH-302 was administered intravenously on days 1, 8 and 15 of a 28-day cycle at doses of 340 mg/m2 (cohort 1) or 480 mg/m2 (cohort 2). Dose limiting toxicity (DLT) was assessed in the first 28-day cycle. Efficacy was assessed every 2 cycles.Thirty patients were enrolled between December 2011 and September 2013. In the dose escalation stage, 7 patients were enrolled in the 340 mg/m2 TH-302 cohort and 6 patients in the 480 mg/m2 TH-302 cohort. Ten patients were evaluable for DLT. DLTs included grade 2 intolerable esophagitis (n = 1) in the 340 mg/m2 TH-302 cohort, and grade 3 vaginal inflammation (n = 1) and grade 3 neutropenia with grade 3 thrombocytopenia (n = 1, same patient) in the 480 mg/m2 TH-302 cohort. The 340 mg/m2 TH-302 cohort was determined to be MTD and RPTD. The most common treatment-related adverse events were hematologic (anemia, neutropenia, and thrombocytopenia), nausea/vomiting, palmar-plantar erythrodysesthesia syndrome, constipation, fatigue, mucositis, anorexia, pain, and hypertension. Partial response (PR) was observed in 10% (n = 3) of patients, stable disease (SD) in 57% (n = 17), and progressive disease (PD) in 23% (n = 7). Due to toxicity, 3 patients were discontinued from study drug prior to first radiographic assessment but were included in these calculations. Disease control ≥6 months was observed in 37% of patients (n = 11).The RPTD for this novel combination is pazopanib 800 mg daily on days 1-28 plus TH-302 340 mg/m2 on days 1, 8 and 15 of each 28-day cycle. Preliminary activity was seen in treatment-refractory cancers and supports potential value of co-targeting tumor angiogenesis and tumor hypoxia.

Authors
Riedel, RF; Meadows, KL; Lee, PH; Morse, MA; Uronis, HE; Blobe, GC; George, DJ; Crawford, J; Niedzwiecki, D; Rushing, CN; Arrowood, CC; Hurwitz, HI
MLA Citation
Riedel, RF, Meadows, KL, Lee, PH, Morse, MA, Uronis, HE, Blobe, GC, George, DJ, Crawford, J, Niedzwiecki, D, Rushing, CN, Arrowood, CC, and Hurwitz, HI. "Phase I study of pazopanib plus TH-302 in advanced solid tumors." Cancer chemotherapy and pharmacology 79.3 (March 2017): 611-619.
PMID
28238078
Source
epmc
Published In
Cancer Chemotherapy and Pharmacology
Volume
79
Issue
3
Publish Date
2017
Start Page
611
End Page
619
DOI
10.1007/s00280-017-3256-2

Validation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials.

The aim of this study was to investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma.Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual-level surrogacy was assessed by Kendall's tau through a Clayton bivariate Copula survival (CBCS) model. Summary-level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)-log HROS and log HRPFS-measured in R2 from a weighted least-square (WLS) regression model and the CBCS model.The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8-3.5 months) and the median OS was 7.2 months (95% CI, 6.5-8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall's tau ranging from 0.46 to 0.47. The summary-level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age.The analyses demonstrated low to moderate individual-level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma. The Oncologist 2017;22:189-198Implications for Practice: For better disease management and for more efficient clinical trial designs, it is important to know if progression-free survival (PFS) is a good surrogate endpoint for overall survival in malignant mesothelioma. With a relatively large database of 17 phase II trials and 716 patients from Cancer and Leukemia Group B and North Central Cancer Treatment Group, we conducted statistical analyses and found that there is no evidence to suggest that PFS is a valid surrogate endpoint for OS for malignant mesothelioma. Future research work is needed to find alternative surrogate endpoints for OS.

Authors
Wang, X; Wang, X; Hodgson, L; George, SL; Sargent, DJ; Foster, NR; Ganti, AK; Stinchcombe, TE; Crawford, J; Kratzke, R; Adjei, AA; Kindler, HL; Vokes, EE; Pang, H
MLA Citation
Wang, X, Wang, X, Hodgson, L, George, SL, Sargent, DJ, Foster, NR, Ganti, AK, Stinchcombe, TE, Crawford, J, Kratzke, R, Adjei, AA, Kindler, HL, Vokes, EE, and Pang, H. "Validation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials." The oncologist 22.2 (February 10, 2017): 189-198.
PMID
28188257
Source
epmc
Published In
The oncologist
Volume
22
Issue
2
Publish Date
2017
Start Page
189
End Page
198
DOI
10.1634/theoncologist.2016-0121

Phase II Study of Dasatinib in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer.

The Src pathway in activated in about one-third of non-small cell lung cancer (NSCLC) tumors. Dasatinib has Src-inhibitor activity. We examined the activity of dasatinib in 37 patients with advanced, previously treated NSCLC. Among the 29 patients who underwent pre-treatment biopsy for RNA biomarker analysis, 25 were treated with dasatinib 70 mg twice daily. There were no responses. Five patients discontinued treatment due to toxicity. Three patients had minor biopsy-related pneumothoraces. Given the lack of responses, no biomarkers were analyzed. Dasatinib 70 mg twice daily does not have activity nor is it well tolerated in unselected patients with advanced stage, previously treated NSCLC.

Authors
Kelley, MJ; Jha, G; Shoemaker, D; Herndon, JE; Gu, L; Barry, WT; Crawford, J; Ready, N
MLA Citation
Kelley, MJ, Jha, G, Shoemaker, D, Herndon, JE, Gu, L, Barry, WT, Crawford, J, and Ready, N. "Phase II Study of Dasatinib in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer." Cancer investigation 35.1 (January 2017): 32-35.
PMID
27911119
Source
epmc
Published In
Cancer Investigation (Informa)
Volume
35
Issue
1
Publish Date
2017
Start Page
32
End Page
35
DOI
10.1080/07357907.2016.1253710

Patterns of Failure After Surgery for Non-Small-cell Lung Cancer Invading the Chest Wall.

The patterns of failure after resection of non-small-cell lung cancer (NSCLC) invading the chest wall are not well documented, and the role of adjuvant radiation therapy (RT) is unclear, prompting the present analysis.The present institutional review board-approved study evaluated patients who had undergone surgery from 1995 to 2014 for localized NSCLC invading the chest wall. Patients with superior sulcus tumors were excluded. The clinical outcomes were estimated using the Kaplan-Meier method and compared using a log-rank test. The prognostic factors were assessed using a multivariate analysis, and the patterns of failure were scored.Seventy-four patients were evaluated. Most patients had undergone lobectomy or pneumonectomy (85%) with en bloc chest wall resection (80%) and had pathologically node negative findings (81%). The surgical margins were positive in 10 patients (14%) and most commonly involved the chest wall (7 of 10). Adjuvant treatment included RT in 21 (28%) and chemotherapy in 28 (38%). A total of 24 local recurrences developed. The chest wall was a component of local disease recurrence in 19 of 24 cases (79%). The local control rate at 5 years for the entire population was 60% (95% confidence interval, 46%-74%). The local control rate was 74% with adjuvant RT versus 55% without RT (P = .43). On multivariate analysis, only resection less than lobectomy or pneumonectomy was associated with worse local control. The overall survival rate was 38% with RT versus 34% without RT (P = .59).Positive surgical margins and local disease recurrence were common after resection of NSCLC invading the chest wall. The primary pattern of failure was local recurrence in the chest wall. Adjuvant RT was not associated with improved local control or survival.

Authors
Tandberg, DJ; Kelsey, CR; D'Amico, TA; Crawford, J; Chino, JP; Tong, BC; Ready, NE; Wright, A
MLA Citation
Tandberg, DJ, Kelsey, CR, D'Amico, TA, Crawford, J, Chino, JP, Tong, BC, Ready, NE, and Wright, A. "Patterns of Failure After Surgery for Non-Small-cell Lung Cancer Invading the Chest Wall." Clinical lung cancer (November 21, 2016).
PMID
27965012
Source
epmc
Published In
Clinical lung cancer
Publish Date
2016
DOI
10.1016/j.cllc.2016.11.008

Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer.

To determine the feasibility and toxicity of radiation therapy, delivered either as definitive treatment or following surgery, following neo-adjuvant immune checkpoint inhibition for locally advanced NSCLC sixteen patients who received neo-adjuvant chemotherapy including ipilimumab as part of a phase II study were identified. Patients were analyzed by intent of radiation and toxicity graded based on CTCAE 4.0. There were seven patients identified who received definitive radiation and nine who received post-operative radiation. There was no grade 3 or greater toxicity in the definitive treatment group although one patient stopped treatment early due to back pain secondary to progression outside of the treatment field. In the post-operative treatment group, one patient required a one week break due to grade 2 odynophagia and no grade 3 or greater toxicity was observed. In this study of radiation as definitive or post-operative treatment following neo-adjuvant chemotherapy including ipilimumab for locally advanced NSCLC was feasible and well tolerated with limited toxicity.

Authors
Boyer, MJ; Gu, L; Wang, X; Kelsey, CR; Yoo, DS; Onaitis, MW; Dunphy, FR; Crawford, J; Ready, NE; Salama, JK
MLA Citation
Boyer, MJ, Gu, L, Wang, X, Kelsey, CR, Yoo, DS, Onaitis, MW, Dunphy, FR, Crawford, J, Ready, NE, and Salama, JK. "Toxicity of definitive and post-operative radiation following ipilimumab in non-small cell lung cancer." Lung cancer (Amsterdam, Netherlands) 98 (August 2016): 76-78.
PMID
27393510
Source
epmc
Published In
Lung Cancer
Volume
98
Publish Date
2016
Start Page
76
End Page
78
DOI
10.1016/j.lungcan.2016.05.014

Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials).

Muscle wasting in cancer is a common and often occult condition that can occur prior to overt signs of weight loss and before a clinical diagnosis of cachexia can be made. Muscle wasting in cancer is an important and independent predictor of progressive functional impairment, decreased quality of life, and increased mortality. Although several therapeutic agents are currently in development for the treatment of muscle wasting or cachexia in cancer, the majority of these agents do not directly inhibit muscle loss. Selective androgen receptor modulators (SARMs) have the potential to increase lean body mass (LBM) and hence muscle mass, without the untoward side effects seen with traditional anabolic agents. Enobosarm, a nonsteroidal SARM, is an agent in clinical development for prevention and treatment of muscle wasting in patients with cancer (POWER 1 and 2 trials). The POWER trials are two identically designed randomized, double-blind, placebo-controlled, multicenter, and multinational phase 3 trials to assess the efficacy of enobosarm for the prevention and treatment of muscle wasting in subjects initiating first-line chemotherapy for non-small-cell lung cancer (NSCLC). To assess enobosarm's effect on both prevention and treatment of muscle wasting, no minimum weight loss is required. These pivotal trials have pioneered the methodological and regulatory fields exploring a therapeutic agent for cancer-associated muscle wasting, a process hereby described. In each POWER trial, subjects will receive placebo (n = 150) or enobosarm 3 mg (n = 150) orally once daily for 147 days. Physical function, assessed as stair climb power (SCP), and LBM, assessed by dual-energy X-ray absorptiometry (DXA), are the co-primary efficacy endpoints in both trials assessed at day 84. Based on extensive feedback from the US Food and Drug Administration (FDA), the co-primary endpoints will be analyzed as a responder analysis. To be considered a physical function responder, a subject must have ≥10 % improvement in physical function compared to baseline. To meet the definition of response on LBM, a subject must have demonstrated no loss of LBM compared with baseline. Secondary endpoints include durability of response assessed at day 147 in those responding at day 84. A combined overall survival analysis for both studies is considered a key secondary safety endpoint. The POWER trials design was established with extensive clinical input and collaboration with regulatory agencies. The efficacy endpoints are a result of this feedback and discussion of the threshold for clinical benefit in patients at risk for muscle wasting. Full results from these studies will soon be published and will further guide the development of future anabolic trials. Clinical Trial ID: NCT01355484. https://clinicaltrials.gov/ct2/show/NCT01355484 , NCT01355497. https://clinicaltrials.gov/ct2/show/NCT01355497?term=g300505&rank=1 .

Authors
Crawford, J; Prado, CMM; Johnston, MA; Gralla, RJ; Taylor, RP; Hancock, ML; Dalton, JT
MLA Citation
Crawford, J, Prado, CMM, Johnston, MA, Gralla, RJ, Taylor, RP, Hancock, ML, and Dalton, JT. "Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials)." Current oncology reports 18.6 (June 2016): 37-. (Review)
PMID
27138015
Source
epmc
Published In
Current Oncology Reports
Volume
18
Issue
6
Publish Date
2016
Start Page
37
DOI
10.1007/s11912-016-0522-0

Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies.

Sotatercept may represent a novel approach to the treatment of chemotherapy-induced anemia (CIA). We report the results from two phase 2 randomized studies examining the use of sotatercept for the treatment of CIA in patients with metastatic cancer.In study A011-08, patients with metastatic breast cancer were randomized to 2:2:2:1 to receive sotatercept 0.1, 0.3, or 0.5 mg/kg, or placebo, respectively, every 28 days. In study ACE-011-NSCL-001, patients with solid tumors treated with platinum-based chemotherapy received sotatercept 15 or 30 mg every 42 days. The primary endpoint for both studies was hematopoietic response, defined as a hemoglobin (Hb) increase of ≥1 g/dL from baseline.Both studies were terminated early due to slow patient accrual. Among patients treated with sotatercept in the A011-08 and ACE-011-NSCL-001 studies, more patients achieved a mean Hb increase of ≥1 g/dL in the combined sotatercept 0.3 mg/kg and 15 mg (66.7 %) group and sotatercept 0.5 mg/kg and 30 mg (38.9 %) group versus the sotatercept 0.1 mg/kg (0 %) group. No patients achieved a mean Hb increase of ≥1 g/dL in the placebo group. The incidence of treatment-related adverse events (AEs) was low in both studies, and treatment discontinuations due to AEs were uncommon.Although both studies were terminated early, these results indicate that sotatercept is active and has an acceptable safety profile in the treatment of CIA.

Authors
Raftopoulos, H; Laadem, A; Hesketh, PJ; Goldschmidt, J; Gabrail, N; Osborne, C; Ali, M; Sherman, ML; Wang, D; Glaspy, JA; Puccio-Pick, M; Zou, J; Crawford, J
MLA Citation
Raftopoulos, H, Laadem, A, Hesketh, PJ, Goldschmidt, J, Gabrail, N, Osborne, C, Ali, M, Sherman, ML, Wang, D, Glaspy, JA, Puccio-Pick, M, Zou, J, and Crawford, J. "Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies." Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 24.4 (April 2016): 1517-1525.
PMID
26370220
Source
epmc
Published In
Supportive Care in Cancer
Volume
24
Issue
4
Publish Date
2016
Start Page
1517
End Page
1525
DOI
10.1007/s00520-015-2929-9

Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE).

Prophylactic cranial irradiation (PCI) has become a standard option for patients with extensive-stage small cell lung cancer (ES-SCLC). The Cancer and Leukemia Group B 30504 trial was a randomized phase II study of the effect of sunitinib versus placebo in ES-SCLC patients responding to platinum-based systemic therapy. The study required preenrollment brain imaging. PCI was provided at the discretion of treating physicians. We performed a secondary analysis of the Cancer and Leukemia Group B trial to determine the impact of PCI on patients with ES-SCLC.Fisher's exact test and the Wilcoxon rank-sum test were conducted to identify the differences between patients receiving PCI and patients not receiving PCI. Kaplan-Meier analyses described progression-free survival (PFS) and overall survival (OS) for patients in the PCI and non-PCI groups.A total of 85 patients received maintenance therapy (41 received placebo and 44 received sunitinib). Patient characteristics were balanced between the PCI and non-PCI groups. The patients receiving PCI plus sunitinib had a nonsignificant 2.7-month improvement in PFS (5.0 months versus 2.3 months, p = 0.14, hazard risk [HR] = 0.62, 95% confidence interval [CI]: 0.33-1.18) trending toward improved OS (8.9 months versus 5.4 months, p = 0.053, HR = 0.47, 95% CI: 0.22-1.03). PCI was associated with a trend toward improved median PFS (2.9 months versus 2.2 months, p = 0.096, HR = 0.69, 95% CI: 0.45-1.07) but not median OS (8.3 months in the PCI group versus 8.7 months in the non-PCI group, p = 0.76, HR = 1.07, 95% CI: 0.67-1.71). The patients receiving placebo had no improvement in PFS or OS with PCI.Trends toward improved PFS and OS were seen in patients receiving PCI and sunitinib, thus supporting the need for further prospective research evaluating the integration of maintenance systemic therapy and PCI for patients with ES-SCLC. Improved outcomes for patients with ES-SCLC after induction chemotherapy may require PCI, thoracic radiotherapy, and maintenance systemic therapy to achieve control of both intracranial and extracranial disease.

Authors
Salama, JK; Gu, L; Wang, X; Pang, HH; Bogart, JA; Crawford, J; Schild, SE; Vokes, EE; Ready, NE
MLA Citation
Salama, JK, Gu, L, Wang, X, Pang, HH, Bogart, JA, Crawford, J, Schild, SE, Vokes, EE, and Ready, NE. "Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE)." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 11.3 (March 2016): 361-369.
PMID
26723241
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
11
Issue
3
Publish Date
2016
Start Page
361
End Page
369
DOI
10.1016/j.jtho.2015.11.001

Request for regulatory guidance for cancer cachexia intervention trials.

Authors
Fearon, K; Argiles, JM; Baracos, VE; Bernabei, R; Coats, A; Crawford, J; Deutz, NE; Doehner, W; Evans, WJ; Ferrucci, L; Garcia, JM; Gralla, RJ; Jatoi, A; Kalantar-Zadeh, K; Lainscak, M; Morley, JE; Muscaritoli, M; Polkey, MI; Rosano, G; Rossi-Fanelli, F; Schols, AM; Strasser, F; Vellas, B; von Haehling, S; Anker, SD
MLA Citation
Fearon, K, Argiles, JM, Baracos, VE, Bernabei, R, Coats, A, Crawford, J, Deutz, NE, Doehner, W, Evans, WJ, Ferrucci, L, Garcia, JM, Gralla, RJ, Jatoi, A, Kalantar-Zadeh, K, Lainscak, M, Morley, JE, Muscaritoli, M, Polkey, MI, Rosano, G, Rossi-Fanelli, F, Schols, AM, Strasser, F, Vellas, B, von Haehling, S, and Anker, SD. "Request for regulatory guidance for cancer cachexia intervention trials." Journal of cachexia, sarcopenia and muscle 6.4 (December 2015): 272-274.
Website
http://hdl.handle.net/10161/13028
PMID
26675232
Source
epmc
Published In
Journal of Cachexia, Sarcopenia and Muscle
Volume
6
Issue
4
Publish Date
2015
Start Page
272
End Page
274
DOI
10.1002/jcsm.12083

Validation of survival prognostic models for non-small-cell lung cancer in stage- and age-specific groups.

Prognostic models have been proposed to predict survival for non-small-cell lung cancer (NSCLC). It is important to evaluate whether these models perform better than performance status (PS) alone in stage- and age-specific subgroups.The validation cohort included 2060 stage I and 1611 stage IV NSCLC patients from 23CALGB studies. For stage I, Blanchon (B), Chansky (C) and Gail (G) models were evaluated along with the PS only model. For stage IV, Blanchon (B) and Mandrekar (M) models were compared with the PS only model. The c-index was used to assess the concordance between survival and risk scores. The c-index difference (c-difference) and the integrated discrimination improvement (IDI) were used to determine the improvement of these models over the PS only model.For stage I, B and PS have better survival separation. The c-index for B, PS, C and G are 0.61, 0.58, 0.57 and 0.52, respectively, and B performs significantly better than PS with c-difference=0.034. For stage IV, B, M and PS have c-index 0.61, 0.64 and 0.60, respectively; B and M perform significantly better than PS with c-difference=0.015 and 0.033, respectively.Although some prognostic models have better concordance with survival than the PS only model, the absolute improvement is small. More accurate prognostic models should be developed; the inclusion of tumor genetic variants may improve prognostic models.

Authors
Wang, X; Gu, L; Zhang, Y; Sargent, DJ; Richards, W; Ganti, AK; Crawford, J; Cohen, HJ; Stinchcombe, T; Vokes, E; Pang, H
MLA Citation
Wang, X, Gu, L, Zhang, Y, Sargent, DJ, Richards, W, Ganti, AK, Crawford, J, Cohen, HJ, Stinchcombe, T, Vokes, E, and Pang, H. "Validation of survival prognostic models for non-small-cell lung cancer in stage- and age-specific groups." Lung cancer (Amsterdam, Netherlands) 90.2 (November 2015): 281-287.
PMID
26319317
Source
epmc
Published In
Lung Cancer
Volume
90
Issue
2
Publish Date
2015
Start Page
281
End Page
287
DOI
10.1016/j.lungcan.2015.08.007

Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update.

To update the 2006 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSFs).The American Society of Clinical Oncology convened an Update Committee and conducted a systematic review of randomized clinical trials, meta-analyses, and systematic reviews from October 2005 through September 2014. Guideline recommendations were based on the review of the evidence by the Update Committee.Changes to previous recommendations include the addition of tbo-filgrastim and filgrastim-sndz, moderation of the recommendation regarding routine use of CSFs in older patients with diffuse aggressive lymphoma, and addition of recommendations against routine dose-dense chemotherapy in lymphoma and in favor of high-dose-intensity chemotherapy in urothelial cancer. The Update Committee did not address recommendations regarding use of CSFs in acute myeloid leukemia or myelodysplastic syndromes in adults.Prophylactic use of CSFs to reduce the risk of febrile neutropenia is warranted when the risk of febrile neutropenia is approximately 20% or higher and no other equally effective and safe regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of febrile neutropenia in patients who are at high risk on the basis of age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. Dose-dense regimens that require CSFs should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death as a result of injury to other organs, include the prompt administration of CSFs.

Authors
Smith, TJ; Bohlke, K; Lyman, GH; Carson, KR; Crawford, J; Cross, SJ; Goldberg, JM; Khatcheressian, JL; Leighl, NB; Perkins, CL; Somlo, G; Wade, JL; Wozniak, AJ; Armitage, JO
MLA Citation
Smith, TJ, Bohlke, K, Lyman, GH, Carson, KR, Crawford, J, Cross, SJ, Goldberg, JM, Khatcheressian, JL, Leighl, NB, Perkins, CL, Somlo, G, Wade, JL, Wozniak, AJ, and Armitage, JO. "Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33.28 (October 2015): 3199-3212.
PMID
26169616
Source
epmc
Published In
Journal of Clinical Oncology
Volume
33
Issue
28
Publish Date
2015
Start Page
3199
End Page
3212
DOI
10.1200/jco.2015.62.3488

Assessing patients' risk of febrile neutropenia: is there a correlation between physician-assessed risk and model-predicted risk?

This study evaluated the correlation between the risk of febrile neutropenia (FN) estimated by physicians and the risk of severe neutropenia or FN predicted by a validated multivariate model in patients with nonmyeloid malignancies receiving chemotherapy. Before patient enrollment, physician and site characteristics were recorded, and physicians self-reported the FN risk at which they would typically consider granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (FN risk intervention threshold). For each patient, physicians electronically recorded their estimated FN risk, orders for G-CSF primary prophylaxis (yes/no), and patient characteristics for model predictions. Correlations between physician-assessed FN risk and model-predicted risk (primary endpoints) and between physician-assessed FN risk and G-CSF orders were calculated. Overall, 124 community-based oncologists registered; 944 patients initiating chemotherapy with intermediate FN risk enrolled. Median physician-assessed FN risk over all chemotherapy cycles was 20.0%, and median model-predicted risk was 17.9%; the correlation was 0.249 (95% CI, 0.179-0.316). The correlation between physician-assessed FN risk and subsequent orders for G-CSF primary prophylaxis (n = 634) was 0.313 (95% CI, 0.135-0.472). Among patients with a physician-assessed FN risk ≥ 20%, 14% did not receive G-CSF orders. G-CSF was not ordered for 16% of patients at or above their physician's self-reported FN risk intervention threshold (median, 20.0%) and was ordered for 21% below the threshold. Physician-assessed FN risk and model-predicted risk correlated weakly; however, there was moderate correlation between physician-assessed FN risk and orders for G-CSF primary prophylaxis. Further research and education on FN risk factors and appropriate G-CSF use are needed.

Authors
Lyman, GH; Dale, DC; Legg, JC; Abella, E; Morrow, PK; Whittaker, S; Crawford, J
MLA Citation
Lyman, GH, Dale, DC, Legg, JC, Abella, E, Morrow, PK, Whittaker, S, and Crawford, J. "Assessing patients' risk of febrile neutropenia: is there a correlation between physician-assessed risk and model-predicted risk?." Cancer medicine 4.8 (August 2015): 1153-1160.
PMID
25810005
Source
epmc
Published In
Cancer Medicine
Volume
4
Issue
8
Publish Date
2015
Start Page
1153
End Page
1160
DOI
10.1002/cam4.454

The effect of filgrastim or pegfilgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy.

Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is associated with higher chemotherapy relative dose intensity, which may lead to improved outcomes; however, the association between G-CSF primary prophylaxis and overall survival (OS) is not well characterized. This study assessed the effect of G-CSF primary prophylaxis on patient outcomes in randomized, controlled, registrational clinical trials of filgrastim and pegfilgrastim.Three placebo-controlled and two non-inferiority clinical trials of filgrastim and/or pegfilgrastim in patients receiving myelosuppressive chemotherapy for lung, breast, or colorectal cancer were included. The median OS, 6- and 12-month survival rates, and hazard ratios [HRs; unadjusted Cox model with 95% confidence intervals (CIs)] were estimated for patients receiving ≥1 dose of filgrastim, pegfilgrastim, or placebo. Comparisons were based on a log-rank test. A fixed-effect meta-analysis assessed the effect of primary prophylaxis with filgrastim/pegfilgrastim on OS in the placebo-controlled trials.In patients with lung cancer receiving filgrastim versus placebo, the median OS was 14.1 versus 11.1 months (HR, 0.81; 95% CI 0.48-1.35; P = 0.412); in patients who crossed over to filgrastim from placebo after cycle 1, the median OS was 16.9 months (HR, 0.75; 95% CI 0.43-1.28; P = 0.286). The median OS was inestimable in at least one treatment arm in the other studies because of the small number of OS events. Where estimable, 6- and 12-month survival rates were generally greater among patients receiving filgrastim/pegfilgrastim versus placebo. In the meta-analysis of placebo-controlled studies comparing G-CSF primary prophylaxis with placebo in the as-treated analysis sets, the HR (95% CI) for OS was 0.77 (0.58-1.03).In this retrospective analysis, OS point estimates were greater among patients receiving filgrastim versus placebo, but the differences were not statistically significant. Further studies evaluating patient outcomes with G-CSF prophylaxis are warranted.NCT00035594, NCT00094809.

Authors
Lyman, GH; Reiner, M; Morrow, PK; Crawford, J
MLA Citation
Lyman, GH, Reiner, M, Morrow, PK, and Crawford, J. "The effect of filgrastim or pegfilgrastim on survival outcomes of patients with cancer receiving myelosuppressive chemotherapy." Annals of oncology : official journal of the European Society for Medical Oncology 26.7 (July 2015): 1452-1458.
PMID
25851633
Source
epmc
Published In
Annals of Oncology
Volume
26
Issue
7
Publish Date
2015
Start Page
1452
End Page
1458
DOI
10.1093/annonc/mdv174

Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance).

To evaluate the efficacy of maintenance sunitinib after chemotherapy for small-cell lung cancer (SCLC).The Cancer and Leukemia Group B 30504 trial was a randomized, placebo-controlled, phase II study that enrolled patients before chemotherapy (cisplatin 80 mg/m(2) or carboplatin area under the curve of 5 on day 1 plus etoposide 100 mg/m(2) per day on days 1 to 3 every 21 days for four to six cycles). Patients without progression were randomly assigned 1:1 to placebo or sunitinib 37.5 mg per day until progression. Cross-over after progression was allowed. The primary end point was progression-free survival (PFS) from random assignment for maintenance placebo versus sunitinib using a one-sided log-rank test with α = .15; 80 randomly assigned patients provided 89% power to detect a hazard ratio (HR) of 1.67.One hundred forty-four patients were enrolled; 138 patients received chemotherapy. Ninety-five patients were randomly assigned; 10 patients did not receive maintenance therapy (five on each arm). Eighty-five patients received maintenance therapy (placebo, n = 41; sunitinib, n = 44). Grade 3 adverse events with more than 5% incidence were fatigue (19%), decreased neutrophils (14%), decreased leukocytes (7%), and decreased platelets (7%) for sunitinib and fatigue (10%) for placebo; grade 4 adverse events were GI hemorrhage (n = 1) and pancreatitis, hypocalcemia, and elevated lipase (n = 1; all in same patient) for sunitinib and thrombocytopenia (n = 1) and hypernatremia (n = 1) for placebo. Median PFS on maintenance was 2.1 months for placebo and 3.7 months for sunitinib (HR, 1.62; 70% CI, 1.27 to 2.08; 95% CI, 1.02 to 2.60; one-sided P = .02). Median overall survival from random assignment was 6.9 months for placebo and 9.0 months for sunitinib (HR, 1.28; 95% CI, 0.79 to 2.10; one-sided P = .16). Three sunitinib and no placebo patients achieved complete response during maintenance. Ten (77%) of 13 patients evaluable after cross-over had stable disease on sunitinib (6 to 27 weeks).Maintenance sunitinib was safe and improved PFS in extensive-stage SCLC.

Authors
Ready, NE; Pang, HH; Gu, L; Otterson, GA; Thomas, SP; Miller, AA; Baggstrom, M; Masters, GA; Graziano, SL; Crawford, J; Bogart, J; Vokes, EE
MLA Citation
Ready, NE, Pang, HH, Gu, L, Otterson, GA, Thomas, SP, Miller, AA, Baggstrom, M, Masters, GA, Graziano, SL, Crawford, J, Bogart, J, and Vokes, EE. "Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33.15 (May 2015): 1660-1665.
PMID
25732163
Source
epmc
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015
Start Page
1660
End Page
1665
DOI
10.1200/jco.2014.57.3105

Accuracy of positron emission tomography in identifying hilar (N1) lymph node involvement in non-small cell lung cancer: Implications for stereotactic body radiation therapy

© 2015 American Society for Radiation Oncology.Purpose: To assess the efficacy of preoperative positron emission tomography (PET) to stage the ipsilateral hilum in resected non-small cell lung cancer (NSCLC). Methods and materials: All patients who underwent surgery for NSCLC between 1995 and 2008 were evaluated. Patients who underwent preoperative PET imaging at our institution and had hilar nodal sampling were included. Those whose primary tumors extended to the hilum or who received preoperative chemotherapy or radiation therapy were excluded. All PET studies were interpreted by an attending nuclear medicine radiologist and were scored as positive or negative in the hilum or peribronchial area based on visual analysis alone. A 2-sided Fisher exact test compared patient subgroups. Results: During the time interval, 1558 patients underwent surgery for NSCLC, of whom 484 were eligible for this analysis. The ipsilateral hilum was positive on preoperative PET in 107 patients. The median number of N1 lymph nodes sampled was 4 (range, 1-31). Positive ipsilateral N1 lymph nodes were identified pathologically in 91 patients (19%). Among the 91 patients with involved N1 lymph nodes, 40 were PET positive resulting in a sensitivity of 44%. Among 393 patients without pathologic involvement of hilar lymph nodes, 326 were PET negative resulting in a specificity of 83%. The positive predictive and negative predictive values were 37% and 86%, respectively. Conclusions: Positron emission tomography appears to have limitations in staging the ipsilateral hilar lymph nodes. Invasive sampling is appropriate if treatment would differ based on the nodal status.

Authors
Pepek, JM; Marks, LB; Berry, MF; Ready, NE; Gee, NG; Coleman, RE; D'Amico, TA; Crawford, J; Kelsey, CR
MLA Citation
Pepek, JM, Marks, LB, Berry, MF, Ready, NE, Gee, NG, Coleman, RE, D'Amico, TA, Crawford, J, and Kelsey, CR. "Accuracy of positron emission tomography in identifying hilar (N1) lymph node involvement in non-small cell lung cancer: Implications for stereotactic body radiation therapy." Practical Radiation Oncology 5.2 (March 1, 2015): 79-84.
Source
scopus
Published In
Practical Radiation Oncology
Volume
5
Issue
2
Publish Date
2015
Start Page
79
End Page
84
DOI
10.1016/j.prro.2014.05.002

Accuracy of positron emission tomography in identifying hilar (N1) lymph node involvement in non-small cell lung cancer: Implications for stereotactic body radiation therapy.

To assess the efficacy of preoperative positron emission tomography (PET) to stage the ipsilateral hilum in resected non-small cell lung cancer (NSCLC).All patients who underwent surgery for NSCLC between 1995 and 2008 were evaluated. Patients who underwent preoperative PET imaging at our institution and had hilar nodal sampling were included. Those whose primary tumors extended to the hilum or who received preoperative chemotherapy or radiation therapy were excluded. All PET studies were interpreted by an attending nuclear medicine radiologist and were scored as positive or negative in the hilum or peribronchial area based on visual analysis alone. A 2-sided Fisher exact test compared patient subgroups.During the time interval, 1558 patients underwent surgery for NSCLC, of whom 484 were eligible for this analysis. The ipsilateral hilum was positive on preoperative PET in 107 patients. The median number of N1 lymph nodes sampled was 4 (range, 1-31). Positive ipsilateral N1 lymph nodes were identified pathologically in 91 patients (19%). Among the 91 patients with involved N1 lymph nodes, 40 were PET positive resulting in a sensitivity of 44%. Among 393 patients without pathologic involvement of hilar lymph nodes, 326 were PET negative resulting in a specificity of 83%. The positive predictive and negative predictive values were 37% and 86%, respectively.Positron emission tomography appears to have limitations in staging the ipsilateral hilar lymph nodes. Invasive sampling is appropriate if treatment would differ based on the nodal status.

Authors
Pepek, JM; Marks, LB; Berry, MF; Ready, NE; Gee, NG; Coleman, RE; D'Amico, TA; Crawford, J; Kelsey, CR
MLA Citation
Pepek, JM, Marks, LB, Berry, MF, Ready, NE, Gee, NG, Coleman, RE, D'Amico, TA, Crawford, J, and Kelsey, CR. "Accuracy of positron emission tomography in identifying hilar (N1) lymph node involvement in non-small cell lung cancer: Implications for stereotactic body radiation therapy." Practical radiation oncology 5.2 (March 2015): 79-84.
PMID
25413417
Source
epmc
Published In
Practical Radiation Oncology
Volume
5
Issue
2
Publish Date
2015
Start Page
79
End Page
84
DOI
10.1016/j.prro.2014.05.002

A review of relative dose intensity and survival in patients with metastatic solid tumors.

Studies have shown that in the curative setting patients with cancer receiving chemotherapy at higher relative dose intensity (RDI) had better clinical outcomes than those receiving treatment at lower RDI. However, the impact of RDI in advanced/metastatic disease remains unclear. A review of the literature was performed to evaluate the relationship between RDI and survival in patients with metastatic lung, breast, or ovarian cancer receiving chemotherapy. Few studies attempted to specifically associate RDI with survival in a systematic way. Findings from studies that analyzed overall survival with a prespecified RDI threshold support the emerging perception that maintaining an RDI≥85% has a favorable impact on survival. Nonetheless, these studies were limited by their retrospective nature. More studies are needed to further evaluate the impact of maintaining planned chemotherapy dose intensity on outcomes in metastatic solid tumors.

Authors
Havrilesky, LJ; Reiner, M; Morrow, PK; Watson, H; Crawford, J
MLA Citation
Havrilesky, LJ, Reiner, M, Morrow, PK, Watson, H, and Crawford, J. "A review of relative dose intensity and survival in patients with metastatic solid tumors." Critical reviews in oncology/hematology 93.3 (March 2015): 203-210.
PMID
25459671
Source
epmc
Published In
Critical Reviews in Oncology/Hematology
Volume
93
Issue
3
Publish Date
2015
Start Page
203
End Page
210
DOI
10.1016/j.critrevonc.2014.10.006

A review of relative dose intensity and survival in patients with metastatic solid tumors

© 2014 .Studies have shown that in the curative setting patients with cancer receiving chemotherapy at higher relative dose intensity (RDI) had better clinical outcomes than those receiving treatment at lower RDI. However, the impact of RDI in advanced/metastatic disease remains unclear. A review of the literature was performed to evaluate the relationship between RDI and survival in patients with metastatic lung, breast, or ovarian cancer receiving chemotherapy. Few studies attempted to specifically associate RDI with survival in a systematic way. Findings from studies that analyzed overall survival with a prespecified RDI threshold support the emerging perception that maintaining an RDI. ≥. 85% has a favorable impact on survival. Nonetheless, these studies were limited by their retrospective nature. More studies are needed to further evaluate the impact of maintaining planned chemotherapy dose intensity on outcomes in metastatic solid tumors.

Authors
Havrilesky, LJ; Reiner, M; Morrow, PK; Watson, H; Crawford, J
MLA Citation
Havrilesky, LJ, Reiner, M, Morrow, PK, Watson, H, and Crawford, J. "A review of relative dose intensity and survival in patients with metastatic solid tumors." Critical Reviews in Oncology/Hematology 93.3 (January 1, 2015): 203-210. (Review)
Source
scopus
Published In
Critical Reviews in Oncology/Hematology
Volume
93
Issue
3
Publish Date
2015
Start Page
203
End Page
210
DOI
10.1016/j.critrevonc.2014.10.006

The impact of chemotherapy dose intensity and supportive care on the risk of febrile neutropenia in patients with early stage breast cancer: a prospective cohort study.

BACKGROUND: Febrile neutropenia (FN) is a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. This study evaluated the time course of neutropenic events and patterns of supportive care interventions in patients receiving chemotherapy for early-stage breast cancer treated in oncology community practices. METHODS: A prospective cohort study of adult cancer patients initiating a new chemotherapy regimen was conducted at 115 US sites. Toxicity associated with chemotherapy including neutropenic and infectious complications was recorded over four cycles. Clinical interventions were recorded including reductions in chemotherapy dose intensity and use of supportive care measures. RESULTS: A total of 1,202 patients with stage I-III breast cancer were evaluated. The majority of neutropenic (116 of 196) and infection events (179 of 325) occurred in the initial cycle. A decrease in occurrence of FN and infection was observed in the subsequent cycles, along with an increase in utilization of colony stimulating factors (CSFs), antibiotics and reductions in chemotherapy dose intensity. The overall risk of FN in all patients was 16.3%. In patients who started treatment at or near full dose intensity, the FN risk reached 21.0% without primary CSF prophylaxis and it was 9.0% with prophylaxis. There was no significant difference in FN rates by menopausal or hormone receptors status. CONCLUSIONS: The risk of neutropenic complications is greatest in the initial cycle when most patients receive full-dose chemotherapy. A decrease in neutropenic events during subsequent cycles is associated with reduced dose intensity or increased use of supportive care measures. However, the cumulative risk of FN remains high in patients with early-stage breast cancer receiving full dose chemotherapy without prophylactic measures.

Authors
Culakova, E; Poniewierski, MS; Wolff, DA; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Culakova, E, Poniewierski, MS, Wolff, DA, Dale, DC, Crawford, J, and Lyman, GH. "The impact of chemotherapy dose intensity and supportive care on the risk of febrile neutropenia in patients with early stage breast cancer: a prospective cohort study." SpringerPlus 4 (January 2015): 396-.
PMID
26251780
Source
epmc
Published In
SpringerPlus
Volume
4
Publish Date
2015
Start Page
396
DOI
10.1186/s40064-015-1165-6

Impact of Comorbidities on Length of Stay and Mortality in Hospitalized Patients with Cancer and Febrile Neutropenia

Authors
Culakova, E; Poniewierski, MS; Crawford, J; Dale, DC; Lyman, GH
MLA Citation
Culakova, E, Poniewierski, MS, Crawford, J, Dale, DC, and Lyman, GH. "Impact of Comorbidities on Length of Stay and Mortality in Hospitalized Patients with Cancer and Febrile Neutropenia." BLOOD 124.21 (December 6, 2014).
Source
wos-lite
Published In
Blood
Volume
124
Issue
21
Publish Date
2014

Blood utilization and hemoglobin levels in cancer patients after label and coverage changes for erythropoiesis-stimulating agents.

A comprehensive literature search was performed to examine the influence of changes in erythropoietin-stimulating agent (ESA) label and reimbursement policies on utilization of red blood cell transfusions and patient hemoglobin levels in US cancer patients receiving chemotherapy or anemia management. Studies conducted in ESA-treated patients showed an increase in transfusion rates when comparing the post-intervention period with pre-intervention period (range of relative change: 15-125%). Results from studies conducted in patients receiving chemotherapy irrespective of anemia treatment were variable; single-institution-based studies tended to show a decrease in transfusion rates (range of relative change: -3.2 to -24.1%), while multiple-institution-based studies suggested an increase in transfusion rates (range of relative change: 12-182%). Studies showed decreases in hemoglobin levels during chemotherapy or at ESA initiation, and decreased ESA utilization.

Authors
Xu, H; Kaye, JA; Saltus, CW; Crawford, J; Gasal, E; Goodnough, LT
MLA Citation
Xu, H, Kaye, JA, Saltus, CW, Crawford, J, Gasal, E, and Goodnough, LT. "Blood utilization and hemoglobin levels in cancer patients after label and coverage changes for erythropoiesis-stimulating agents." Expert review of hematology 7.5 (October 2014): 617-633.
PMID
25081548
Source
epmc
Published In
Expert Review of Hematology
Volume
7
Issue
5
Publish Date
2014
Start Page
617
End Page
633
DOI
10.1586/17474086.2014.943730

Tumor acquisition for biomarker research in lung cancer.

The biopsy collection data from two lung cancer trials that required fresh tumor samples be obtained for microarray analysis were reviewed. In the trial for advanced disease, microarray data were obtained on 50 patient samples, giving an overall success rate of 60.2%. The majority of the specimens were obtained through CT-guided lung biopsies (N = 30). In the trial for early-stage patients, 28 tissue specimens were collected from excess tumor after surgical resection with a success rate of 85.7%. This tissue procurement program documents the feasibility in obtaining fresh tumor specimens prospectively that could be used for molecular testing.

Authors
Stevenson, M; Christensen, J; Shoemaker, D; Foster, T; Barry, WT; Tong, BC; Wahidi, M; Shofer, S; Datto, M; Ginsburg, G; Crawford, J; D'Amico, T; Ready, N
MLA Citation
Stevenson, M, Christensen, J, Shoemaker, D, Foster, T, Barry, WT, Tong, BC, Wahidi, M, Shofer, S, Datto, M, Ginsburg, G, Crawford, J, D'Amico, T, and Ready, N. "Tumor acquisition for biomarker research in lung cancer." Cancer investigation 32.6 (July 2014): 291-298.
PMID
24810245
Source
epmc
Published In
Cancer Investigation (Informa)
Volume
32
Issue
6
Publish Date
2014
Start Page
291
End Page
298
DOI
10.3109/07357907.2014.911880

Treatment strategies for myeloid growth factors and intravenous iron: when, what, and how?

Myeloid growth factors can reduce the risk of chemotherapy-induced neutropenia (CIN) and thus impact the survival of patients with cancer. Patients should be assessed for risk, taking into consideration patient-related risk factors and chemotherapy regimens. Patients stratified as having at least a 20% risk for CIN should be considered for prophylactic growth factors. The NCCN Guidelines for Myeloid Growth Factors provide category 1 recommendations for the daily use of filgrastim, tbo-filgrastim, and pegfilgrastim. Cancer-related anemia can be treated with erythropoiesis-stimulating agents, red blood cell transfusion, or intravenous iron.

Authors
Crawford, J; Rodgers, GM
MLA Citation
Crawford, J, and Rodgers, GM. "Treatment strategies for myeloid growth factors and intravenous iron: when, what, and how?." Journal of the National Comprehensive Cancer Network : JNCCN 12.5 Suppl (May 2014): 821-824.
PMID
24853225
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
12
Issue
5 Suppl
Publish Date
2014
Start Page
821
End Page
824

Patterns of chemotherapy-associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study.

Neutropenic complications remain an important dose-limiting toxicity of cancer chemotherapy-associated with considerable morbidity, mortality, and cost. Risk of the initial neutropenic event is greatest during the first cycle. The purpose of this study was to better understand timing of neutropenic events in relation to delivered chemotherapy dose intensity and utilization of supportive care during cancer treatment. A prospective cohort study of adult patients with solid tumors or lymphoma initiating chemotherapy was conducted at 115 randomly selected US practice sites between 2002 and 2006. Chemotherapy-associated toxicities were captured in up to four treatment cycles including severe neutropenia, febrile neutropenia, and infection. Documented interventions included colony-stimulating factor (CSF), antibiotics use, and reductions in chemotherapy relative dose intensity (RDI). A total of 3638 patients with breast (39.7%), lung (23.7%), colorectal (13.6%), ovarian (8.3%) cancers, or lymphoma (14.7%) were eligible for this analysis. The majority of neutropenic and infection events occurred in the first cycle. A significant inverse relationship was observed between reductions in neutropenic and infectious events and increased utilization of measures to reduce these complications in subsequent cycles. More than 60% of patients with stage IV solid tumors underwent reductions in RDI. Patients with lymphoma and stage I-III solid tumors had less dose reductions while receiving more prophylactic CSFs. Approximately, 15% of patients received prophylactic antibiotics. While the risk of neutropenic complications remains greatest during the initial cycle of chemotherapy, subsequently instituted clinical measures in efforts to reduce the risk of these events vary with cancer type and stage.

Authors
Culakova, E; Thota, R; Poniewierski, MS; Kuderer, NM; Wogu, AF; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Culakova, E, Thota, R, Poniewierski, MS, Kuderer, NM, Wogu, AF, Dale, DC, Crawford, J, and Lyman, GH. "Patterns of chemotherapy-associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study." Cancer medicine 3.2 (April 2014): 434-444.
PMID
24706592
Source
epmc
Published In
Cancer Medicine
Volume
3
Issue
2
Publish Date
2014
Start Page
434
End Page
444
DOI
10.1002/cam4.200

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70Gy daily radiotherapy: CALGB 30904

Introduction: Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70. Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Methods: Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70. Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3-5 pulmonary toxicities after concurrent chemoradiotherapy. Results: 100 patients were included. No patient experienced grade 4-5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p= 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p= 0.05).). Furthermore, exposure of larger volumes of lung to lower (median V5. = 70%, p= 0.09, median V10. = 63%, p= 0.07), intermediate (median V20. = 50, p= 0.04) and high (median V60. = 25%, p= 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose (median 31. Gy) p= 0.019. Conclusion: Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation. © 2013 Elsevier Ireland Ltd.

Authors
Salama, JK; Pang, H; Bogart, JA; Blackstock, AW; Urbanic, JJ; Hodgson, L; Crawford, J; Vokes, EE
MLA Citation
Salama, JK, Pang, H, Bogart, JA, Blackstock, AW, Urbanic, JJ, Hodgson, L, Crawford, J, and Vokes, EE. "Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70Gy daily radiotherapy: CALGB 30904." Lung Cancer 82.3 (December 1, 2013): 436-440.
Source
scopus
Published In
Lung Cancer
Volume
82
Issue
3
Publish Date
2013
Start Page
436
End Page
440
DOI
10.1016/j.lungcan.2013.10.001

A Phase 2 Randomized Trial of Paclitaxel and Carboplatin with or without Panitumumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer

Authors
Crawford, J; Swanson, P; Schwarzenberger, P; Sandler, A; Prager, D; Zhang, K; Freeman, DJ; Johnson, CW; Krishnan, K; Johnson, D
MLA Citation
Crawford, J, Swanson, P, Schwarzenberger, P, Sandler, A, Prager, D, Zhang, K, Freeman, DJ, Johnson, CW, Krishnan, K, and Johnson, D. "A Phase 2 Randomized Trial of Paclitaxel and Carboplatin with or without Panitumumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer." JOURNAL OF THORACIC ONCOLOGY 8.12 (December 2013): 1510-1518.
PMID
24389433
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
8
Issue
12
Publish Date
2013
Start Page
1510
End Page
1518
DOI
10.1097/JTO.0b013e3182a7d1da

Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial)

Authors
Ramalingam, S; Crawford, J; Chang, A; Manegold, C; Perez-Soler, R; Douillard, J-Y; Thatcher, N; Barlesi, F; Owonikoko, T; Wang, Y; Pultar, P; Zhu, J; Malik, R; Giaccone, G; Investigators, FORTIS-MS
MLA Citation
Ramalingam, S, Crawford, J, Chang, A, Manegold, C, Perez-Soler, R, Douillard, J-Y, Thatcher, N, Barlesi, F, Owonikoko, T, Wang, Y, Pultar, P, Zhu, J, Malik, R, Giaccone, G, and Investigators, FORTIS-MS. "Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial)." ANNALS OF ONCOLOGY 24.11 (November 2013): 2875-2880.
PMID
24050956
Source
wos-lite
Published In
Annals of Oncology
Volume
24
Issue
11
Publish Date
2013
Start Page
2875
End Page
2880
DOI
10.1093/annonc/mdt371

Moving Forward With Myeloid Growth Factors

Authors
Crawford, J
MLA Citation
Crawford, J. "Moving Forward With Myeloid Growth Factors." JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK 11.10 (October 2013): 1181-1182.
PMID
24142818
Source
wos-lite
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
10
Publish Date
2013
Start Page
1181
End Page
1182

The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The granulocyte colony-stimulating factor (G-CSF) is utilized to reduce neutropenic complications in patients receiving cancer chemotherapy. This study represents a systematic review and evidence summary of the impact of G-CSF support on chemotherapy dose intensity and overall mortality. MATERIALS AND METHODS: All randomized controlled trials (RCTs) comparing chemotherapy with or without G-CSF support and reporting all-cause mortality with at least 2 years of follow-up were sought. Dual-blind data abstraction of disease, treatment, patient and outcome study results with conflict resolution by third party was carried out. RESULTS: The search revealed 61 randomized comparisons of chemotherapy with or without initial G-CSF support. Death was reported in 4251 patients randomized to G-CSFs and in 5188 controls. Relative risk (RR) with G-CSF support for all-cause mortality was 0.93 (95% confidence interval: 0.90-0.96; P < 0.001). RR for mortality varied by intended chemotherapy dose and schedule: same dose and schedule (RR = 0.96; P = 0.060), dose dense (RR = 0.89; P < 0.001), dose escalation (RR = 0.92; P = 0.019) and drug substitution or addition (RR = 0.94; P = 0.003). Greater RR reduction was observed among studies with longer follow-up (P = 0.02), where treatment was for curative intent (RR = 0.91; P < 0.001), and where survival was the primary outcome (RR = 0.91; P < 0.001). CONCLUSIONS: All-cause mortality is reduced in patients receiving chemotherapy with primary G-CSF support. The greatest impact was observed in RCTs in patients receiving dose-dense schedules.

Authors
Lyman, GH; Dale, DC; Culakova, E; Poniewierski, MS; Wolff, DA; Kuderer, NM; Huang, M; Crawford, J
MLA Citation
Lyman, GH, Dale, DC, Culakova, E, Poniewierski, MS, Wolff, DA, Kuderer, NM, Huang, M, and Crawford, J. "The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials." Ann Oncol 24.10 (October 2013): 2475-2484. (Review)
PMID
23788754
Source
pubmed
Published In
Annals of Oncology
Volume
24
Issue
10
Publish Date
2013
Start Page
2475
End Page
2484
DOI
10.1093/annonc/mdt226

Myeloid Growth Factors

Authors
Crawford, J; Armitage, J; Balducci, L; Becker, PS; Blayney, DW; Cataland, SR; Heaney, ML; Hudock, S; Kloth, DD; Kuter, DJ; Lyman, GH; McMahon, B; Rugo, HS; Saad, AA; Schwartzberg, LS; Shayani, S; Steensma, DP; Talbott, M; Vadhan-Raj, S; Westervelt, P; Westmoreland, M; Dwyer, M; Ho, M
MLA Citation
Crawford, J, Armitage, J, Balducci, L, Becker, PS, Blayney, DW, Cataland, SR, Heaney, ML, Hudock, S, Kloth, DD, Kuter, DJ, Lyman, GH, McMahon, B, Rugo, HS, Saad, AA, Schwartzberg, LS, Shayani, S, Steensma, DP, Talbott, M, Vadhan-Raj, S, Westervelt, P, Westmoreland, M, Dwyer, M, and Ho, M. "Myeloid Growth Factors." JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK 11.10 (October 2013): 1266-1290.
PMID
24142827
Source
wos-lite
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
10
Publish Date
2013
Start Page
1266
End Page
1290

Prevention and treatment of chemotherapy-induced neutropenia

Authors
Crawford, J; Barth Geller, G
MLA Citation
Crawford, J, and Barth Geller, G. "Prevention and treatment of chemotherapy-induced neutropenia." Clinical Advances in Hematology and Oncology 11.8 (August 1, 2013): 514-517.
PMID
24518423
Source
scopus
Published In
Clinical advances in hematology & oncology : H&O
Volume
11
Issue
8
Publish Date
2013
Start Page
514
End Page
517

A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

INTRODUCTION: Standard therapy for limited-stage small-cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy (RT) followed by prophylactic cranial radiotherapy. Although many consider the standard RT regimen to be 45 Gy in 1.5 Gy twice-daily fractions, this has failed to gain widespread acceptance. We pooled data of patients assigned to receive daily RT of 70 Gy from three, consecutive prospective Cancer and Leukemia Group B L-SCLC cancer trials and report the results here. METHODS: All patients from consecutive Cancer and Leukemia Group B L-SCLC trials (39808, 30002, and 30206) using high-dosage daily RT with concurrent chemotherapy were included, and analyzed for toxicity, disease control, and survival. Overall survival (OS) and progression-free survival (PFS) were modeled using Cox proportional hazards models. Prognostic variables for OS-rate and PFS-rate were assessed using logistic regression model. RESULTS: Two hundred patients were included. The median follow-up was 78 months. Grade 3 or greater esophagitis was 23%. The median OS for pooled population was 19.9 months (95% confidence interval [CI]: 16.7-22.3), and 5-year OS rate was 20% (95% CI: 16-27%). The 2-year PFS was 26% (95% CI: 21-32%). Multivariate analysis found younger age (p = 0.02; hazard ratio [HR]: 1.023; 95% CI: 21-32), and female sex (p = 0.02; HR:0.69; 95% CI: 0.50-0.94) independently associated with improved overall survival. CONCLUSION: Two-Gy daily RT to a total dosage of 70 Gy was well tolerated with similar survival to 45 Gy (1.5 Gy twice-daily). This experience may aid practitioners decide whether high-dosage daily RT with platinum-based chemotherapy is appropriate outside of a clinical trial.

Authors
Salama, JK; Hodgson, L; Pang, H; Urbanic, JJ; Blackstock, AW; Schild, SE; Crawford, J; Bogart, JA; Vokes, EE; Cancer and Leukemia Group B,
MLA Citation
Salama, JK, Hodgson, L, Pang, H, Urbanic, JJ, Blackstock, AW, Schild, SE, Crawford, J, Bogart, JA, Vokes, EE, and Cancer and Leukemia Group B, . "A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904." J Thorac Oncol 8.8 (August 2013): 1043-1049.
PMID
23715301
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
8
Issue
8
Publish Date
2013
Start Page
1043
End Page
1049
DOI
10.1097/JTO.0b013e318293d8a4

A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting.

Early-stage breast cancer (ESBC) is commonly treated with myelosuppressive chemotherapy, and maintaining full-dose chemotherapy on the planned schedule is associated with improved patient outcome. Retrospective analysis of patients with ESBC treated from 1997 to 2000 showed that 56 % of patients received a relative dose intensity (RDI) <85 % (Lyman et al., J Clin Oncol 21(24):4524-4531, 2003). To determine current practice, we evaluated treatment patterns at 24 US community- and hospital-based oncology practices, 79 % of which participated in the previous study. Data were abstracted from medical records of 532 patients with surgically resected ESBC (stage I-IIIa) treated from 2007 to 2009, who were ≥18 years old and had completed ≥1 cycle of one of the following regimens: docetaxel + cyclophosphamide (TC); doxorubicin + cyclophosphamide (AC); AC followed by paclitaxel (AC-T); docetaxel + carboplatin + trastuzumab (TCH); or docetaxel + doxorubicin + cyclophosphamide (TAC). Endpoints included RDI, dose delays, dose reductions, grade 3/4 neutropenia, febrile neutropenia (FN), FN-related hospitalization, granulocyte colony-stimulating factor (G-CSF) use, and antimicrobial use. In this study, TC was the most common chemotherapy regimen (42 %), and taxane-based chemotherapy regimens were more common relative to the previously published results (89 vs <4 %). Overall, 83.8 % of patients received an RDI ≥85 %, an improvement over the previous study where 44.5 % received an RDI ≥85 %. Other changes seen between this and the previous study included a lower incidence of dose delays (16 vs 25 %) and dose reductions (21 vs 37 %) and increased use of primary prophylactic G-CSF (76 vs ~3 %). Here, 40 % of patients had grade 3/4 neutropenia, 3 % had FN, 2 % had an FN-related hospitalization, and 30 % received antimicrobial therapy; these measures were not available in the previously published results. Though RDI was higher here than in the previous study, 16.2 % of patients still received an RDI <85 %. Understanding factors that contribute to reduced RDI may further improve chemotherapy delivery, and ultimately, patient outcomes.

Authors
Lyman, GH; Dale, DC; Tomita, D; Whittaker, S; Crawford, J
MLA Citation
Lyman, GH, Dale, DC, Tomita, D, Whittaker, S, and Crawford, J. "A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting." Breast Cancer Res Treat 139.3 (June 2013): 863-872.
PMID
23771731
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
139
Issue
3
Publish Date
2013
Start Page
863
End Page
872
DOI
10.1007/s10549-013-2582-2

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

Background: The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods: We analysed individual patients' data from 15 071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings: In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ2=0·83, 95% CI 0·83-0·83 in trials without radiotherapy, and 0·87, 0·87-0·87 in trials with radiotherapy) and excellent at trial level (R 2=0·92, 95% CI 0·88-0·95 in trials without radiotherapy and 0·99, 0·98-1·00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ2 range 0·77-0·85, dependent on the regimen being assessed) and trial level (R 2 range 0·89-0·97). In studies with data on locoregional control, individual-level correlations were good (ρ2=0·71, 95% CI 0·71-0·71 for concurrent chemotherapy and ρ2=0·61, 0·61-0·61 for modified vs standard radiotherapy) and trial-level correlations very good (R 2=0·85, 95% CI 0·77-0·92 for concurrent chemotherapy and R 2=0·95, 0·91-0·98 for modified vs standard radiotherapy). Interpretation: We found a high level of evidence that DFS is a valid surrogate endpoint for overall survival in studies of adjuvant chemotherapy involving patients with non-small-cell lung cancers, and PFS in those of chemotherapy and radiotherapy for patients with locally advanced lung cancers. Extrapolation to targeted agents, however, is not automatically warranted. Funding: Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, British Medical Research Council, Sanofi-Aventis. © 2013 Elsevier Ltd. All rights reserved.

Authors
Mauguen, A; Pignon, J-P; Burdett, S; Domerg, C; Fisher, D; Paulus, R; Mandrekar, SJ; Belani, CP; Shepherd, FA; Eisen, T; al, E
MLA Citation
Mauguen, A, Pignon, J-P, Burdett, S, Domerg, C, Fisher, D, Paulus, R, Mandrekar, SJ, Belani, CP, Shepherd, FA, Eisen, T, and al, E. "Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data." The Lancet Oncology (2013).
PMID
23680111
Source
scival
Published In
The Lancet Oncology
Publish Date
2013
DOI
10.1016/S1470-2045(13)70158-X

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: A re-analysis of meta-analyses of individual patients' data

Background: The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels. Methods: We analysed individual patients' data from 15 071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints. Findings: In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (ρ2=0·83, 95% CI 0·83-0·83 in trials without radiotherapy, and 0·87, 0·87-0·87 in trials with radiotherapy) and excellent at trial level (R2=0·92, 95% CI 0·88-0·95 in trials without radiotherapy and 0·99, 0·98-1·00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (ρ2 range 0·77-0·85, dependent on the regimen being assessed) and trial level (R2 range 0·89-0·97). In studies with data on locoregional control, individual-level correlations were good (ρ2=0·71, 95% CI 0·71-0·71 for concurrent chemotherapy and ρ2=0·61, 0·61-0·61 for modified vs standard radiotherapy) and trial-level correlations very good (R2=0·85, 95% CI 0·77-0·92 for concurrent chemotherapy and R2=0·95, 0·91-0·98 for modified vs standard radiotherapy). Interpretation: We found a high level of evidence that DFS is a valid surrogate endpoint for overall survival in studies of adjuvant chemotherapy involving patients with non-small-cell lung cancers, and PFS in those of chemotherapy and radiotherapy for patients with locally advanced lung cancers. Extrapolation to targeted agents, however, is not automatically warranted. Funding: Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, British Medical Research Council, Sanofi-Aventis. © 2013 Elsevier Ltd.

Authors
Mauguen, A; Pignon, JP; Burdett, S; Domerg, C; Fisher, D; Paulus, R; Mandrekar, SJ; Belani, CP; Shepherd, FA; Eisen, T; Pang, H; Collette, L; Sause, WT; Dahlberg, SE; Crawford, J; O'Brien, M; Schild, SE; Parmar, M; Tierney, JF; Pechoux, CL; Michiels, S
MLA Citation
Mauguen, A, Pignon, JP, Burdett, S, Domerg, C, Fisher, D, Paulus, R, Mandrekar, SJ, Belani, CP, Shepherd, FA, Eisen, T, Pang, H, Collette, L, Sause, WT, Dahlberg, SE, Crawford, J, O'Brien, M, Schild, SE, Parmar, M, Tierney, JF, Pechoux, CL, and Michiels, S. "Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: A re-analysis of meta-analyses of individual patients' data." The Lancet Oncology 14.7 (2013): 619-626.
Source
scival
Published In
The Lancet Oncology
Volume
14
Issue
7
Publish Date
2013
Start Page
619
End Page
626
DOI
10.1016/S1470-2045(13)70158-X

A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting

Early-stage breast cancer (ESBC) is commonly treated with myelosuppressive chemotherapy, and maintaining full-dose chemotherapy on the planned schedule is associated with improved patient outcome. Retrospective analysis of patients with ESBC treated from 1997 to 2000 showed that 56 % of patients received a relative dose intensity (RDI) <85 % (Lyman et al., J Clin Oncol 21(24):4524-4531, 2003). To determine current practice, we evaluated treatment patterns at 24 US community- and hospital-based oncology practices, 79 % of which participated in the previous study. Data were abstracted from medical records of 532 patients with surgically resected ESBC (stage I-IIIa) treated from 2007 to 2009, who were ≥18 years old and had completed ≥1 cycle of one of the following regimens: docetaxel + cyclophosphamide (TC); doxorubicin + cyclophosphamide (AC); AC followed by paclitaxel (AC-T); docetaxel + carboplatin + trastuzumab (TCH); or docetaxel + doxorubicin + cyclophosphamide (TAC). Endpoints included RDI, dose delays, dose reductions, grade 3/4 neutropenia, febrile neutropenia (FN), FN-related hospitalization, granulocyte colony-stimulating factor (G-CSF) use, and antimicrobial use. In this study, TC was the most common chemotherapy regimen (42 %), and taxane-based chemotherapy regimens were more common relative to the previously published results (89 vs <4 %). Overall, 83.8 % of patients received an RDI ≥85 %, an improvement over the previous study where 44.5 % received an RDI ≥85 %. Other changes seen between this and the previous study included a lower incidence of dose delays (16 vs 25 %) and dose reductions (21 vs 37 %) and increased use of primary prophylactic G-CSF (76 vs ~3 %). Here, 40 % of patients had grade 3/4 neutropenia, 3 % had FN, 2 % had an FN-related hospitalization, and 30 % received antimicrobial therapy; these measures were not available in the previously published results. Though RDI was higher here than in the previous study, 16.2 % of patients still received an RDI <85 %. Understanding factors that contribute to reduced RDI may further improve chemotherapy delivery, and ultimately, patient outcomes. © 2013 Springer Science+Business Media New York.

Authors
Lyman, GH; Dale, DC; Tomita, D; Whittaker, S; Crawford, J
MLA Citation
Lyman, GH, Dale, DC, Tomita, D, Whittaker, S, and Crawford, J. "A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting." Breast Cancer Research and Treatment 139.3 (2013): 863-872.
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
139
Issue
3
Publish Date
2013
Start Page
863
End Page
872
DOI
10.1007/s10549-013-2582-2

A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904

INTRODUCTION: Standard therapy for limited-stage small-cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy (RT) followed by prophylactic cranial radiotherapy. Although many consider the standard RT regimen to be 45 Gy in 1.5 Gy twice-daily fractions, this has failed to gain widespread acceptance. We pooled data of patients assigned to receive daily RT of 70 Gy from three, consecutive prospective Cancer and Leukemia Group B L-SCLC cancer trials and report the results here. METHODS: All patients from consecutive Cancer and Leukemia Group B L-SCLC trials (39808, 30002, and 30206) using high-dosage daily RT with concurrent chemotherapy were included, and analyzed for toxicity, disease control, and survival. Overall survival (OS) and progression-free survival (PFS) were modeled using Cox proportional hazards models. Prognostic variables for OS-rate and PFS-rate were assessed using logistic regression model. RESULTS: Two hundred patients were included. The median follow-up was 78 months. Grade 3 or greater esophagitis was 23%. The median OS for pooled population was 19.9 months (95% confidence interval [CI]: 16.7-22.3), and 5-year OS rate was 20% (95% CI: 16-27%). The 2-year PFS was 26% (95% CI: 21-32%). Multivariate analysis found younger age (p = 0.02; hazard ratio [HR]: 1.023; 95% CI: 21-32), and female sex (p = 0.02; HR:0.69; 95% CI: 0.50-0.94) independently associated with improved overall survival. CONCLUSION: Two-Gy daily RT to a total dosage of 70 Gy was well tolerated with similar survival to 45 Gy (1.5 Gy twice-daily). This experience may aid practitioners decide whether high-dosage daily RT with platinum-based chemotherapy is appropriate outside of a clinical trial. © 2013 by the International Association for the Study of Lung Cancer.

Authors
Salama, JK; Hodgson, L; Pang, H; Urbanic, JJ; Blackstock, AW; Schild, SE; Crawford, J; Bogart, JA; Vokes, EE
MLA Citation
Salama, JK, Hodgson, L, Pang, H, Urbanic, JJ, Blackstock, AW, Schild, SE, Crawford, J, Bogart, JA, and Vokes, EE. "A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904." Journal of Thoracic Oncology 8.8 (2013): 1043-1049.
Source
scival
Published In
Journal of Thoracic Oncology
Volume
8
Issue
8
Publish Date
2013
Start Page
1043
End Page
1049
DOI
10.1097/JTO.0b013e318293d8a4

Risk factors for in-hospital mortality and prolonged length of stay in older patients with solid tumor malignancies

Objective: Hospitalized adult patients with cancer and with major comorbidities have higher mortality rates and longer duration of hospitalization. There is limited understanding of risk factors that contribute to prolonged hospitalization and mortality in older patients with solid tumors. Materials and Methods: Risk factors associated with in-hospital mortality and prolonged length of stay (LOS) in older patients with cancer were investigated in a retrospective cohort study. Data from the University HealthSystem Consortium database included 386,377 patients age ≥ 65 years with solid tumors hospitalized between 1995 and 2003 at 133 U.S. academic medical centers. Results: The overall mortality rate was 7.3%. Mortality in older patients with cancer was strongly associated with longer LOS. Almost twice as many deaths were observed among those with LOS ≥ 10 days (p < .0001). Nearly 38% of older cancer patients who died in hospital had potentially curable disease. Primary central nervous system malignancies were most strongly associated with in-hospital mortality (OR = 1.81; 1.59-2.07), followed by esophageal (OR = 1.74; 1.54-1.97) and lung cancer (OR = 1.57; 1.43-1.72). Male gender, African-American race, and Hispanic and Asian race/ethnicity were associated with increased risk of mortality (p < 0.0001). Additional risk factors included metastatic disease, infection, neutropenia, renal, lung, hepatic, cerebrovascular disease, arterial/venous thromboembolism, heart failure, and red blood cell transfusion. Risk factors for prolonged LOS included gastric cancer, infection, venous thromboembolism and red blood cell transfusion. Conclusions: Prolonged LOS was strongly associated with mortality. Risk factors such as infection, neutropenia and red blood cell transfusion, when modified, could potentially reduce rates of prolonged LOS and mortality in older patients with cancer. © 2013 Elsevier Inc. All rights reserved.

Authors
Shayne, M; Culakova, E; Poniewierski, MS; Dale, DC; Crawford, J; Wogu, AF; Lyman, GH
MLA Citation
Shayne, M, Culakova, E, Poniewierski, MS, Dale, DC, Crawford, J, Wogu, AF, and Lyman, GH. "Risk factors for in-hospital mortality and prolonged length of stay in older patients with solid tumor malignancies." Journal of Geriatric Oncology (2013).
PMID
24472473
Source
scival
Published In
Journal of Geriatric Oncology
Publish Date
2013
DOI
10.1016/j.jgo.2013.05.005

Risk factors for in-hospital mortality and prolonged length of stay in older patients with solid tumor malignancies

Objective: Hospitalized adult patients with cancer and with major comorbidities have higher mortality rates and longer duration of hospitalization. There is limited understanding of risk factors that contribute to prolonged hospitalization and mortality in older patients with solid tumors. Materials and Methods: Risk factors associated with in-hospital mortality and prolonged length of stay (LOS) in older patients with cancer were investigated in a retrospective cohort study. Data from the University HealthSystem Consortium database included 386,377 patients age. ≥. 65. years with solid tumors hospitalized between 1995 and 2003 at 133 U.S. academic medical centers. Results: The overall mortality rate was 7.3%. Mortality in older patients with cancer was strongly associated with longer LOS. Almost twice as many deaths were observed among those with LOS. ≥. 10. days (p. <. 0.0001). Nearly 38% of older cancer patients who died in hospital had potentially curable disease. Primary central nervous system malignancies were most strongly associated with in-hospital mortality (OR. =. 1.81; 1.59-2.07), followed by esophageal (OR. =. 1.74; 1.54-1.97) and lung cancer (OR. =. 1.57; 1.43-1.72). Male gender, African-American race, and Hispanic and Asian race/ethnicity were associated with increased risk of mortality (p. <. 0.0001). Additional risk factors included metastatic disease, infection, neutropenia, renal, lung, hepatic, cerebrovascular disease, arterial/venous thromboembolism, heart failure, and red blood cell transfusion. Risk factors for prolonged LOS included gastric cancer, infection, venous thromboembolism and red blood cell transfusion. Conclusions: Prolonged LOS was strongly associated with mortality. Risk factors such as infection, neutropenia and red blood cell transfusion, when modified, could potentially reduce rates of prolonged LOS and mortality in older patients with cancer. © 2013 Elsevier Inc.

Authors
Shayne, M; Culakova, E; Poniewierski, MS; Dale, DC; Crawford, J; Wogu, AF; Lyman, GH
MLA Citation
Shayne, M, Culakova, E, Poniewierski, MS, Dale, DC, Crawford, J, Wogu, AF, and Lyman, GH. "Risk factors for in-hospital mortality and prolonged length of stay in older patients with solid tumor malignancies." Journal of Geriatric Oncology 4.4 (2013): 310-318.
Source
scival
Published In
Journal of Geriatric Oncology
Volume
4
Issue
4
Publish Date
2013
Start Page
310
End Page
318
DOI
10.1016/j.jgo.2013.05.005

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904

Authors
Salama, JK; Pang, H; Bogart, JA; Blackstock, AW; Urbanic, JJ; Hodgson, L; Crawford, J; Vokes, EE
MLA Citation
Salama, JK, Pang, H, Bogart, JA, Blackstock, AW, Urbanic, JJ, Hodgson, L, Crawford, J, and Vokes, EE. "Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904." Lung Cancer (2013).
PMID
24396884
Source
scopus
Published In
Lung Cancer
Publish Date
2013

Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multiagent chemotherapy for epithelial ovarian cancer.

OBJECTIVE: There is limited information concerning the role of relative dose intensity (RDI) on clinical outcomes in solid tumors. The objectives of our study were to evaluate the prognostic significance of RDI and predictors of reduced RDI in women with newly diagnosed advanced stage epithelial ovarian carcinoma (EOC) treated with platinum-based chemotherapy. METHODS: A multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy between 1995 and 2009 was conducted. Data were obtained to include the first four chemotherapy cycles administered. Outcomes included: (1) planned and delivered relative dose intensity (RDI), (2) progression-free (PFS) and overall (OS) survival. Survival estimates were based on Kaplan and Meier method, and multivariate analyses were based on logistic regression and Cox proportional hazards regression. RESULTS: Evaluable subjects included 325 women. With median follow-up of 34months (range, 0.4 - 170), progression or recurrence was recorded in 241 (73.9%) and death in 179 (54.9%). In multivariate analysis, predictors of reduced planned RDI were: treatment off research protocols (odds ratio [OR]=4.3; P2m(2) (OR=6.14; P

Authors
Hanna, RK; Poniewierski, MS; Laskey, RA; Lopez, MA; Shafer, A; Le, LV; Crawford, J; Dale, DC; Gehrig, PA; Secord, AA; Havrilesky, LJ; Lyman, GH
MLA Citation
Hanna, RK, Poniewierski, MS, Laskey, RA, Lopez, MA, Shafer, A, Le, LV, Crawford, J, Dale, DC, Gehrig, PA, Secord, AA, Havrilesky, LJ, and Lyman, GH. "Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multiagent chemotherapy for epithelial ovarian cancer." Gynecologic oncology (December 2012). (Academic Article)
PMID
23262376
Source
manual
Published In
Gynecologic Oncology
Publish Date
2012
DOI
10.1016/j.ygyno.2012.12.017

Retraction: characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.

Authors
Stevenson, M; Mostertz, W; Acharya, CR; Kim, W; Walters, K; Barry, W; Higgins, K; Tuchman, SA; Crawford, J; Vlahovic, G; Ready, N; Onaitis, M; Potti, A
MLA Citation
Stevenson, M, Mostertz, W, Acharya, CR, Kim, W, Walters, K, Barry, W, Higgins, K, Tuchman, SA, Crawford, J, Vlahovic, G, Ready, N, Onaitis, M, and Potti, A. "Retraction: characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma." Clin Cancer Res 18.6 (March 15, 2012): 1818-.
PMID
22355011
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
6
Publish Date
2012
Start Page
1818
DOI
10.1158/1078-0432.CCR-12-0337

Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial

Purpose: Erlotinib is clinically effective in patients with non-small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics. Patients and Methods: Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory. Results PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P = .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP. Conclusion Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit. © 2012 by American Society of Clinical Oncology.

Authors
Jänne, PA; Wang, X; Socinski, MA; Crawford, J; Stinchcombe, TE; Gu, L; Capelletti, M; Edelman, MJ; Villalona-Calero, MA; Kratzke, R; Vokes, EE; Miller, VA
MLA Citation
Jänne, PA, Wang, X, Socinski, MA, Crawford, J, Stinchcombe, TE, Gu, L, Capelletti, M, Edelman, MJ, Villalona-Calero, MA, Kratzke, R, Vokes, EE, and Miller, VA. "Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial." Journal of Clinical Oncology 30.17 (2012): 2063-2069.
PMID
22547605
Source
scival
Published In
Journal of Clinical Oncology
Volume
30
Issue
17
Publish Date
2012
Start Page
2063
End Page
2069
DOI
10.1200/JCO.2011.40.1315

Benefits and risks of using erythropoiesis-stimulating agents (ESAs) in lung cancer patients: Study-level and patient-level meta-analyses

In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate ESA benefits and risks in lung cancer, we conducted meta-analyses of data from controlled ESA trials conducted in lung cancer patients. Study-level analyses included controlled ESA trials reporting lung cancer mortality, identified from the 2006 Cochrane ESA report and from a systematic search for studies published through December 2010. Patient-level analyses included data from lung cancer patients receiving chemotherapy in Amgen studies evaluating darbepoetin alfa (DA) vs placebo. Study-level and patient-level analyses examined deaths, progression, and transfusion incidence. Patient-level analyses also examined adverse events (AEs) and fatigue. In a study-level meta-analysis of nine ESA studies of 2342 patients receiving chemotherapy, the ESA odds ratio (OR) was 0.87 (95% confidence interval [CI] 0.69-1.09) for mortality; the overall random-effects risk difference (95% CI) for mortality was -0.02 (-0.06, 0.02). The ESA OR (95% CI) for disease progression in five chemotherapy studies reporting progression was 0.84 (0.65-1.09). The ESA odds ratio (95% CI) was 0.34 (0.28-0.41) for transfusion incidence. In a patient-level meta-analysis of four studies evaluating 1009 patients through follow-up, the median survival time was 41 weeks with DA and 38 weeks with placebo. During the combined study and follow-up periods, 80% of placebo-group patients and 74% of DA patients died (mortality hazard ratio [HR] 0.90 [95% CI, 0.78-1.03] for DA); results were similar for small cell lung cancer and non-small cell lung cancer. Overall, 87% of placebo patients and 84% of DA patients progressed or died. Fewer DA patients had transfusions (week 5 through end-of-study, DA 19%, placebo 43%). AEs included thrombotic/embolic events (DA 10.5%, placebo 7.2%), cerebrovascular disorders (DA 3.7%, placebo 4.2%), pulmonary edema (DA 0.4%, placebo 1.0%) and pulmonary embolism (DA 1.8%, placebo 0.6%).These meta-analyses suggest that ESAs reduce transfusions without increasing mortality or disease progression in lung cancer patients undergoing chemotherapy. © 2012 Elsevier Ireland Ltd.

Authors
Vansteenkiste, J; Glaspy, J; Henry, D; Ludwig, H; Pirker, R; Tomita, D; Collins, H; Crawford, J
MLA Citation
Vansteenkiste, J, Glaspy, J, Henry, D, Ludwig, H, Pirker, R, Tomita, D, Collins, H, and Crawford, J. "Benefits and risks of using erythropoiesis-stimulating agents (ESAs) in lung cancer patients: Study-level and patient-level meta-analyses." Lung Cancer 76.3 (2012): 478-485.
PMID
22277104
Source
scival
Published In
Lung Cancer
Volume
76
Issue
3
Publish Date
2012
Start Page
478
End Page
485
DOI
10.1016/j.lungcan.2011.12.015

Third CECOG consensus on the systemic treatment of non-small-cell lung cancer

The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer-update 2004. Lung Cancer 2005; 50: 129-137). The principle of all CECOG consensus is such that evidence-based recommendations for state-of-the-art treatment are given upon which all participants and authors of the manuscript have to agree (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). This is of particular importance in diseases in which treatment options depend on very particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer-update 2004. Lung Cancer 2005; 50: 129-137; Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). Since the publication of the last CECOG consensus on the medical treatment of NSCLC, a series of diagnostic tools for the characterization of biomarkers for personalized therapy for NSCLC as well as therapeutic options including adjuvant treatment, targeted therapy, and maintenance treatment have emerged and strongly influenced the field. Thus, the present third consensus was generated that not only readdresses previous disease-related issues but also expands toward recent developments in the management of NSCLC. It is the aim of the present consensus to summarize minimal quality-oriented requirements for individual patients with NSCLC in its various stages based upon levels of evidence in the light of a rapidly expanding array of individual therapeutic options. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Authors
Brodowicz, T; Ciuleanu, T; Crawford, J; Filipits, M; Fischer, JR; Georgoulias, V; Gridelli, C; Hirsch, FR; Jassem, J; Kosmidis, P; Krzakowski, M; Manegold, C; Pujol, JL; Stahel, R; Thatcher, N; Vansteenkiste, J; Minichsdorfer, C; Zöchbauer-Müller, S; Pirker, R; Zielinski, CC
MLA Citation
Brodowicz, T, Ciuleanu, T, Crawford, J, Filipits, M, Fischer, JR, Georgoulias, V, Gridelli, C, Hirsch, FR, Jassem, J, Kosmidis, P, Krzakowski, M, Manegold, C, Pujol, JL, Stahel, R, Thatcher, N, Vansteenkiste, J, Minichsdorfer, C, Zöchbauer-Müller, S, Pirker, R, and Zielinski, CC. "Third CECOG consensus on the systemic treatment of non-small-cell lung cancer." Annals of Oncology 23.5 (2012): 1223-1229.
PMID
21940784
Source
scival
Published In
Annals of Oncology
Volume
23
Issue
5
Publish Date
2012
Start Page
1223
End Page
1229
DOI
10.1093/annonc/mdr381

Reporting of myelotoxicity associated with emerging regimens for the treatment of selected solid tumors

In this article, we reviewed and quantified reporting of the risk of myelotoxicity, specifically febrile neutropenia (FN), and the related use of supportive care with colony-stimulating factor (CSF) or antibiotics in clinical trials published between January 2005 and June 2009, evaluating emerging regimens for the treatment of selected solid tumors. Our analysis showed that clinically significant neutropenia and neutropenia-related events were generally described in the studies evaluated (grade 3/4 neutropenia incidence, 72%; FN incidence, 53%). However, use of CSF and antibiotics was infrequently and inconsistently reported (trials reporting prophylactic CSF and antibiotics use: in the methods section, 38% and 10%, respectively; in the results section, 19% and 1%, respectively). These results highlight the need for a standardized approach to reporting neutropenic outcomes and use of supportive care measures. This can assist clinicians in prospectively managing relevant toxicities associated with these emerging regimens and thereby facilitate their safe and effective use in clinical practice. © 2011 Elsevier Ireland Ltd.

Authors
Chan, A; Verma, S; Loibl, S; Crawford, J; Choi, MR; Dreiling, L; Vandenberg, T
MLA Citation
Chan, A, Verma, S, Loibl, S, Crawford, J, Choi, MR, Dreiling, L, and Vandenberg, T. "Reporting of myelotoxicity associated with emerging regimens for the treatment of selected solid tumors." Critical Reviews in Oncology/Hematology 81.2 (2012): 136-150.
PMID
21507676
Source
scival
Published In
Critical Reviews in Oncology/Hematology
Volume
81
Issue
2
Publish Date
2012
Start Page
136
End Page
150
DOI
10.1016/j.critrevonc.2011.03.003

Small-cell lung cancer: Prognostic factors and changing treatment over 15 years

Background: The incidence of small-cell lung cancer (SCLC) has decreased over several decades. Sixty-eight thousand six hundred eleven patients with SCLC in the National Cancer Data Base (NCDB) were analyzed to describe demographic, treatment, and survival changes between 1992 and 2007. Methods and Materials: Four patient cohortsdiagnosed in 1992, 1997, 2002, and 2007were examined. Univariate and multivariate analyses were performed to determine changes in demographic and treatment factors and their effect on survival of limited SCLC (LSCLC) and extensive SCLC (ESCLC). Results: The proportion of female patients increased, whereas the proportion of non-Hispanic white patients decreased. Median survival for patients with ESCLC and LSCLC was 6.1 and 12.9 months, respectively, and was not significantly improved between patients diagnosed in 1992 and 2002. Improved survival was associated with female sex, age < 70 years, and receipt of surgery for patients with LSCLC. Radiation therapy decreased the hazard ratio (HR) for patients with stage III LSCLC but not for patients with earlier stage disease. Chemotherapy decreased the HR for all patients with LSCLC. Patients with ESCLC treated with radiation in addition to chemotherapy had better survival than those who received only chemotherapy. Conclusions: Despite changes in demographics and treatment, the median and 5-year survival rates for patients with SCLC have not significantly improved over the past 15 years. Surgery was associated with improved survival in LSCLC. The benefit of chemotherapy and/or radiation therapy was dependent on American Joint Committee on Cancer (AJCC) stage. AJCC staging information had prognostic and treatment ramifications and should be collected in future studies and databases. © 2012 Elsevier Inc. All rights reserved.

Authors
Gaspar, LE; McNamara, EJ; Gay, EG; Putnam, JB; Crawford, J; Herbst, RS; Bonner, JA
MLA Citation
Gaspar, LE, McNamara, EJ, Gay, EG, Putnam, JB, Crawford, J, Herbst, RS, and Bonner, JA. "Small-cell lung cancer: Prognostic factors and changing treatment over 15 years." Clinical Lung Cancer 13.2 (2012): 115-122.
PMID
22000695
Source
scival
Published In
Clinical lung cancer
Volume
13
Issue
2
Publish Date
2012
Start Page
115
End Page
122
DOI
10.1016/j.cllc.2011.05.008

Changing Patterns of Chemotherapy Delivery and Supportive Care for Aggressive B-Cell Non-Hodgkin's Lymphoma

Authors
Lyman, GH; Crawford, J; Dale, DC; Whittaker, S; Tomita, D
MLA Citation
Lyman, GH, Crawford, J, Dale, DC, Whittaker, S, and Tomita, D. "Changing Patterns of Chemotherapy Delivery and Supportive Care for Aggressive B-Cell Non-Hodgkin's Lymphoma." November 18, 2011.
PMID
25926064
Source
wos-lite
Published In
Blood
Volume
118
Issue
21
Publish Date
2011
Start Page
1147
End Page
1147

Pulmonary toxicity in Stage III non-small cell lung cancer patients treated with high-dose (74 Gy) 3-dimensional conformal thoracic radiotherapy and concurrent chemotherapy following induction chemotherapy: a secondary analysis of Cancer and Leukemia Group B (CALGB) trial 30105.

PURPOSE: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. METHODS AND MATERIALS: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. RESULTS: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. CONCLUSIONS: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

Authors
Salama, JK; Stinchcombe, TE; Gu, L; Wang, X; Morano, K; Bogart, JA; Crawford, JC; Socinski, MA; Blackstock, AW; Vokes, EE; Cancer and Leukemia Group B,
MLA Citation
Salama, JK, Stinchcombe, TE, Gu, L, Wang, X, Morano, K, Bogart, JA, Crawford, JC, Socinski, MA, Blackstock, AW, Vokes, EE, and Cancer and Leukemia Group B, . "Pulmonary toxicity in Stage III non-small cell lung cancer patients treated with high-dose (74 Gy) 3-dimensional conformal thoracic radiotherapy and concurrent chemotherapy following induction chemotherapy: a secondary analysis of Cancer and Leukemia Group B (CALGB) trial 30105." Int J Radiat Oncol Biol Phys 81.4 (November 15, 2011): e269-e274.
PMID
21477940
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
81
Issue
4
Publish Date
2011
Start Page
e269
End Page
e274
DOI
10.1016/j.ijrobp.2011.01.056

Comparison of demographic characteristics, surgical resection patterns, and survival outcomes for veterans and nonveterans with non-small cell lung cancer in the Pacific Northwest.

INTRODUCTION: Lung cancer is a leading cause of death in the United States and among veterans. This study compares patterns of diagnosis, treatment, and survival for veterans diagnosed with non-small cell lung cancer (NSCLC) using a recently established cancer registry for the Veterans Affairs Pacific Northwest Network with the Puget Sound Surveillance, Epidemiology, and End Results cancer registry. METHODS: A cohort of 1715 veterans with NSCLC were diagnosed between 2000 and 2006, and 7864 men were diagnosed in Washington State during the same period. Demographics, tumor characteristics, initial surgical patterns, and survival across the two registries were evaluated. RESULTS: Veterans were more likely to be diagnosed with stage I or II disease (32.8%) compared with the surrounding community (21.5%, p = 0.001). Surgical resection rates were similar for veterans (70.2%) and nonveterans (71.2%) older than 65 years with early-stage disease (p = 0.298). However, veterans younger than 65 years with early-stage disease were less likely to undergo surgical resection (83.3% versus 91.5%, p = 0.003). Because there were fewer late-stage patients among veterans, overall survival was better, although within each stage group veterans experienced worse survival compared with community patients. The largest differences were among early-stage patients with 44.6% 5-year survival for veterans compared with 57.4% for nonveterans (p = 0.004). CONCLUSIONS: The use of surgical resection among younger veterans with NSCLC may be lower compared with the surrounding community and may be contributing to poorer survival. Cancer quality of care studies have primarily focused on patients older than 65 years using Medicare claims; however, efforts to examine care for younger patients within and outside the Department of Veterans Affairs are needed.

Authors
Zeliadt, SB; Sekaran, NK; Hu, EY; Slatore, CC; Au, DH; Backhus, L; Wu, DY; Crawford, J; Lyman, GH; Dale, DC
MLA Citation
Zeliadt, SB, Sekaran, NK, Hu, EY, Slatore, CC, Au, DH, Backhus, L, Wu, DY, Crawford, J, Lyman, GH, and Dale, DC. "Comparison of demographic characteristics, surgical resection patterns, and survival outcomes for veterans and nonveterans with non-small cell lung cancer in the Pacific Northwest." J Thorac Oncol 6.10 (October 2011): 1726-1732.
PMID
21857253
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
6
Issue
10
Publish Date
2011
Start Page
1726
End Page
1732
DOI
10.1097/JTO.0b013e31822ada77

Myeloid growth factors.

Authors
Crawford, J; Allen, J; Armitage, J; Blayney, DW; Cataland, SR; Heaney, ML; Htoy, S; Hudock, S; Kloth, DD; Kuter, DJ; Lyman, GH; McMahon, B; Steensma, DP; Vadhan-Raj, S; Westervelt, P; Westmoreland, M; National Comprehensive Cancer Network,
MLA Citation
Crawford, J, Allen, J, Armitage, J, Blayney, DW, Cataland, SR, Heaney, ML, Htoy, S, Hudock, S, Kloth, DD, Kuter, DJ, Lyman, GH, McMahon, B, Steensma, DP, Vadhan-Raj, S, Westervelt, P, Westmoreland, M, and National Comprehensive Cancer Network, . "Myeloid growth factors." J Natl Compr Canc Netw 9.8 (August 1, 2011): 914-932.
PMID
21900221
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
8
Publish Date
2011
Start Page
914
End Page
932

Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy.

BACKGROUND: A prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications in cancer patients receiving chemotherapy. METHODS: The study population consisted of 3760 patients with common solid tumors or malignant lymphoma who were beginning a new chemotherapy regimen at 115 practice sites throughout the United States. A regression model for neutropenic complications was developed and then validated by using a random split-sample selection process. RESULTS: No significant differences in the derivation and validation populations were observed. The risk of neutropenic complications was greatest in cycle 1 with no significant difference in predicted risk between the 2 cohorts in univariate analysis. After adjustment for cancer type and age, major independent risk factors in multivariate analysis included: prior chemotherapy, abnormal hepatic and renal function, low white blood count, chemotherapy and planned delivery ≥85%. At a predicted risk cutpoint of 10%, model test performance included: sensitivity 90%, specificity 59%, and predictive value positive and negative of 34% and 96%, respectively. Further analysis confirmed model discrimination for risk of febrile neutropenia over multiple chemotherapy cycles. CONCLUSIONS: A risk model for neutropenic complications was developed and validated in a large prospective cohort of patients who were beginning cancer chemotherapy that may guide the effective and cost-effective use of available supportive care.

Authors
Lyman, GH; Kuderer, NM; Crawford, J; Wolff, DA; Culakova, E; Poniewierski, MS; Dale, DC
MLA Citation
Lyman, GH, Kuderer, NM, Crawford, J, Wolff, DA, Culakova, E, Poniewierski, MS, and Dale, DC. "Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy." Cancer 117.9 (May 1, 2011): 1917-1927.
PMID
21509769
Source
pubmed
Published In
Cancer
Volume
117
Issue
9
Publish Date
2011
Start Page
1917
End Page
1927
DOI
10.1002/cncr.25691

Phase II multicenter trial of voreloxin as second-line therapy in chemotherapy-sensitive or refractory small cell lung cancer

Voreloxin is an anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, causing double-strand breaks in DNA, irreversible G2 arrest, and rapid onset of apoptosis. Based on preclinical activity of voreloxin in chemoresistant tumors, early phase I clinical activity, and a mechanism of action similar to other topoisomerase II inhibitors such as the anthracyclines and etoposide, this phase II trial was undertaken as second-line treatment of small cell lung cancer (SCLC). Methods: Patients with extensive stage SCLC previously treated with one prior chemotherapy regimen were eligible. Patients with chemotherapy-sensitive or chemotherapy-refractory disease were considered as separate cohorts. Voreloxin (48 mg/m2) was administered on the first day of each 21-day cycle for up to six cycles. The primary end point was objective response rate. Results: Fifty-five patients were enrolled including 28 with refractory SCLC and 27 with sensitive SCLC; 47 were evaluable for response. Three patients with sensitive SCLC had an objective response, including one complete response and two partial responses (11% response rate based on intent to treat). No patients in the refractory cohort had a response. The primary grade 3 toxicity was neutropenia. Conclusion: Voreloxin has minimal activity in relapsed SCLC when administered at 48 mg/m in a 3-week schedule. Copyright © 2011 by the International Association for the Study of Lung Cancer.

Authors
Krug, LM; Crawford, J; Ettinger, DS; Shapiro, GI; Spigel, D; Reiman, T; Temel, JS; Michelson, GC; Young, DY; Hoch, U; Adelman, DC
MLA Citation
Krug, LM, Crawford, J, Ettinger, DS, Shapiro, GI, Spigel, D, Reiman, T, Temel, JS, Michelson, GC, Young, DY, Hoch, U, and Adelman, DC. "Phase II multicenter trial of voreloxin as second-line therapy in chemotherapy-sensitive or refractory small cell lung cancer." Journal of Thoracic Oncology 6.2 (2011): 384-386.
PMID
21252718
Source
scival
Published In
Journal of Thoracic Oncology
Volume
6
Issue
2
Publish Date
2011
Start Page
384
End Page
386
DOI
10.1097/JTO.0b013e318200e509

A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307.

HYPOTHESIS: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. METHODS: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. RESULTS: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). CONCLUSION: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted.

Authors
Dubey, S; Jänne, PA; Krug, L; Pang, H; Wang, X; Heinze, R; Watt, C; Crawford, J; Kratzke, R; Vokes, E; Kindler, HL
MLA Citation
Dubey, S, Jänne, PA, Krug, L, Pang, H, Wang, X, Heinze, R, Watt, C, Crawford, J, Kratzke, R, Vokes, E, and Kindler, HL. "A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307." J Thorac Oncol 5.10 (October 2010): 1655-1661.
PMID
20736856
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
5
Issue
10
Publish Date
2010
Start Page
1655
End Page
1661
DOI
10.1097/JTO.0b013e3181ec18db

Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review.

PURPOSE: To evaluate the risk of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and overall mortality in patients receiving chemotherapy with or without granulocyte colony-stimulating factor (G-CSF), a systematic review of randomized controlled trials (RCTs) was conducted. METHODS: Electronic databases searched through October 2008 identified 3,794 articles for initial screening. Eligibility included solid tumor or lymphoma patients randomly assigned to chemotherapy with or without G-CSF support, > or = 2 years of follow-up, and reporting AML/MDS or all second malignancies. Dual blinded data extraction was performed. Relative risk (RR) and absolute risk (AR) estimates +/- 95% CIs were calculated by the Mantel-Haenszel method. RESULTS: In the 25 eligible RCTs, 6,058 and 6,746 patients were randomly assigned to receive chemotherapy with and without initial G-CSF support, respectively. At mean and median follow-up across studies of 60 and 53 months, respectively, AML/MDS was reported in 22 control patients and 43 G-CSF-treated patients, with an estimated RR of 1.92 (95% CI, 1.19 to 3.07; P = .007) and AR increase of 0.41% (95% CI, 0.10% to 0.72%; P = .009). Deaths were reported in 1,845 patients randomly assigned to G-CSF and in 2,099 controls, for estimates of RR and AR decrease of 0.897 (95% CI, 0.857 to 0.938; P < .001) and 3.40% (95% CI, 2.01% to 4.80%; P < .001), respectively. Greater RR reduction for mortality was seen for both larger studies (P = .05) and greater chemotherapy dose-intensity (P = .012). CONCLUSION: Delivered chemotherapy dose-intensity and risk of AML/MDS are increased but all-cause mortality is decreased in patients receiving chemotherapy with G-CSF support. Greater reductions in mortality were observed with greater chemotherapy dose-intensity.

Authors
Lyman, GH; Dale, DC; Wolff, DA; Culakova, E; Poniewierski, MS; Kuderer, NM; Crawford, J
MLA Citation
Lyman, GH, Dale, DC, Wolff, DA, Culakova, E, Poniewierski, MS, Kuderer, NM, and Crawford, J. "Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review." J Clin Oncol 28.17 (June 10, 2010): 2914-2924. (Review)
PMID
20385991
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
17
Publish Date
2010
Start Page
2914
End Page
2924
DOI
10.1200/JCO.2009.25.8723

Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications.

Authors
Crawford, J; Caserta, C; Roila, F; ESMO Guidelines Working Group,
MLA Citation
Crawford, J, Caserta, C, Roila, F, and ESMO Guidelines Working Group, . "Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications." Ann Oncol 21 Suppl 5 (May 2010): v248-v251.
PMID
20555091
Source
pubmed
Published In
Annals of Oncology
Volume
21 Suppl 5
Publish Date
2010
Start Page
v248
End Page
v251
DOI
10.1093/annonc/mdq195

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design.

BACKGROUND: The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak), patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC) patients. METHODS/DESIGN: Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression. DISCUSSION: VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum. TRIAL REGISTRATION: NCT00018255.

Authors
Jones, LW; Eves, ND; Kraus, WE; Potti, A; Crawford, J; Blumenthal, JA; Peterson, BL; Douglas, PS
MLA Citation
Jones, LW, Eves, ND, Kraus, WE, Potti, A, Crawford, J, Blumenthal, JA, Peterson, BL, and Douglas, PS. "The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design. (Published online)" BMC Cancer 10 (April 21, 2010): 155-.
Website
http://hdl.handle.net/10161/4354
PMID
20409311
Source
pubmed
Published In
BMC Cancer
Volume
10
Publish Date
2010
Start Page
155
DOI
10.1186/1471-2407-10-155

Age- and sex-specific genomic profiles in non-small cell lung cancer.

CONTEXT: Gene expression profiling may be useful in examining differences underlying age- and sex-specific outcomes in non-small cell lung cancer (NSCLC). OBJECTIVE: To describe clinically relevant differences in the underlying biology of NSCLC based on patient age and sex. DESIGN, SETTING, AND PATIENTS: Retrospective analysis of 787 patients with predominantly early stage NSCLC performed at Duke University, Durham, North Carolina, from July 2008 to June 2009. Lung tumor samples with corresponding microarray and clinical data were used. All patients were divided into subgroups based on age (< 70 vs > or = 70 years old) or sex. Gene expression signatures representing oncogenic pathway activation and tumor biology/microenvironment status were applied to these samples to obtain patterns of activation/deregulation. MAIN OUTCOME MEASURES: Patterns of oncogenic and molecular signaling pathway activation that are reproducible and correlate with 5-year recurrence-free patient survival. RESULTS: Low- and high-risk patient clusters/cohorts were identified with the longest and shortest 5-year recurrence-free survival, respectively, within the age and sex NSCLC subgroups. These cohorts of NSCLC demonstrate similar patterns of pathway activation. In patients younger than 70 years, high-risk patients, with the shortest recurrence-free survival, demonstrated increased activation of the Src (25% vs 6%; P<.001) and tumor necrosis factor (76% vs 42%; P<.001) pathways compared with low-risk patients. High-risk patients aged 70 years or older demonstrated increased activation of the wound healing (40% vs 24%; P = .02) and invasiveness (64% vs 20%; P<.001) pathways compared with low-risk patients. In women, high-risk patients demonstrated increased activation of the invasiveness (99% vs 2%; P<.001) and STAT3 (72% vs 35%; P<.001) pathways while high-risk men demonstrated increased activation of the STAT3 (87% vs 18%; P<.001), tumor necrosis factor (90% vs 46%; P<.001), EGFR (13% vs 2%; P = .003), and wound healing (50% vs 22%; P<.001) pathways. Multivariate analyses confirmed the independent clinical relevance of the pathway-based subphenotypes in women (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.34-3.03; P<.001) and patients younger than 70 years (HR, 1.83; 95% CI, 1.24-2.71; P = .003). All observations were reproducible in split sample analyses. CONCLUSIONS: Among a cohort of patients with NSCLC, subgroups defined by oncogenic pathway activation profiles were associated with recurrence-free survival. These findings require validation in independent patient data sets.

Authors
Mostertz, W; Stevenson, M; Acharya, C; Chan, I; Walters, K; Lamlertthon, W; Barry, W; Crawford, J; Nevins, J; Potti, A
MLA Citation
Mostertz, W, Stevenson, M, Acharya, C, Chan, I, Walters, K, Lamlertthon, W, Barry, W, Crawford, J, Nevins, J, and Potti, A. "Age- and sex-specific genomic profiles in non-small cell lung cancer." JAMA 303.6 (February 10, 2010): 535-543.
PMID
20145230
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
303
Issue
6
Publish Date
2010
Start Page
535
End Page
543
DOI
10.1001/jama.2010.80

Preoperative radiation therapy and chemotherapy for pulmonary blastoma: a case report.

Authors
Zagar, TM; Blackwell, S; Crawford, J; D'Amico, T; Christensen, JD; Sporn, TA; Kelsey, CR
MLA Citation
Zagar, TM, Blackwell, S, Crawford, J, D'Amico, T, Christensen, JD, Sporn, TA, and Kelsey, CR. "Preoperative radiation therapy and chemotherapy for pulmonary blastoma: a case report." J Thorac Oncol 5.2 (February 2010): 282-283.
PMID
20101153
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
5
Issue
2
Publish Date
2010
Start Page
282
End Page
283
DOI
10.1097/JTO.0b013e3181c420e1

Erythropoiesis-stimulating agents in older adults with cancer

© Cambridge University Press 2010.Introduction The prevalence of anemia in older persons is higher than in the general population and is associated with significant clinical symptoms and poorer prognosis in this group. An increased incidence of cancer and the use of cytotoxic agents in this population also places patients at increased risk of development of anemia and consequently may also increase their morbidity/mortality risk. Since the introduction of erythropoiesis-stimulating agents (ESAs), clinicians have sought potential uses of these agents to treat cancer-related anemia. Though studies demonstrated an improvement in anemia, reduction in blood transfusion, and improved quality of life, there was hope that mortality would also be improved. However, some recent reports have shown possible adverse effects of ESAs on tumor progression and survival in patients being treated for cancer. In this chapter, we review the effects of anemia on the prognosis of geriatric cancer patients, consider the rationale for use of ESAs versus other therapies for cancer-related anemia, and discuss some of the recent reports regarding potential adverse effects of ESAs, resulting in current guidelines of usage of ESAs. Prevalence and morbidity/mortality associated with anemia in the aged Anemia is significantly more prevalent in the aged population, and there are ample data to suggest that this is associated with poor outcomes. The prevalence of anemia by World Health Organization criteria (hgb less than 13 gm/dL in men and hgb less than 12 gm/dL in women) in the geriatric population has been reported to be approximately 11–28 percent in persons over 65 years of age.

Authors
McKinney, MS; Crawford, J
MLA Citation
McKinney, MS, and Crawford, J. "Erythropoiesis-stimulating agents in older adults with cancer." Practical Geriatric Oncology. January 1, 2010. 338-350.
Source
scopus
Publish Date
2010
Start Page
338
End Page
350
DOI
10.1017/CBO9780511763182.024

Reply to N. Lathia et al

Authors
Kuderer, NM; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Kuderer, NM, Dale, DC, Crawford, J, and Lyman, GH. "Reply to N. Lathia et al." Journal of Clinical Oncology 28.36 (2010): e764-.
Source
scival
Published In
Journal of Clinical Oncology
Volume
28
Issue
36
Publish Date
2010
Start Page
e764
DOI
10.1200/JCO.2010.30.5607

Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: Where are we now?

Updated international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor (G-CSF) in supporting delivery of myelosuppressive chemotherapy. G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia (FN) due to regimen and individual patient factors is <20%, for supporting dose-dense and doseintense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes. Indeed, there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy. Predictive tools that can help target those patients who are most at risk of FN are now becoming available. Recent analyses have shown that, by reducing the risk of FN and chemotherapy dose delays and reductions, G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative settings. Accumulating data from 'real-world' clinical practice settings indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection. A single dose of PEGylated G-CSF (pegfilgrastim) may provide a more effective, as well as a more convenient, alternative to daily G-CSF. Prospective studies are needed to validate the importance of delivering the full dose intensity of standard chemotherapy regimens, with G-CSF support where appropriate, across a range of settings. These studies should also incorporate prospective evaluation of risk stratification for neutropenia and its complications. © The Author(s) 2010.

Authors
Aapro, M; Crawford, J; Kamioner, D
MLA Citation
Aapro, M, Crawford, J, and Kamioner, D. "Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: Where are we now?." Supportive Care in Cancer 18.5 (2010): 529-541.
PMID
20191292
Source
scival
Published In
Supportive Care in Cancer
Volume
18
Issue
5
Publish Date
2010
Start Page
529
End Page
541
DOI
10.1007/s00520-010-0816-y

Erythropoiesis-stimulating agents in oncology: A study-level meta-analysis of survival and other safety outcomes

Background: Cancer patients often develop the potentially debilitating condition of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in anaemic cancer patients receiving chemotherapy. To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events. Methods: This meta-analysis included studies from the 2006 Cochrane meta-analysis, studies published/updated since the 2006 Cochrane report, and unpublished trial data from Amgen and Centocor Ortho Biotech. The 60 studies analysed (15 323 patients) were conducted in the settings of chemotherapy/radiochemotherapy, radiotherapy only treatment or anaemia of cancer. Data were summarised using odds ratios (ORs) with 95% confidence intervals (CIs). Results: Results indicated that ESA use did not significantly affect mortality (60 studies: OR1.06; 95% CI: 0.97-1.15) or disease progression (26 studies: OR1.01; 95% CI: 0.90-1.14), but increased the risk for venous-thromoboembolic events (44 studies: OR1.48; 95% CI: 1.28-1.72). Conclusion: Though this meta-analysis showed no significant effect of ESAs on survival or disease progression, prospectively designed, future randomised clinical trials will further examine the safety and efficacy of ESAs when used according to the revised labelling information. © 2010 Cancer Research UK. All rights reserved.

Authors
Glaspy, J; Crawford, J; Vansteenkiste, J; Henry, D; Rao, S; Bowers, P; Berlin, JA; Tomita, D; Bridges, K; Ludwig, H
MLA Citation
Glaspy, J, Crawford, J, Vansteenkiste, J, Henry, D, Rao, S, Bowers, P, Berlin, JA, Tomita, D, Bridges, K, and Ludwig, H. "Erythropoiesis-stimulating agents in oncology: A study-level meta-analysis of survival and other safety outcomes." British Journal of Cancer 102.2 (2010): 301-315.
PMID
20051958
Source
scival
Published In
British Journal of Cancer
Volume
102
Issue
2
Publish Date
2010
Start Page
301
End Page
315
DOI
10.1038/sj.bjc.6605498

Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma.

PURPOSE: Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities are the result of a common biological phenotype, such as regulatory pathways. EXPERIMENTAL DESIGN: Lung cancer cell lines with corresponding gene expression data and genes associated with an embryonic stem cell identity were used to develop a signature of embryonic stemness (ES) activity specific to lung adenocarcinoma. Biological characteristics were elucidated as a function of cancer biology/oncogenic pathway dysregulation. The ES signature was applied to three independent early-stage (I-IIIa) lung adenocarcinoma data sets with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin (current standard of care) sensitivity was evaluated. RESULTS: Pathway analysis identified specific regulatory networks [Ras (P = 0.0005), Myc (P = 0.0224), wound healing (P < 0.0001), chromosomal instability (P < 0.0001), and invasiveness (P < 0.0001)] associated with the ES phenotype. The prognostic relevance of the ES signature, as related to patient survival, was characterized in three cohorts [CALGB 9761 (n = 82; P = 0.0001), National Cancer Institute Director's Challenge Consortium (n = 442; P = 0.0002), and Duke (n = 45; P = 0.06)]. The ES signature was not prognostic in prostate, breast, or ovarian adenocarcinomas. Lung tumors (n = 569) and adenocarcinoma cell lines (n = 31) expressing the ES phenotype were more likely to be resistant to cisplatin (P < 0.0001 and P = 0.006, respectively). CONCLUSIONS: Lung adenocarcinomas that share a common gene expression pattern with normal human embryonic stem cells were associated with decreased survival, increased biological complexity, and increased likelihood of resistance to cisplatin. This indicates the aggressiveness of these tumors.

Authors
Stevenson, M; Mostertz, W; Acharya, C; Kim, W; Walters, K; Barry, W; Higgins, K; Tuchman, SA; Crawford, J; Vlahovic, G; Ready, N; Onaitis, M; Potti, A
MLA Citation
Stevenson, M, Mostertz, W, Acharya, C, Kim, W, Walters, K, Barry, W, Higgins, K, Tuchman, SA, Crawford, J, Vlahovic, G, Ready, N, Onaitis, M, and Potti, A. "Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma." Clin Cancer Res 15.24 (December 15, 2009): 7553-7561.
PMID
19996213
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
24
Publish Date
2009
Start Page
7553
End Page
7561
DOI
10.1158/1078-0432.CCR-09-1939

Dose intensity and hematologic toxicity in older breast cancer patients receiving systemic chemotherapy.

BACKGROUND: This prospective study evaluated patient and treatment characteristics that contributed to hematologic toxicity in older breast cancer patients treated with curative intent in the community setting. METHODS: Data were collected on 1224 patients with stage I through III breast cancer, of whom 207 were aged > or =65 years (grading determined according to the American Joint Committee on Cancer staging system). Primary outcome measures included anemia, thrombocytopenia, severe neutropenia, febrile neutropenia, and both planned and actual relative dose intensity (RDI). Comparisons between older and younger patients regarding hematologic toxicity and reductions in RDI were based on univariate and multivariate logistic regression analyses. RESULTS: The neutropenic complication rate in older patients (45.1%) was not significantly different from that in the younger patients (43.7%). There were also no significant differences in rates of anemia or thrombocytopenia. Approximately 34.0% of the older patients received RDI <85% compared with 20.0% among younger patients (P < .01). Fewer older patients received anthracycline-based chemotherapy (64.3% compared with 83.8% in younger patients, P < .01). Fewer older patients received prophylactic white blood cell colony-stimulating factor (18.4%) compared with younger patients (28.0%) (P < .01). CONCLUSIONS: There were no significant differences noted with regard to chemotherapy-related hematologic toxicities between older and younger breast cancer patients in this large prospective observational study. This may be explained, in part, by more frequent reductions in RDI and less frequent utilization of anthracyclines among older patients.

Authors
Shayne, M; Culakova, E; Wolff, D; Poniewierski, MS; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Shayne, M, Culakova, E, Wolff, D, Poniewierski, MS, Dale, DC, Crawford, J, and Lyman, GH. "Dose intensity and hematologic toxicity in older breast cancer patients receiving systemic chemotherapy." Cancer 115.22 (November 15, 2009): 5319-5328.
PMID
19672945
Source
pubmed
Published In
Cancer
Volume
115
Issue
22
Publish Date
2009
Start Page
5319
End Page
5328
DOI
10.1002/cncr.24560

Hematopoietic growth factors: ESMO recommendations for the applications.

Authors
Crawford, J; Caserta, C; Roila, F; ESMO Guidelines Working Group,
MLA Citation
Crawford, J, Caserta, C, Roila, F, and ESMO Guidelines Working Group, . "Hematopoietic growth factors: ESMO recommendations for the applications." Ann Oncol 20 Suppl 4 (May 2009): 162-165. (Review)
PMID
19454444
Source
pubmed
Published In
Annals of Oncology
Volume
20 Suppl 4
Publish Date
2009
Start Page
162
End Page
165
DOI
10.1093/annonc/mdp162

Myeloid growth factors.

Authors
Crawford, J; Armitage, J; Balducci, L; Bennett, C; Blayney, DW; Cataland, SR; Dale, DC; Demetri, GD; Erba, HP; Foran, J; Freifeld, AG; Goemann, M; Heaney, ML; Htoy, S; Hudock, S; Kloth, DD; Kuter, DJ; Lyman, GH; Michaud, LB; Miyata, SC; Tallman, MS; Vadhan-Raj, S; Westervelt, P; Wong, MK; National Comprehensive Cancer Network,
MLA Citation
Crawford, J, Armitage, J, Balducci, L, Bennett, C, Blayney, DW, Cataland, SR, Dale, DC, Demetri, GD, Erba, HP, Foran, J, Freifeld, AG, Goemann, M, Heaney, ML, Htoy, S, Hudock, S, Kloth, DD, Kuter, DJ, Lyman, GH, Michaud, LB, Miyata, SC, Tallman, MS, Vadhan-Raj, S, Westervelt, P, Wong, MK, and National Comprehensive Cancer Network, . "Myeloid growth factors." J Natl Compr Canc Netw 7.1 (January 2009): 64-83.
PMID
19176207
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
7
Issue
1
Publish Date
2009
Start Page
64
End Page
83

Pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials of darbepoetin alfa in the treatment of patients with chemotherapy-induced anemia

Purpose: Although numerous clinical trials have demonstrated the efficacy and tolerability of erythropoiesis-stimulating agents (ESAs) in patients with chemotherapy-induced anemia (CIA), results of some recent trials and one meta-analysis have suggested that ESAs may negatively impact survival and/or disease control in patients with cancer. Methods: To assess the benefits and risks of ESAs in CIA, we conducted a pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials in 2,122 patients with CIA receiving darbepoetin alfa (DA; n = 1,200) or placebo (n = 912). Results: DA did not increase mortality (hazard ratio = 0.97; 95% CI, 0.85 to 1.1) and had no effect on progression-free survival (hazard ratio = 0.93; 95% CI, 0.84 to 1.04) and disease progression (hazard ratio = 0.92; 95% CI, 0.82 to 1.03), but, as expected, increased the risk for thromboembolic events (hazard ratio = 1.57; 95% CI, 1.10 to 2.26). Overall and progression-free survival were not affected by baseline hemoglobin and seemed better in patients who achieved hemoglobin more than 12 or more than 13 g/dL. Transfusions and rates of hemoglobin increase (> 1 g/dL in 14 days; > 2 g/dL in 28 days) owing to transfusions were associated with an increased risk for death and disease progression in both treatment groups; in the absence of transfusions, rates of hemoglobin increase did not appear to increase the risk for adverse outcomes. Compared with placebo, DA significantly reduced the risk of receiving one or more transfusion. Conclusion: There seemed to be no association between DA and risk of death or disease progression in this meta-analysis of individual patient data from DA studies conducted in CIA, the approved indication for ESAs in oncology. Copyright © 2009 by the American Society of Clinical Oncology.

Authors
Ludwig, H; Crawford, J; Österborg, A; Vansteenkiste, J; Henry, DH; Fleishman, A; Bridges, K; Glaspy, JA
MLA Citation
Ludwig, H, Crawford, J, Österborg, A, Vansteenkiste, J, Henry, DH, Fleishman, A, Bridges, K, and Glaspy, JA. "Pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials of darbepoetin alfa in the treatment of patients with chemotherapy-induced anemia." Journal of Clinical Oncology 27.17 (2009): 2838-2847.
PMID
19380447
Source
scival
Published In
Journal of Clinical Oncology
Volume
27
Issue
17
Publish Date
2009
Start Page
2838
End Page
2847
DOI
10.1200/JCO.2008.19.1130

A phase II trial of denileukin diftitox in patients with previously treated advanced non-small cell lung cancer

Introduction: Denileukin diftitox, a chimeric protein, uses the cytocidal properties of diphtheria toxin to cells expressing interleukin-2 receptors. The aim of this study was to evaluate the efficacy and safety of denileukin diftitox in the treatment of advanced relapsed nonsmall cell lung cancer (NSCLC). Patients And Methods: Multicenter phase II trial in patients with NSCLC with Eastern Cooperative Oncology Group PS 0-2, stage IIIB/IV at diagnosis, who had failed at least 1 previous chemotherapy regimen. Denileukin diftitox was infused at 18 μg/kg/d × 5 days, every 21 days for 6 cycles. Results: For the 41 patients enrolled, the median age was 56 years (range, 21-80), 25 were men, and the median number of previous chemotherapy regimens was 2 (range, 1-5). The median number of treatment cycles was 2 (range, 1-6). By RECIST criteria, 18 (44%) had stable disease, 10 (24%) progressive disease, and 13 (32%) were not evaluable for response as they received less than 2 treatment cycles. The median time to disease progression was 1.8 months [range, 0.3-11.3; 95% confidence interval (CI) 1.3-2.6]. Median survival was 5.8 months (range, 0.3-33.6; 95% CI 3.4-11.4). The median follow-up time was 16.1 month. One death from myocarditis verified at autopsy was attributed to treatment. One grade 4 toxicity (vascular leak syndrome) was encountered, and 18 grade 3 toxicities, primarily gastrointestinal, vascular leak syndrome, and constitutional symptoms. Conclusion: Denileukin diftitox at current dose schedule has limited activity in patients with previously treated NSCLC, manifested by disease control without impact on survival. Copyright © 2009 by Lippincott Williams & Wilkins.

Authors
Gerena-Lewis, M; Crawford, J; Bonomi, P; Maddox, AM; Hainsworth, J; McCune, DE; Shukla, R; Zeigler, H; Hurtubise, P; Chowdhury, TR; Fletcher, B; Dyehouse, K; Ghalie, R; Jazieh, AR
MLA Citation
Gerena-Lewis, M, Crawford, J, Bonomi, P, Maddox, AM, Hainsworth, J, McCune, DE, Shukla, R, Zeigler, H, Hurtubise, P, Chowdhury, TR, Fletcher, B, Dyehouse, K, Ghalie, R, and Jazieh, AR. "A phase II trial of denileukin diftitox in patients with previously treated advanced non-small cell lung cancer." American Journal of Clinical Oncology: Cancer Clinical Trials 32.3 (2009): 269-273.
PMID
19433964
Source
scival
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
32
Issue
3
Publish Date
2009
Start Page
269
End Page
273
DOI
10.1097/COC.0b013e318187dd40

Cancer diagnostic assessment programs: Standards for the organization of care in Ontario

Background: Improving access to better, more efficient, and rapid cancer diagnosis is a necessary component of a high-quality cancer system. How diagnostic services ought to be organized, structured, and evaluated is less understood and studied. Our objective was to address this gap. Methods: As a quality initiative of Cancer Care Ontario's Program in Evidence-Based Care, the Diagnostic Assessment Standards Panel, with representation from clinical oncology experts, institutional and clinical administrative leaders, health service researchers, and methodologists, conducted a systematic review and a targeted environmental scan of the unpublished literature. Standards were developed based on expert consensus opinion informed by the identified evidence. Through external review, clinicians and administrators across Ontario were given the opportunity to provide feedback. Results: The body of evidence consists of thirty-five published studies and fifteen unpublished guidance documents. The evidence and consensus opinion consistently favoured an organized, centralized system with multidisciplinary team membership as the optimal approach for the delivery of diagnostic cancer assessment services. Independent external stakeholders agreed (with higher mean values, maximum 5, indicating stronger agreement) that dap standards are needed (mean: 4.6), that standards should be formally approved (mean: 4.3), and importantly, that standards reflect an effective approach that will lead to quality improvements in the cancer system (mean: 4.5) and in patient care (mean: 4.3). Interpretation: Based on the best available evidence, standards for the organization of daps are offered. There is clear need to integrate formal and comprehensive evaluation strategies with the implementation of the standards to advance this field. Copyright © 2009 Multimed Inc.

Authors
Brouwers, M; Oliver, TK; Crawford, J; Ellison, P; Evans, WK; Gagliardi, A; Lacourciere, J; Lo, D; Mai, V; McNair, S; Minuk, T; Rabeneck, L; Rand, C; Ross, J; Smylie, J; Srigley, J; Stern, H; Trudeau, M
MLA Citation
Brouwers, M, Oliver, TK, Crawford, J, Ellison, P, Evans, WK, Gagliardi, A, Lacourciere, J, Lo, D, Mai, V, McNair, S, Minuk, T, Rabeneck, L, Rand, C, Ross, J, Smylie, J, Srigley, J, Stern, H, and Trudeau, M. "Cancer diagnostic assessment programs: Standards for the organization of care in Ontario." Current Oncology 16.6 (2009): 29-41.
Source
scival
Published In
Current oncology (Toronto, Ont.)
Volume
16
Issue
6
Publish Date
2009
Start Page
29
End Page
41

An open-label clinical trial evaluating safety and pharmacokinetics of two dosing schedules of panitumumab in patients with solid tumors

Purpose: This study evaluated safety, pharmacokinetics, and efficacy of 2 dose schedules and 2 infusion times of panitumumab in patients with advanced solid malignancies. Patients and Methods: This phase I multicenter, open-label study sequentially enrolled patients with advanced solid tumors refractory to standard therapy, or for which no standard therapy exists, to receive panitumumab 6 mg/kg every 2 weeks or 9 mg/kg every 3 weeks. Patients receiving panitumumab every 2 weeks received either all infusions over 60 minutes or a 60-minute infusion for the first dose followed by 30-minute infusions if the first infusion was well tolerated. Patients in the every-3-week cohort received 60-minute infusions. Safety outcomes included the incidence of adverse events and antipanitumumab antibody formation. Pharmacokinetic properties were determined. Efficacy endpoints included response rate and duration of response. Results: Eighty-six patients were enrolled; 84 (98%) received panitumumab. Treatment-related adverse events occurred in 90% of patients. Safety profiles were similar between patients receiving 30-minute (n = 20) and 60-minute (n = 43) infusions every 2 weeks and patients receiving panitumumab every 3 weeks (n = 21). Panitumumab exposure at steady state increased dose proportionally, and peak serum concentrations were similar in patients receiving either 30- or 60-minute infusions every 2 weeks. Objective responses were seen in 4 patients (5%) with colon, rectal, esophageal, and bladder cancers. Conclusion: Similar drug exposures and safety profiles were observed in patients receiving panitumumab 6 mg/kg every 2 weeks with either 30- or 60-minute infusions and antitumor activity was seen in some patients. Exposure increased approximately dose proportionally at steady state.

Authors
Stephenson, JJ; Gregory, C; Burris, H; Larson, T; Verma, U; Cohn, A; Crawford, J; Cohen, RB; Martin, J; Lum, P; Yang, X; Amado, RG
MLA Citation
Stephenson, JJ, Gregory, C, Burris, H, Larson, T, Verma, U, Cohn, A, Crawford, J, Cohen, RB, Martin, J, Lum, P, Yang, X, and Amado, RG. "An open-label clinical trial evaluating safety and pharmacokinetics of two dosing schedules of panitumumab in patients with solid tumors." Clinical Colorectal Cancer 8.1 (2009): 29-37.
PMID
19203894
Source
scival
Published In
Clinical colorectal cancer
Volume
8
Issue
1
Publish Date
2009
Start Page
29
End Page
37
DOI
10.3816/CCC.2009.n.005

Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study.

BACKGROUND: A feasibility study examining the effects of supervised aerobic exercise training on cardiopulmonary and quality of life (QOL) endpoints among postsurgical nonsmall cell lung cancer (NSCLC) patients was conducted. METHODS: Using a single-group design, 20 patients with stage I-IIIB NSCLC performed 3 aerobic cycle ergometry sessions per week at 60% to 100% of peak workload for 14 weeks. Peak oxygen consumption (VO(2peak)) was assessed using an incremental exercise test. QOL and fatigue were assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale. RESULTS: Nineteen patients completed the study. Intention-to-treat analysis indicated that VO(2peak) increased 1.1 mL/kg(-1)/min(-1) (95% confidence interval [CI], -0.3-2.5; P = .109) and peak workload increased 9 W (95% CI, 3-14; P = .003), whereas FACT-L increased 10 points (95% CI, -1-22; P = .071) and fatigue decreased 7 points (95% CI; -1 to -17; P = .029) from baseline to postintervention. Per protocol analyses indicated greater improvements in cardiopulmonary and QOL endpoints among patients not receiving adjuvant chemotherapy. CONCLUSIONS: This pilot study provided proof of principle that supervised aerobic training is safe and feasible for postsurgical NSCLC patients. Aerobic exercise training is also associated with significant improvements in QOL and select cardiopulmonary endpoints, particularly among patients not receiving chemotherapy. Larger randomized trials are warranted.

Authors
Jones, LW; Eves, ND; Peterson, BL; Garst, J; Crawford, J; West, MJ; Mabe, S; Harpole, D; Kraus, WE; Douglas, PS
MLA Citation
Jones, LW, Eves, ND, Peterson, BL, Garst, J, Crawford, J, West, MJ, Mabe, S, Harpole, D, Kraus, WE, and Douglas, PS. "Safety and feasibility of aerobic training on cardiopulmonary function and quality of life in postsurgical nonsmall cell lung cancer patients: a pilot study." Cancer 113.12 (December 15, 2008): 3430-3439.
PMID
18988290
Source
pubmed
Published In
Cancer
Volume
113
Issue
12
Publish Date
2008
Start Page
3430
End Page
3439
DOI
10.1002/cncr.23967

Formation of a bronchoesophageal fistula following concurrent radiation and chemotherapy for lung cancer in the setting of Behçet's disease.

Authors
Meyer, J; Wahidi, M; Shofer, S; Evans, J; Crawford, J; Kelsey, CR
MLA Citation
Meyer, J, Wahidi, M, Shofer, S, Evans, J, Crawford, J, and Kelsey, CR. "Formation of a bronchoesophageal fistula following concurrent radiation and chemotherapy for lung cancer in the setting of Behçet's disease." J Thorac Oncol 3.11 (November 2008): 1361-1362. (Letter)
PMID
18978575
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
3
Issue
11
Publish Date
2008
Start Page
1361
End Page
1362
DOI
10.1097/JTO.0b013e31818b1af2

Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice.

This study was undertaken to describe the relationship between the occurrence and timing of neutropenic events and chemotherapy treatment in a community-based population of patients with cancer. The study included 2962 patients with breast, lung, colorectal, lymphoma, and ovarian cancers from a prospective U.S. registry of patients initiating a new chemotherapy regimen. Detailed patient-, disease-, and treatment-related data, including toxicities, were captured at baseline, the beginning of each cycle, and each midcycle blood draw for up to 4 cycles of treatment. Primary outcomes included febrile neutropenia (FN), severe neutropenia without fever/ infection, and relative dose intensity (RDI). Thirty-seven percent of patients were aged 65 years or older, 43.5% had an Eastern Cooperative Oncology Group performance status of 1 or greater, and 27% had 1 or more comorbidities. Reductions in RDI to less than 85% of standard in the first cycle were planned in 23.6% of patients, whereas primary colony-stimulating factor prophylaxis was used in 18.2%. In the first 3 cycles of treatment, 10.7% of patients experienced FN, with most of these events (58.9%) occurring in the first cycle. This first-cycle pattern was consistently observed despite wide variations in event rates by tumor type, disease stage, chemotherapy regimen and dose, and patient characteristics. Despite frequent planned reductions from standard RDI, the incidence of FN remains high in community oncology practice in the United States. Improved methods of pretreatment assessment of patient risk factors for neutropenia are needed.

Authors
Crawford, J; Dale, DC; Kuderer, NM; Culakova, E; Poniewierski, MS; Wolff, D; Lyman, GH
MLA Citation
Crawford, J, Dale, DC, Kuderer, NM, Culakova, E, Poniewierski, MS, Wolff, D, and Lyman, GH. "Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice." J Natl Compr Canc Netw 6.2 (February 2008): 109-118.
PMID
18319047
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
2
Publish Date
2008
Start Page
109
End Page
118

Phase 2 study of mapatumumab, a fully human agonistic monoclonal antibody which targets and activates the TRAIL receptor-1, in patients with advanced non-small cell lung cancer

Background: Preclinical pharmacological properties of mapatumumab (agonistic human monoclonal antibody to TRAIL-R1) suggest that this antibody reduces cell viability, induces cell death in many types of cancer cell lines in vitro, inhibits or reduces tumor growth in xenograft models of solid tumors, and can induce significant tumor regression in some models. The receptor for mapatumumab, TRAIL-R1, is expressed on NSCLC cell lines. This pharmacologic profile suggests that mapatumumab may have therapeutic benefit in the treatment of NSCLC. Methods: This Phase 2 multi-center study was designed to evaluate the efficacy, safety, and tolerability of mapatumumab in patients with advanced non-small cell lung cancer (NSCLC) previously treated with at least 1 platinum-based regimen. Each patient was to receive mapatumumab at a dose of 10 mg/kg administered intravenously (IV) every 21 days in absence of disease progression. Results: A total of 32 patients with relapsed or refractory Stage IIIB or IV or recurrent NSCLC were enrolled. Patients had received a median of 3 previous therapeutic regimens (range 1-7). Mapatumumab was well tolerated by the patients in this study with no discontinuations due to adverse events. The most common adverse events reported, regardless of relationship, were fatigue, cough, nausea, dyspnea, constipation, and vomiting. Laboratory analyses revealed no appreciable evidence of hepatic or renal toxicity among the study patients. No patients developed anti-mapatumumab antibodies. The plasma mapatumumab concentrations observed in this study were consistent with the predicted exposures, based on Phase 1 pharmacokinetic results. None of the 32 treated patients showed a response according to the RECIST criteria. Nine patients (29%) had stable disease (SD). Conclusion: In a group of heavily pretreated NSCLC patients, no objective single agent activity of mapatumumab was demonstrated, but the drug was safe and well tolerated. Based on this favorable safety profile, and preclinical evidence of potential synergy in combination with agents commonly used to treat NSCLC, future evaluation of mapatumumab in combination with chemotherapy is warranted. © 2008 Elsevier Ireland Ltd. All rights reserved.

Authors
Greco, FA; Bonomi, P; Crawford, J; Kelly, K; Oh, Y; Halpern, W; Lo, L; Gallant, G; Klein, J
MLA Citation
Greco, FA, Bonomi, P, Crawford, J, Kelly, K, Oh, Y, Halpern, W, Lo, L, Gallant, G, and Klein, J. "Phase 2 study of mapatumumab, a fully human agonistic monoclonal antibody which targets and activates the TRAIL receptor-1, in patients with advanced non-small cell lung cancer." Lung Cancer 61.1 (2008): 82-90.
PMID
18255187
Source
scival
Published In
Lung Cancer
Volume
61
Issue
1
Publish Date
2008
Start Page
82
End Page
90
DOI
10.1016/j.lungcan.2007.12.011

Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies

Purpose: This phase 1 study evaluated the safety, pharmacokinetics, and activity of panitumumab, a fully human, IgG2 monoclonal antibody that targets the epidermal growth factor receptor in patients with previously treated epidermal growth factor receptor - expressing advanced solid tumors. Experimental Design: Sequential cohorts were enrolled to receive four i.v. infusions of panitumumab monotherapy at various doses and schedules. Safety was continuously monitored. Serum samples for pharmacokinetic, immunogenicity, and chemistry assessments were drawn at preset intervals. Tumor response was assessed at week 8. Results: Ninety-six patients received panitumumab. Median (range) age was 61 years (32-79 years), and 72 (75%) patients were male. Tumor types were 41% colorectal cancer, 22% prostate, 16% renal, 15% non-small cell lung, 3% pancreatic, 3% esophageal/gastroesophageal, and 1% anal. The overall incidence of grade 3 or 4 adverse events was 32% and 7%, respectively. The incidence of skin-related toxicities was dose dependent. No maximum tolerated dose was reached. No human anti-panitumumab antibodies were detected. No investigator-determined panitumumab infusion-related reactions were reported. Serum panitumumab concentrations were similar in the 2.5 mg/kg weekly, 6.0 mg/kg every 2 weeks, and 9.0 mg/kg every 3 weeks dose cohorts. Five of 39 patients (13%) with colorectal cancer had a confirmed partial response, and 9 of 39 patients (23%) with colorectal cancer had stable disease. Conclusions: Panitumumab was well tolerated with comparable exposure and safety profiles for the weekly, every 2 weeks, and every 3 weeks administration schedules. Rash and dry skin occurred more frequently in the dose cohorts receiving ≥2.5 mg/kg weekly dose. Panitumumab has single-agent antitumor activity, most notably in patients with advanced colorectal cancer. © 2008 American Association for Cancer Research.

Authors
Weiner, LM; Belldegrun, AS; Crawford, J; Tolcher, AW; Lockbaum, P; Arends, RH; Navale, L; Amado, RG; Schwab, G; Figlin, RA
MLA Citation
Weiner, LM, Belldegrun, AS, Crawford, J, Tolcher, AW, Lockbaum, P, Arends, RH, Navale, L, Amado, RG, Schwab, G, and Figlin, RA. "Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies." Clinical Cancer Research 14.2 (2008): 502-508.
PMID
18223225
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
14
Issue
2
Publish Date
2008
Start Page
502
End Page
508
DOI
10.1158/1078-0432.CCR-07-1509

Dose intensity and hematologic toxicity in older cancer patients receiving systemic chemotherapy.

BACKGROUND: This prospective study was undertaken to evaluate patient and treatment characteristics that contribute to hematologic toxicity in older cancer patients. METHODS: A nationwide study of 115 community oncology practices was conducted between 2002 and 2005 with data collected on 976 patients who had received chemotherapy for common malignancies, including lung cancer, colorectal cancer, breast cancer, ovarian cancer, genitourinary cancer, and lymphoma. Primary outcomes included severe neutropenia (SN) and febrile neutropenia (FN). Secondary outcomes included delivered relative dose intensity (RDI) <85%, dose delays > or =15% days, and reductions > or =15%. RESULTS: Approximately 50% of both patients with early-stage disease and patients with advanced-stage disease received an actual RDI <85%, and this rate reached 60% in the oldest group (aged >80 years). Increasing age was associated with lower actual RDI (P = .030) and averaged 87.5% across all elderly age groups. A decreasing trend in SN or FN events occurred with increasing age (P for trend = .039), with the majority of initial neutropenic events occurring in Cycle 1 for all age groups. Among the patients who received an actual RDI > OR =85%, there was no significant difference in SN or FN by age group or disease stage. Independent risk factors for the development of SN or FN included cancer type, planned RDI > or =85%, body surface area < or =2m(2), anthracycline- or platinum-based regimens, previous chemotherapy, elevated blood urea nitrogen, and alkaline phosphatase. Neutropenic complications decreased significantly with primary colony-stimulating factor (CSF) prophylaxis (coefficient of determination [R(2)] = 0.260; c-statistic = 0.782). CONCLUSIONS: Among cancer patients aged > or =70 years, 50% of whom received relatively full-dose chemotherapy, increasing age alone did not increase the risk of hematologic toxicity.

Authors
Shayne, M; Culakova, E; Poniewierski, MS; Wolff, D; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Shayne, M, Culakova, E, Poniewierski, MS, Wolff, D, Dale, DC, Crawford, J, and Lyman, GH. "Dose intensity and hematologic toxicity in older cancer patients receiving systemic chemotherapy." Cancer 110.7 (October 1, 2007): 1611-1620.
PMID
17705197
Source
pubmed
Published In
Cancer
Volume
110
Issue
7
Publish Date
2007
Start Page
1611
End Page
1620
DOI
10.1002/cncr.22939

Hitting our stride.

Authors
Crawford, J
MLA Citation
Crawford, J. "Hitting our stride." Support Cancer Ther 4.4 (September 1, 2007): 178-179.
PMID
18632514
Source
pubmed
Published In
Supportive cancer therapy
Volume
4
Issue
4
Publish Date
2007
Start Page
178
End Page
179
DOI
10.3816/SCT.2007.n.012

Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review.

PURPOSE: Randomized controlled trials (RCTs) of prophylactic granulocyte colony-stimulating factors (G-CSF) have demonstrated a significant reduction in febrile neutropenia (FN) after systemic chemotherapy. Several RCTs have been published recently that investigate the impact of G-CSF on mortality and relative dose-intensity (RDI). METHODS: A comprehensive systematic review and meta-analysis of all reported RCTs comparing primary prophylactic G-CSF with placebo or untreated controls in adult solid tumor and malignant lymphoma patients was undertaken without language restrictions, using electronic databases, conference proceedings, and hand-searching techniques. Two reviewers extracted data independently. Summary estimates of relative risk (RR) with 95% CIs were estimated based on the method of Mantel-Haenszel and DerSimonian and Laird. RESULTS: Seventeen RCTs were identified including 3,493 patients. For infection-related mortality, RR reduction with G-CSF compared with controls was 45% (RR = 0.55; 95% CI, 0.33 to 0.90; P = .018); for early mortality (all-cause mortality during chemotherapy period), it was 40% (RR = 0.60; 95% CI, 0.43 to 0.83; P = .002); and for FN, it was 46% (RR = 0.54; 95% CI, 0.43 to 0.67; P < .001). Average RDI was significantly higher in patients who received G-CSF compared with control patients (P < .001). Bone or musculoskeletal pain was reported in 10.4% of controls and 19.6% of G-CSF patients (RR = 4.03; 95% CI, 2.15 to 7.52; P < .001). Significant reductions in FN with G-CSF were observed in studies allowing secondary G-CSF prophylaxis in controls and in the three trials with concurrent prophylactic antibiotics in both treatment arms. CONCLUSION: Prophylactic G-CSF reduces the risk of FN and early deaths, including infection-related mortality, while increasing RDI and musculoskeletal pain. There are insufficient data to assess the impact of G-CSF on disease-free and overall survival.

Authors
Kuderer, NM; Dale, DC; Crawford, J; Lyman, GH
MLA Citation
Kuderer, NM, Dale, DC, Crawford, J, and Lyman, GH. "Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review." J Clin Oncol 25.21 (July 20, 2007): 3158-3167. (Review)
PMID
17634496
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
21
Publish Date
2007
Start Page
3158
End Page
3167
DOI
10.1200/JCO.2006.08.8823

Social and racial differences in selection of breast cancer adjuvant chemotherapy regimens.

PURPOSE: Breast cancer outcomes are worse among black women and women of lower socioeconomic status. The purpose of this study was to investigate racial and social differences in selection of breast cancer adjuvant chemotherapy regimens. METHODS: Detailed information on patient, disease, and treatment factors was collected prospectively on 957 patients who were receiving breast cancer adjuvant chemotherapy in 101 oncology practices throughout the United States. Adjuvant chemotherapy regimens included in any of several published guidelines were considered standard. Receipt of nonstandard regimens was examined according to clinical and nonclinical factors. Differences between groups were assessed using chi2 tests. Multivariate logistic regression was used to identify factors associated with use of nonstandard regimens. RESULTS: Black race (P = .008), lower educational attainment (P = .003), age 70 years (P = .001), higher stage (P < .0001), insurance type (P = .048), employment status (P = .045), employment type (P = .025), and geographic location (P = .021) were associated with the use of nonstandard regimens in univariate analyses. In multivariate analysis, black race (P = .020), lower educational attainment (P = .024), age > or = 70 years (P = .032), and higher stage (P < .0001) were associated with receipt of nonstandard regimens. CONCLUSION: The more frequent use of non-guideline-concordant adjuvant chemotherapy regimens in black women and women with lower educational attainment may contribute to less favorable outcomes in these populations. Addressing such differences in care may improve cancer outcomes in vulnerable populations.

Authors
Griggs, JJ; Culakova, E; Sorbero, MES; Poniewierski, MS; Wolff, DA; Crawford, J; Dale, DC; Lyman, GH
MLA Citation
Griggs, JJ, Culakova, E, Sorbero, MES, Poniewierski, MS, Wolff, DA, Crawford, J, Dale, DC, and Lyman, GH. "Social and racial differences in selection of breast cancer adjuvant chemotherapy regimens." J Clin Oncol 25.18 (June 20, 2007): 2522-2527.
PMID
17577029
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
18
Publish Date
2007
Start Page
2522
End Page
2527
DOI
10.1200/JCO.2006.10.2749

A phase II trial of carboplatin/vinorelbine with pegfilgrastim support for the treatment of patients with advanced non-small cell lung cancer.

INTRODUCTION: The impact of chemotherapy dose delivery has not been well studied in patients with non-small cell lung cancer (NSCLC). Overlapping hematologic toxicities commonly limit planned dose intensity of combination chemotherapy regimens. A phase II study investigating carboplatin and vinorelbine, supported by pegfilgrastim, in the treatment of patients with advanced NSCLC was performed. METHODS: Chemotherapy-naïve patients with locally advanced or metastatic NSCLC were treated with carboplatin area under the curve (AUC) 6 mg/ml per minute intravenously on day 1 and vinorelbine 30 mg/m2 intravenously on days 1 and 8 every 3 weeks for four planned cycles. Pegfilgrastim was administered on day 9 of each cycle as a 6-mg subcutaneous injection. The primary endpoint was incidence of cycle 1 febrile neutropenia. Secondary endpoints included incidence of grade 3/4 hematologic and nonhematologic toxicities, delivered dose intensity, and overall survival. RESULTS: Thirty patients (21 men, 9 women) with a median age of 61 years (range, 43-79) were enrolled. Of 120 planned patient cycles, 101 (84%) were completed. There was one episode of cycle 1 febrile neutropenia. Overall response rate was 27%. Median dose delivered for vinorelbine was 17.2 mg/m2 per week, representing a delivered dose intensity of 86%. Median survival was 9.4 months (95% confidence interval: 6.1-18.0) with a 3-year survival rate of 20%. CONCLUSIONS: This regimen of carboplatin and vinorelbine with pegfilgrastim support was associated with a low rate of febrile neutropenia and good maintenance of planned dose intensity. Although response and survival are similar to other chemotherapy regimens in advanced NSCLC, studies optimizing chemotherapy delivery in this setting may help inform treatment approaches in patients with earlier stage disease.

Authors
Riedel, RF; Andrews, C; Garst, J; Dunphy, F; Herndon, JE; Blackwell, S; Barbour, S; Crawford, J
MLA Citation
Riedel, RF, Andrews, C, Garst, J, Dunphy, F, Herndon, JE, Blackwell, S, Barbour, S, and Crawford, J. "A phase II trial of carboplatin/vinorelbine with pegfilgrastim support for the treatment of patients with advanced non-small cell lung cancer." J Thorac Oncol 2.6 (June 2007): 520-525.
PMID
17545847
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
2
Issue
6
Publish Date
2007
Start Page
520
End Page
525
DOI
10.1097/JTO.0b013e318060107c

May day.

Authors
Crawford, J
MLA Citation
Crawford, J. "May day." Support Cancer Ther 4.3 (May 1, 2007): 135-136.
PMID
18632478
Source
pubmed
Published In
Supportive cancer therapy
Volume
4
Issue
3
Publish Date
2007
Start Page
135
End Page
136
DOI
10.3816/SCT.2007.n.007

A randomized trial comparing immediate versus delayed treatment of anemia with once-weekly epoetin alfa in patients with non-small cell lung cancer scheduled to receive first-line chemotherapy.

INTRODUCTION: This study evaluated the safety/efficacy of once-weekly (QW) epoetin alfa measured by quality of life (QOL), hemoglobin (Hb), transfusion incidence, tumor response, and survival in patients with chemotherapy-naïve, advanced non-small cell lung cancer (NSCLC). METHODS: Stage IIIB/IV NSCLC patients with Hb > or = 11 to < 15 g/dl scheduled for at least 8 weeks of first-line chemotherapy were randomized to subcutaneously receive 40,000 U of epoetin alfa QW at chemotherapy initiation (immediate) or no epoetin alfa unless Hb decreased to < or = 10 g/dl (delayed). The primary efficacy variable was change in QOL for immediate versus delayed intervention. Target accrual was 320 patients. RESULTS: The study was terminated early because of slow accrual; of 216 patients enrolled, 211 were evaluable for efficacy. Hb was maintained in the immediate group, but it decreased in the delayed group (12.9 versus 11.6 g/dl final values, respectively). Numerically, fewer immediate patients required transfusions versus delayed patients. Mean QOL scores, modestly declining in both groups from baseline to final measurement, were not significantly different between groups. Tumor response and median overall survival were similar between groups. Epoetin alfa was well tolerated, with a similar thrombovascular event rate between groups. CONCLUSION: Epoetin alfa in subcutaneous doses of 40,000 U QW, given immediately at chemotherapy initiation for advanced NSCLC, was well tolerated, and it effectively maintained Hb, leading to a reduced transfusion incidence versus delayed epoetin alfa. Overall QOL scores were higher than typical in this population, decreasing slightly during treatment in both groups. Overall survival was similar between groups, with no evidence of a negative effect by early epoetin alfa intervention.

Authors
Crawford, J; Robert, F; Perry, MC; Belani, C; Williams, D; Anemia Prevention in NSCLC Group,
MLA Citation
Crawford, J, Robert, F, Perry, MC, Belani, C, Williams, D, and Anemia Prevention in NSCLC Group, . "A randomized trial comparing immediate versus delayed treatment of anemia with once-weekly epoetin alfa in patients with non-small cell lung cancer scheduled to receive first-line chemotherapy." J Thorac Oncol 2.3 (March 2007): 210-220.
PMID
17410044
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
2
Issue
3
Publish Date
2007
Start Page
210
End Page
220
DOI
10.1097/JTO.0b013e318031cd9a

Myeloid growth factors. Clinical practice guidelines in oncology.

Authors
Crawford, J; Althaus, B; Armitage, J; Balducci, L; Bennett, C; Blayney, DW; Cataland, SR; Dale, DC; Demetri, GD; Erba, HP; Foran, J; Freifeld, AG; Heaney, ML; Htoy, S; Kloth, DD; Lyman, GH; Messersmith, WA; Michaud, LB; Miyata, SC; Robbins, A; Tallman, MS; Vadhan-Raj, S; Westervelt, P; Wong, MK; National Comprehensive Cancer Network (NCCN),
MLA Citation
Crawford, J, Althaus, B, Armitage, J, Balducci, L, Bennett, C, Blayney, DW, Cataland, SR, Dale, DC, Demetri, GD, Erba, HP, Foran, J, Freifeld, AG, Heaney, ML, Htoy, S, Kloth, DD, Lyman, GH, Messersmith, WA, Michaud, LB, Miyata, SC, Robbins, A, Tallman, MS, Vadhan-Raj, S, Westervelt, P, Wong, MK, and National Comprehensive Cancer Network (NCCN), . "Myeloid growth factors. Clinical practice guidelines in oncology." J Natl Compr Canc Netw 5.2 (February 2007): 188-202.
PMID
17335688
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
5
Issue
2
Publish Date
2007
Start Page
188
End Page
202

Effect of patient socioeconomic status and body mass index on the quality of breast cancer adjuvant chemotherapy.

PURPOSE: The purpose of this study was to investigate the relationship between socioeconomic status (SES) and the use of intentionally reduced doses of chemotherapy in the adjuvant treatment of breast cancer. PATIENTS AND METHODS: Patients with breast cancer treated with a standard chemotherapy regimen (n = 764) were enrolled in a prospective registry after signing informed consent. Detailed information was collected on patient, disease, and treatment, including chemotherapy doses. Zip code level data on median household income, proportion of people living below the poverty level, and educational attainment were obtained from the US Census. Doses for the first cycle of chemotherapy lower than 85% of standard were considered to be reduced. Univariate analyses and multivariate logistic regression were performed to identify factors associated with the use of reduced first cycle doses. RESULTS: In univariate analysis, individual education attainment, zip code SES measures, body mass index, and geographic region were all significantly associated with receipt of intentionally reduced doses of chemotherapy. In multivariate analysis, controlling for geography, factors independently associated with reduced doses were obesity (odds ratio [OR], 2.47; 95% CI, 1.36 to 4.51), severe obesity (OR, 4.04; 95% CI, 1.46 to 11.19), and education less than high school (OR, 3.07; 95% CI, 1.57 to 5.99). CONCLUSION: Social disparities in breast cancer outcomes may be in part the result of lower quality chemotherapy doses in the adjuvant treatment of breast cancer. Efforts to address such prescribing patterns may help reduce SES disparities in breast cancer survival.

Authors
Griggs, JJ; Culakova, E; Sorbero, MES; van Ryn, M; Poniewierski, MS; Wolff, DA; Crawford, J; Dale, DC; Lyman, GH
MLA Citation
Griggs, JJ, Culakova, E, Sorbero, MES, van Ryn, M, Poniewierski, MS, Wolff, DA, Crawford, J, Dale, DC, and Lyman, GH. "Effect of patient socioeconomic status and body mass index on the quality of breast cancer adjuvant chemotherapy." J Clin Oncol 25.3 (January 20, 2007): 277-284.
PMID
17159190
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
3
Publish Date
2007
Start Page
277
End Page
284
DOI
10.1200/JCO.2006.08.3063

Cancer management in the era of targeted agents.

Authors
Crawford, J
MLA Citation
Crawford, J. "Cancer management in the era of targeted agents." Support Cancer Ther 4.2 (January 1, 2007): 69-.
PMID
18632470
Source
pubmed
Published In
Supportive cancer therapy
Volume
4
Issue
2
Publish Date
2007
Start Page
69
DOI
10.3816/SCT.2007.n.001

Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective.

BACKGROUND: The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) reduces the severity and duration of neutropenia and reduces the incidence of febrile neutropenia after cancer chemotherapy. However, the use of G-CSFs, particularly filgrastim, to treat established neutropenia remains controversial. A recent meta-analysis of randomised controlled trials (RCTs) evaluating G-CSF treatment for established febrile neutropenia demonstrated a reduction in prolonged hospitalisations. Because more than one-third of patients in the analysis were hospitalised for at least 10 days, this finding has broad pharmacoeconomic and clinical significance. This analysis presents the potential cost implications of G-CSF treatment for established neutropenia among hospitalised patients. METHODS: Direct medical costs ($US, year 2003 values) related to hospitalisation for established neutropenia were modelled using a hospital perspective and according to two treatment options: (i) no use of G-CSF during the neutropenic episode (control); and (ii) addition of daily G-CSF until neutrophil recovery. Within each option, we modelled the probability of a long stay (>or=10 days) and patient survival. The model used three data sets: discharge data from a consortium of academic medical institutions, drug cost data (filgrastim) from Federal payers, and estimates of G-CSF efficacy derived from a meta-analysis of RCTs of treatment in patients with established febrile neutropenia. The lowest expected total cost was predicted for both treatment options; sensitivity analyses and Monte Carlo simulations were used to evaluate the robustness of the model. RESULTS: The G-CSF arm produced the lowest expected cost, and predicted net estimated savings of $US1046 per neutropenic episode compared with the control strategy. G-CSF was less expensive than the control for most reasonable estimates of cost per day and all lengths of stay (LOS) >or=10 days. G-CSF was the least costly strategy for 73.5% of 10,000 Monte Carlo iterations, while the no-G-CSF control strategy predicted savings in 26.5% of iterations. CONCLUSIONS: This pharmacoeconomic model suggests that therapeutic use of G-CSF should be considered for patients with established neutropenia in order to reduce overall hospital cost. G-CSF treatment may offer substantial potential savings for hospitalised patients with established neutropenia over a wide range of model assumptions. Therapeutic G-CSF use among patients hospitalised for established neutropenia may complement the recommended prophylactic use of these agents for the prevention of neutropenic episodes.

Authors
Cosler, LE; Eldar-Lissai, A; Culakova, E; Kuderer, NM; Dale, D; Crawford, J; Lyman, GH
MLA Citation
Cosler, LE, Eldar-Lissai, A, Culakova, E, Kuderer, NM, Dale, D, Crawford, J, and Lyman, GH. "Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective." Pharmacoeconomics 25.4 (2007): 343-351.
PMID
17402806
Source
pubmed
Published In
PharmacoEconomics
Volume
25
Issue
4
Publish Date
2007
Start Page
343
End Page
351

Erythropoietin: High profile, high scrutiny

Authors
Crawford, J
MLA Citation
Crawford, J. "Erythropoietin: High profile, high scrutiny." Journal of Clinical Oncology 25.9 (2007): 1021-1023.
PMID
17312331
Source
scival
Published In
Journal of Clinical Oncology
Volume
25
Issue
9
Publish Date
2007
Start Page
1021
End Page
1023
DOI
10.1200/JCO.2006.08.8153

Update on neutropenia and myeloid growth factors

Authors
Crawford, J
MLA Citation
Crawford, J. "Update on neutropenia and myeloid growth factors." Journal of Supportive Oncology 5.4 SUPPL. 2 (2007): 27-29.
PMID
17550054
Source
scival
Published In
The Journal of Supportive Oncology
Volume
5
Issue
4 SUPPL. 2
Publish Date
2007
Start Page
27
End Page
29

Controlling symptoms in elderly lung cancer patients

Authors
Crawford, J
MLA Citation
Crawford, J. "Controlling symptoms in elderly lung cancer patients." Journal of Supportive Oncology 5.2 (2007): 78-79.
PMID
17348364
Source
scival
Published In
The Journal of Supportive Oncology
Volume
5
Issue
2
Publish Date
2007
Start Page
78
End Page
79

A phase II study of eltrombopag in the treatment of thrombocytopenia in patients with relapsed/refractory idiopathic thrombocytopenic purpura

Authors
Reddy, GK; Shivakumar, L; Muneer, S; Crawford, J
MLA Citation
Reddy, GK, Shivakumar, L, Muneer, S, and Crawford, J. "A phase II study of eltrombopag in the treatment of thrombocytopenia in patients with relapsed/refractory idiopathic thrombocytopenic purpura." Supportive Cancer Therapy 4.2 (2007): 73-74.
Source
scival
Published In
Supportive cancer therapy
Volume
4
Issue
2
Publish Date
2007
Start Page
73
End Page
74

Long-term analysis of the safety and tolerability of the oral iron chelator deferasirox in patients with transfusional iron overload

Authors
Reddy, GK; Shivakumar, L; Muneer, S; Crawford, J
MLA Citation
Reddy, GK, Shivakumar, L, Muneer, S, and Crawford, J. "Long-term analysis of the safety and tolerability of the oral iron chelator deferasirox in patients with transfusional iron overload." Supportive Cancer Therapy 4.2 (2007): 75-77.
Source
scival
Published In
Supportive cancer therapy
Volume
4
Issue
2
Publish Date
2007
Start Page
75
End Page
77

Preliminary results of a phase II dose-finding study of subcutaneous Hematide™ in patients with cancer receiving chemotherapy

Authors
Reddy, GK; Shivakumar, L; Muneer, S; Crawford, J
MLA Citation
Reddy, GK, Shivakumar, L, Muneer, S, and Crawford, J. "Preliminary results of a phase II dose-finding study of subcutaneous Hematide™ in patients with cancer receiving chemotherapy." Supportive Cancer Therapy 4.2 (2007): 74-75.
Source
scival
Published In
Supportive cancer therapy
Volume
4
Issue
2
Publish Date
2007
Start Page
74
End Page
75

Long-term effects of the novel thrombopoietic agent AMG-531 in patients with immune thrombocytopenic purpura

Authors
Reddy, GK; Shivakumar, L; Muneer, S; Crawford, J
MLA Citation
Reddy, GK, Shivakumar, L, Muneer, S, and Crawford, J. "Long-term effects of the novel thrombopoietic agent AMG-531 in patients with immune thrombocytopenic purpura." Supportive Cancer Therapy 4.2 (2007): 72-73.
Source
scival
Published In
Supportive cancer therapy
Volume
4
Issue
2
Publish Date
2007
Start Page
72
End Page
73

Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy.

BACKGROUND: This retrospective study was undertaken to define risk factors for reductions in dose intensity of adjuvant chemotherapy in women with early stage breast cancer (ESBC). METHODS: A nationwide survey of 190 community oncology practices was conducted between 1998 and 2002 with data collected retrospectively on 3,707 patients treated with adjuvant chemotherapy for ESBC. End points included reductions in dose intensity, delivered relative dose intensity (RDI) <85%, and the incidence of chemotherapy dose delays >/=7 days and dose reduction >/=15%. Demographic and clinical characteristics, incidence of febrile neutropenia (FN), and patterns of use of granulocyte colony-stimulating factor (G-CSF) were also assessed. RESULTS: Average RDI for all regimens was 88%, with 30% of patients receiving <85% of standard for their regimen. Seventeen percent of the reduction in average RDI was planned from the start of therapy, and 13% was unplanned. In univariate analysis, significant predictors of reduced RDI were: age >/=65 years (41%, P < 0.001), body surface area (BSA) >2 m(2) (37%, P < 0.001), negative lymph nodes (33%, P < 0.001), FN (36%, P = 0.013), and comorbidities (40%, P = 0.013), particularly renal disease (86%, P = 0.004). Dose reduction was less with prophylactic G-CSF (24%, P < 0.001). In multivariate analysis, significant independent predictors of reduced RDI included: advanced age, greater BSA, comorbidities, anthracycline-based regimens, a 28-day schedule and FN, while primary G-CSF prophylaxis was associated with a significant reduction in risk. CONCLUSION: A significant proportion of patients with potentially curable ESBC continue to experience planned and unplanned reductions in RDI.

Authors
Shayne, M; Crawford, J; Dale, DC; Culakova, E; Lyman, GH; ANC Study Group,
MLA Citation
Shayne, M, Crawford, J, Dale, DC, Culakova, E, Lyman, GH, and ANC Study Group, . "Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy." Breast Cancer Res Treat 100.3 (December 2006): 255-262.
PMID
16705366
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
100
Issue
3
Publish Date
2006
Start Page
255
End Page
262
DOI
10.1007/s10549-006-9254-4

Phase II study of carboplatin, irinotecan, and thalidomide combination in patients with extensive stage small-cell lung cancer.

Authors
Riedel, RF; Crawford, J; Dunphy, F; Herndon, JE; Garst, J; Kelley, MJ
MLA Citation
Riedel, RF, Crawford, J, Dunphy, F, Herndon, JE, Garst, J, and Kelley, MJ. "Phase II study of carboplatin, irinotecan, and thalidomide combination in patients with extensive stage small-cell lung cancer." Lung Cancer 54.3 (December 2006): 431-432. (Letter)
PMID
17005294
Source
pubmed
Published In
Lung Cancer
Volume
54
Issue
3
Publish Date
2006
Start Page
431
End Page
432
DOI
10.1016/j.lungcan.2006.08.008

Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury.

PURPOSE: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. METHODS AND MATERIALS: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status>or=70, and life expectancy>or=6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m2) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. RESULTS: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. CONCLUSIONS: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity.

Authors
Anscher, MS; Garst, J; Marks, LB; Larrier, N; Dunphy, F; Herndon, JE; Clough, R; Marino, C; Vujaskovic, Z; Zhou, S; Dewhirst, MW; Shafman, TD; Crawford, J
MLA Citation
Anscher, MS, Garst, J, Marks, LB, Larrier, N, Dunphy, F, Herndon, JE, Clough, R, Marino, C, Vujaskovic, Z, Zhou, S, Dewhirst, MW, Shafman, TD, and Crawford, J. "Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury." Int J Radiat Oncol Biol Phys 66.2 (October 1, 2006): 477-482.
PMID
16904841
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
2
Publish Date
2006
Start Page
477
End Page
482
DOI
10.1016/j.ijrobp.2006.05.031

Disease management and patient-reported outcomes.

Authors
Crawford, J
MLA Citation
Crawford, J. "Disease management and patient-reported outcomes." Support Cancer Ther 4.1 (October 1, 2006): 14-.
PMID
18632460
Source
pubmed
Published In
Supportive cancer therapy
Volume
4
Issue
1
Publish Date
2006
Start Page
14
DOI
10.3816/SCT.2006.n.025

EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours.

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (>or=65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10-20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.

Authors
Aapro, MS; Cameron, DA; Pettengell, R; Bohlius, J; Crawford, J; Ellis, M; Kearney, N; Lyman, GH; Tjan-Heijnen, VC; Walewski, J; Weber, DC; Zielinski, C; European Organisation for Research and Treatment of Cancer (EORTC) Granulocyte Colony-Stimulating Factor (G-CSF) Guidelines Working Party,
MLA Citation
Aapro, MS, Cameron, DA, Pettengell, R, Bohlius, J, Crawford, J, Ellis, M, Kearney, N, Lyman, GH, Tjan-Heijnen, VC, Walewski, J, Weber, DC, Zielinski, C, and European Organisation for Research and Treatment of Cancer (EORTC) Granulocyte Colony-Stimulating Factor (G-CSF) Guidelines Working Party, . "EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours." Eur J Cancer 42.15 (October 2006): 2433-2453. (Review)
PMID
16750358
Source
pubmed
Published In
European Journal of Cancer
Volume
42
Issue
15
Publish Date
2006
Start Page
2433
End Page
2453
DOI
10.1016/j.ejca.2006.05.002

Targeting anemia in patients with lung cancer.

Anemia is highly prevalent in patients with lung cancer, often occurring at baseline and frequently exacerbated as a result of treatment with platinum-based chemotherapy. Anemia has been shown to have a negative effect on quality of life in patients with lung cancer, and additional data indicate that decreases in hemoglobin in these patients are associated with impaired survival. Multiple clinical studies have demonstrated that treatment of anemia with erythropoietic agents in patients with lung cancer results in a significant increase in hemoglobin, decrease in transfusions, and improvement in quality of life. Ongoing research is evaluating whether erythropoietic therapy can reduce cognitive impairment associated with lung cancer, cytotoxic therapy, and anemia. Despite the known adverse effects of anemia and the established benefits of erythropoietic therapy in anemic patients with lung cancer, more than half of these patients do not receive any anemia treatment. The purpose of this review is to report results of the European Cancer Anaemia Survey that describe the prevalence of anemia in patients with lung cancer, to review the major studies evaluating the clinical outcomes of erythropoietic therapy in patients with lung cancer, to discuss the recent safety concerns regarding the use of erythropoietic agents in patients with cancer treated to high hemoglobin levels, and to describe various novel therapeutic applications of erythropoietic agents in lung cancer.

Authors
Crawford, J; Kosmidis, PA; Hirsch, FR; Langer, CJ
MLA Citation
Crawford, J, Kosmidis, PA, Hirsch, FR, and Langer, CJ. "Targeting anemia in patients with lung cancer." J Thorac Oncol 1.7 (September 2006): 716-725. (Review)
PMID
17409943
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
1
Issue
7
Publish Date
2006
Start Page
716
End Page
725

2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.

PURPOSE: To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). UPDATE METHODOLOGY: The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. RECOMMENDATIONS: The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.

Authors
Smith, TJ; Khatcheressian, J; Lyman, GH; Ozer, H; Armitage, JO; Balducci, L; Bennett, CL; Cantor, SB; Crawford, J; Cross, SJ; Demetri, G; Desch, CE; Pizzo, PA; Schiffer, CA; Schwartzberg, L; Somerfield, MR; Somlo, G; Wade, JC; Wade, JL; Winn, RJ; Wozniak, AJ; Wolff, AC
MLA Citation
Smith, TJ, Khatcheressian, J, Lyman, GH, Ozer, H, Armitage, JO, Balducci, L, Bennett, CL, Cantor, SB, Crawford, J, Cross, SJ, Demetri, G, Desch, CE, Pizzo, PA, Schiffer, CA, Schwartzberg, L, Somerfield, MR, Somlo, G, Wade, JC, Wade, JL, Winn, RJ, Wozniak, AJ, and Wolff, AC. "2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline." J Clin Oncol 24.19 (July 1, 2006): 3187-3205.
PMID
16682719
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
19
Publish Date
2006
Start Page
3187
End Page
3205
DOI
10.1200/JCO.2006.06.4451

Erythropoiesis-stimulating protein support and survival.

Anemia is common in many patients with cancer treated with chemotherapy. One option for managing chemotherapy-induced anemia (CIA) is erythropoiesis-stimulating proteins (ESPs), which are indicated for the treatment of CIA in patients with most types of cancer. They have been shown to be safe and effective in numerous well-documented studies, and their side effects are well known. The rate of thrombotic events with the long-acting ESP darbepoetin alfa (Aranesp) has been consistent in studies conducted before and after its approval. The association of thrombotic events with high hemoglobin levels or rapid increases in its levels in patients with cancer remains controversial. Adjusting the dose of the ESP to maintain and monitor a target hemoglobin level of 11 to 12 g/dL is certainly prudent and may help prevent or minimize these events. Chemotherapy-induced anemia has been associated with shorter survival in patients with cancer, and the relation is likely multifactorial. Data on the treatment of CIA with ESPs have not shown a consistent effect on survival. Two studies in patients with hemoglobin levels above the target level showed that survival was shorter in the patients treated with ESPs. A review of data from other trials found no effect of ESPs on survival, and other trials suggested a positive effect. This article reviews data on survival in patients treated with ESPs and discusses five large randomized controlled trials of darbepoetin alfa that are addressing this issue.

Authors
Crawford, J
MLA Citation
Crawford, J. "Erythropoiesis-stimulating protein support and survival." Oncology (Williston Park) 20.8 Suppl 6 (July 2006): 39-43. (Review)
PMID
16925111
Source
pubmed
Published In
Oncology
Volume
20
Issue
8 Suppl 6
Publish Date
2006
Start Page
39
End Page
43

Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients.

BACKGROUND: Hospitalization for febrile neutropenia (FN) in cancer patients is associated with considerable morbidity, mortality, and cost. The study was undertaken to better define mortality, length of stay (LOS), cost, and risk factors associated with mortality and prolonged hospitalization in cancer patients with FN. METHODS: The longitudinal discharge database derived from 115 US medical centers was used to study all adult cancer patients hospitalized with FN between 1995 and 2000, comprising a total of 41,779 patients. Primary outcomes included mortality, LOS, and cost per episode. RESULTS: Overall, in-hospital mortality was 9.5%. Patients without any major comorbidities had a 2.6% risk of mortality, whereas 1 major comorbidity was associated with a 10.3% and more than 1 major comorbidity with a > or = 21.4% risk of mortality, respectively. Mean (median) length of stay was 11.5 (6) days, and the mean (median) cost was $19,110 ($8,376) per episode of FN. Patients hospitalized for > or = 10 days (35% of all patients) accounted for 78% of overall cost. Independent major risk factors for inpatient mortality included invasive fungal infections, Gram-negative sepsis, pneumonia and other lung disease, cerebrovascular, renal, and liver disease. Main predictors for LOS > or = 10 days included leukemia, invasive fungal infections, other types of infection, and several comorbid conditions. CONCLUSION: Factors associated with increased mortality, LOS, and cost in hospitalized adult cancer patients with FN include patient characteristics, type of malignancy, comorbidities, and infectious complications. These factors may be useful in identifying patients at increased risk of serious medical complications and mortality for more aggressive supportive care measures.

Authors
Kuderer, NM; Dale, DC; Crawford, J; Cosler, LE; Lyman, GH
MLA Citation
Kuderer, NM, Dale, DC, Crawford, J, Cosler, LE, and Lyman, GH. "Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients." Cancer 106.10 (May 15, 2006): 2258-2266.
PMID
16575919
Source
pubmed
Published In
Cancer
Volume
106
Issue
10
Publish Date
2006
Start Page
2258
End Page
2266
DOI
10.1002/cncr.21847

Becoming a supportive cancer therapy generalist.

Authors
Crawford, J
MLA Citation
Crawford, J. "Becoming a supportive cancer therapy generalist." Support Cancer Ther 3.3 (April 1, 2006): 134-.
PMID
18632485
Source
pubmed
Published In
Supportive cancer therapy
Volume
3
Issue
3
Publish Date
2006
Start Page
134
DOI
10.3816/SCT.2006.n.009

Risk assessment and guidelines for first-cycle colony-stimulating factor use in the management of chemotherapy-induced neutropenia.

Neutropenia is the primary dose-limiting toxicity in patients with cancer treated with systemic chemotherapy. The risk of febrile neutropenia (FN) has been estimated on the basis of the chemotherapy regimen, but studies are now finding a number of patient-related and disease-related risk factors for FN and other complications, such as hospitalization, chemotherapy dose reductions and delays, and mortality. These patient-related risk factors have been incorporated into clinical guidelines for managing neutropenia. The newly released guidelines on the use of myeloid growth factors with cancer chemotherapy of the National Comprehensive Cancer Network use disease- and patient-related factors along with the chemotherapy regimen risk. These guidelines also differ from previous guidelines in that they recommend the routine use of colony-stimulating factors (CSFs) in patients in whom the risk of neutropenia is > 20% (the previous threshold was > or = 40%); this recommendation is based on recent data that show the clinical benefits of filgrastim (Neupogen) and pegfilgrastim (Neulasta) in studies in which the overall populations had FN risks of between 20% and 40%. The use of guidelines such as these in clinical practice will make it possible to target CSFs to appropriate patients in the first cycle of chemotherapy, when the risk of neutropenia is highest.

Authors
Crawford, J
MLA Citation
Crawford, J. "Risk assessment and guidelines for first-cycle colony-stimulating factor use in the management of chemotherapy-induced neutropenia." Oncology (Williston Park) 20.5 Suppl 4 (April 2006): 22-28. (Review)
PMID
16736985
Source
pubmed
Published In
Oncology
Volume
20
Issue
5 Suppl 4
Publish Date
2006
Start Page
22
End Page
28

Colony-stimulating factor use in the context of refined risk and benefit assessments.

Authors
Crawford, J
MLA Citation
Crawford, J. "Colony-stimulating factor use in the context of refined risk and benefit assessments." Oncology (Williston Park) 20.5 Suppl 4 (April 2006): 9-10.
PMID
16736982
Source
pubmed
Published In
Oncology
Volume
20
Issue
5 Suppl 4
Publish Date
2006
Start Page
9
End Page
10

Myelotoxicity from chemotherapy.

Myelosuppression continues to be a major dose-limiting toxicity for most chemotherapy regimens. While the development of growth factors has changed the approach to myelosuppression, costs remain high and can be measured both in terms of quality of life (QOL) and economic outcomes. Growing data suggest that there may also be effects on response and survival in some tumors. This review will highlight the incidence, effect, and treatment/prevention of myelosuppression and briefly discuss the questions that remain.

Authors
Daniel, D; Crawford, J
MLA Citation
Daniel, D, and Crawford, J. "Myelotoxicity from chemotherapy." Semin Oncol 33.1 (February 2006): 74-85. (Review)
PMID
16473646
Source
pubmed
Published In
Seminars in Oncology
Volume
33
Issue
1
Publish Date
2006
Start Page
74
End Page
85
DOI
10.1053/j.seminoncol.2005.11.003

Integrating support into cancer therapy.

Authors
Crawford, J
MLA Citation
Crawford, J. "Integrating support into cancer therapy." Support Cancer Ther 3.2 (January 1, 2006): 71-72.
PMID
18632441
Source
pubmed
Published In
Supportive cancer therapy
Volume
3
Issue
2
Publish Date
2006
Start Page
71
End Page
72
DOI
10.3816/SCT.2006.n.001

A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer.

OBJECTIVE: To determine the feasibility and maximum tolerated dose of dose-dense topotecan as induction chemotherapy before standard therapy (carboplatin plus etoposide alone or in combination with radiotherapy) in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with SCLC and good performance status were eligible. Three 2-week cycles of dose-dense topotecan administered on days 1-3 with granulocyte colony-stimulating factor support were followed by four cycles of standard carboplatin plus etoposide therapy alone (extensive-stage SCLC) or with radiotherapy (limited-stage SCLC). The dose of topotecan was escalated from 1.5 mg/m2/day to 2.5 mg/m2/day in increments of 0.25 mg/m2/day within cohorts of 3-5 patients each. Dose-limiting toxicity was defined as any grade 3 or 4 toxicity resulting in a treatment reduction or a delay of >3 days. RESULTS: Twenty-two patients with SCLC (5 limited-stage, 17 extensive-stage) were enrolled. Treatment was well tolerated. The dose-limiting toxicities were thrombocytopenia and neutropenia, and the maximum tolerated dose of dose-dense topotecan induction therapy was 2.25 mg/m2/day. Overall, topotecan-related grade 3/4 haematological toxicities included neutropenia (n = 4), thrombocytopenia (n = 3) and febrile neutropenia (n = 1). No grade 4 non-haematological toxicities occurred. Grade 3 adverse events included nausea (n = 2), renal toxicity (n = 1) and anorexia (n = 1). Toxicity during the carboplatin plus etoposide +/- radiotherapy phase of therapy was consistent with that reported in previous trials. The overall response rate was 80% for limited-stage and 76% for extensive-stage SCLC. Median survival was 8 months in patients with limited-stage SCLC and 13.5 months for patients with extensive-stage SCLC. CONCLUSION: The results of this phase I study suggest that a regimen of sequential dose-dense topotecan and carboplatin plus etoposide is feasible, and the preliminary activity observed in patients with SCLC warrants further investigation at a starting dose of topotecan 2.25 mg/m2/day.

Authors
Garst, J; Herndon, JE; Shafman, T; Campagna, L; Blackwell, S; Padilla, K; Bjurstrom, T; Andrews, C; Maravich-May, D; Anderson, E; Crawford, J
MLA Citation
Garst, J, Herndon, JE, Shafman, T, Campagna, L, Blackwell, S, Padilla, K, Bjurstrom, T, Andrews, C, Maravich-May, D, Anderson, E, and Crawford, J. "A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer." Clin Drug Investig 26.5 (2006): 257-266.
PMID
17163259
Source
pubmed
Published In
Clinical drug investigation
Volume
26
Issue
5
Publish Date
2006
Start Page
257
End Page
266

Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer

Purpose: To evaluate the efficacy and toxicity of bortezomib ± docetaxel as second-line therapy in patients with relapsed or refractory advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients were randomly assigned to bortezomib 1.5 mg/m2 (arm A) or bortezomib 1.3 mg/m2 plus docetaxel 75 mg/m2 (arm B). A treatment cycle of 21 days comprised four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, docetaxel on day 1. Patients could receive unlimited cycles. The primary end point was response rate. Results: A total of 155 patients were treated, 75 in arm A and 80 in arm B. Baseline characteristics were comparable. Investigator-assessed response rates were 8% in arm A and 9% in arm B. Disease control rates were 29% in arm A and 54% in arm B. Median time to progression was 1.5 months in arm A and 4.0 months in arm B. One-year survival was 39% and 33%, and median survival was 7.4 and 7.8 months in arms A and B, respectively. Adverse effect profiles were as expected in both arms, with no significant additivity. The most common grade ≥ 3 adverse events were neutropenia, fatigue, and dyspnea (4% and 53%, 19% and 26%, and 17% and 14% of patients in arms A and B, respectively). Conclusion: Bortezomib has modest single-agent activity in patients with relapsed or refractory advanced NSCLC using this schedule, with minor enhancement in combination with docetaxel. Additional investigation of bortezomib in NSCLC is warranted in combination with other drugs known to be active, or using different schedules.

Authors
Fanucchi, MP; Fossella, FV; Belt, R; Natale, R; Fidias, P; Carbone, DP; Govindan, R; Raez, LE; Robert, F; Ribeiro, M; Akerley, W; Kelly, K; Limentani, SA; Crawford, J; Reimers, H-J; Axelrod, R; Kashala, O; Sheng, S; Schiller, JH
MLA Citation
Fanucchi, MP, Fossella, FV, Belt, R, Natale, R, Fidias, P, Carbone, DP, Govindan, R, Raez, LE, Robert, F, Ribeiro, M, Akerley, W, Kelly, K, Limentani, SA, Crawford, J, Reimers, H-J, Axelrod, R, Kashala, O, Sheng, S, and Schiller, JH. "Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer." Journal of Clinical Oncology 24.31 (2006): 5025-5033.
PMID
17075122
Source
scival
Published In
Journal of Clinical Oncology
Volume
24
Issue
31
Publish Date
2006
Start Page
5025
End Page
5033
DOI
10.1200/JCO.2006.06.1853

Small cell lung cancer: Clinical Practice Guidelines in Oncology™

In 2005, approximately 26,000 new cases of small cell lung cancer were diagnosed in the United States. When compared with non-small cell lung cancer, SCLC generally has a more rapid doubling time, a higher growth fraction, and earlier development of widespread metastases. SCLC is highly sensitive to initial chemotherapy and radiotherapy. Treatment with chemotherapy plus chest radiotherapy can be curative for some patients with limited-stage SCLC, whereas most patients with extensive-stage disease who undergo chemotherapy alone experience palliated symptoms and prolonged survival. The updated 2006 NCCN guidelines include new principles of surgical resection as well as chemotherapy and radiation dosage changes. © Journal of the National Comprehensive Cancer Network.

Authors
Johnson, BE; Crawford, J; Downey, RJ; Ettinger, DS; Fossella, F; Grecula, JC; Jahan, T; Kalemkerian, GP; Kessinger, A; Koczywas, M; Langer, CJ; Martins, R; Marymont, MH; Niell, HB; Ramnath, N; Robert, F; Jr, CCW
MLA Citation
Johnson, BE, Crawford, J, Downey, RJ, Ettinger, DS, Fossella, F, Grecula, JC, Jahan, T, Kalemkerian, GP, Kessinger, A, Koczywas, M, Langer, CJ, Martins, R, Marymont, MH, Niell, HB, Ramnath, N, Robert, F, and Jr, CCW. "Small cell lung cancer: Clinical Practice Guidelines in Oncology™." JNCCN Journal of the National Comprehensive Cancer Network 4.6 (2006): 602-622.
PMID
16813728
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
4
Issue
6
Publish Date
2006
Start Page
602
End Page
622

The role of Plerixafor (AMD3100) in mobilizing hematopoietic progenitor cells in patients with hematologic malignancies

Authors
Reddy, GK; Crawford, J; Jain, VK
MLA Citation
Reddy, GK, Crawford, J, and Jain, VK. "The role of Plerixafor (AMD3100) in mobilizing hematopoietic progenitor cells in patients with hematologic malignancies." Supportive Cancer Therapy 3.2 (2006): 73-76.
Source
scival
Published In
Supportive cancer therapy
Volume
3
Issue
2
Publish Date
2006
Start Page
73
End Page
76

Topotecan in the treatment of elderly patients with relapsed small-cell lung cancer.

BACKGROUND: Almost 70% of all patients with lung cancer in the United States are>65 years of age, and the incidence of small-cell lung cancer (SCLC) increases with age until the eighth decade of life. However, elderly patients are underrepresented in clinical trials and are often suboptimally treated. The validity of age as a prognostic factor for toxicity or survival remains controversial. PATIENTS AND METHODS: To investigate the safety and efficacy of topotecan (an approved treatment for relapsed SCLC) in older patients, we performed a retrospective analysis in patients >or= 65 years of age versus patients < 65 years of age from 5 large topotecan trials. In all 5 trials, patients received topotecan 1.5 mg/m2 per day via a 30-minute intravenous infusion on days 1 through 5 of a 21-day cycle. Efficacy and tolerability outcomes were assessed for both age groups. RESULTS: Topotecan was similarly tolerated in both age groups, with generally manageable hematologic toxicity. The incidence, duration, and onset of severe hematologic toxicities did not vary significantly with age. In the<65 age group, grade 4 neutropenia and leukopenia were reported in 72% and 32% of patients, respectively; in the >or= 65 age group, grade 4 neutropenia and leukopenia were reported in 77% and 31% of patients, respectively. Grade 4 thrombocytopenia was less common in the<65 age group. Nonhematologic toxicities, median time to progression, and overall survival were comparable between groups. CONCLUSION: This is the first demonstration of the safety and efficacy of topotecan in older patients with recurrent SCLC. Future studies are needed to fully characterize the role of topotecan in the treatment of older patients.

Authors
Garst, J; Buller, R; Lane, S; Crawford, J
MLA Citation
Garst, J, Buller, R, Lane, S, and Crawford, J. "Topotecan in the treatment of elderly patients with relapsed small-cell lung cancer." Clin Lung Cancer 7.3 (November 2005): 190-196.
PMID
16354314
Source
pubmed
Published In
Clinical lung cancer
Volume
7
Issue
3
Publish Date
2005
Start Page
190
End Page
196
DOI
10.3816/CLC.2005.n.035

Shifting guidelines for myeloid growth factors: applications in cancer chemotherapy.

Neutropenia is a frequent dose-limiting complication of chemotherapy. Although myeloid growth factors decrease the risk of febrile neutropenia and the resulting complications of hospitalizations, dose delays, and dose reductions, not all patients need or benefit from the prophylactic administration of myeloid growth factors. A recent risk model showed that the predictors of febrile neutropenia include anthracycline use, poor performance status, and low pretreatment blood counts. These predictors may be used in addition to the intensity of the chosen chemotherapy regimen to determine whether a patient warrants primary prophylaxis with myeloid growth factors. The 2005 guidelines of the National Comprehensive Cancer Network call for primary prophylactic use in all patients with a risk of febrile neutropenia above 20%. Other recent studies show that pegylated filgrastim is also effective at preventing febrile neutropenia in patients receiving intermediate- risk chemotherapy.

Authors
Daniel, DB; Crawford, J; National Comprehensive Cancer Network,
MLA Citation
Daniel, DB, Crawford, J, and National Comprehensive Cancer Network, . "Shifting guidelines for myeloid growth factors: applications in cancer chemotherapy." Curr Hematol Rep 4.6 (November 2005): 441-445. (Review)
PMID
16232380
Source
pubmed
Published In
Current hematology reports
Volume
4
Issue
6
Publish Date
2005
Start Page
441
End Page
445

Criterion validity of Medicare chemotherapy claims in Cancer and Leukemia Group B breast and lung cancer trial participants.

To determine the accuracy with which Medicare claims data measure chemotherapy use in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We compared gold-standard clinical trial data for 175 elderly cancer patients treated in two Cancer and Leukemia Group B (CALGB) breast and lung cancer trials (i.e., 45 from trial 9344 and 130 from trial 9730) with contemporaneous ambulatory and in-patient Medicare health insurance claims data from Centers for Medicare and Medicaid Services (CMS). The breast trial participants studied were those elderly enrolled between 1995 and 1997 and treated with doxorubicin and cyclophosphamide or this combination with paclitaxel. The lung trial participants studied were those elderly enrolled between 1998 and 2000 and treated with paclitaxel and carboplatin or paclitaxel alone. Comparing CALGB data with Medicare claims, we found the crude sensitivity for chemotherapy administration was 93% (95% confidence interval [CI] = 88% to 96%). Individual chemotherapy agents had similarly high sensitivities, ranging from 81% (95% CI = 70% to 89%) for carboplatin to 91% (95% CI = 79% to 98%) for cyclophosphamide. Agent-specific specificities were 100%. CMS data reliably captured repeat administration of chemotherapy to within one cycle. Administrative Medicare claims data appear to be a valid source of information for chemotherapy administered to elderly Medicare beneficiaries with cancer.

Authors
Lamont, EB; Herndon, JE; Weeks, JC; Henderson, IC; Lilenbaum, R; Schilsky, RL; Christakis, NA
MLA Citation
Lamont, EB, Herndon, JE, Weeks, JC, Henderson, IC, Lilenbaum, R, Schilsky, RL, and Christakis, NA. "Criterion validity of Medicare chemotherapy claims in Cancer and Leukemia Group B breast and lung cancer trial participants." J Natl Cancer Inst 97.14 (July 20, 2005): 1080-1083.
PMID
16030306
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
97
Issue
14
Publish Date
2005
Start Page
1080
End Page
1083
DOI
10.1093/jnci/dji189

Myeloid growth factors clinical practice guidelines in oncology.

Authors
Crawford, J; Althaus, B; Armitage, J; Blayney, DW; Cataland, S; Dale, DC; Demetri, GD; Foran, J; Heaney, ML; Htoy, S; Kloth, DD; Lyman, GH; Michaud, L; Motl, S; Vadhan-Raj, S; Wong, MK; National Comprehensive Cancer Network,
MLA Citation
Crawford, J, Althaus, B, Armitage, J, Blayney, DW, Cataland, S, Dale, DC, Demetri, GD, Foran, J, Heaney, ML, Htoy, S, Kloth, DD, Lyman, GH, Michaud, L, Motl, S, Vadhan-Raj, S, Wong, MK, and National Comprehensive Cancer Network, . "Myeloid growth factors clinical practice guidelines in oncology." J Natl Compr Canc Netw 3.4 (July 2005): 540-555.
PMID
16038645
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
3
Issue
4
Publish Date
2005
Start Page
540
End Page
555

Bronchial stenosis: an underreported complication of high-dose external beam radiotherapy for lung cancer?

PURPOSE: To assess the incidence of clinically significant bronchial stenosis in patients treated with high doses (i.e., >70 Gy) of twice-daily external beam radiation therapy (RT). METHODS AND MATERIALS: The outcomes of 103 patients with unresectable non-small-cell lung cancer, treated twice daily to doses ranging from 7080 to 8640 cGy between 1992 and 2001, were analyzed. Most were treated on prospective clinical trials. For the dose-effect comparison, the patients were divided on the basis of the total dose: 67 received 74 Gy (range, 70.8-74.5 Gy; median, 73.6 Gy), 20 received 80 Gy, and 16 received 86 Gy (range, 85.2-86.4 Gy; median, 86.4 Gy). Sixty-six patients received sequential chemotherapy before RT. RT-induced bronchial stenosis was defined as symptomatic airway narrowing diagnosed by bronchoscopy or computed tomography scan without evidence of recurrent tumor in that region. RESULTS: Eight patients developed RT-induced, clinically significant, bronchial stenosis 2-48 months (median, 6 months) after RT. The 1-year and 4-year actuarial rate of stenosis was 7% and 38%, respectively. The median overall survival was 2.5 years (5 of 8 were alive at the writing of this report). A suggestion was also found of a dose-response effect with external beam radiotherapy-induced stenosis, with a rate of 4% and 25% at a dose of approximately 74 Gy and 86 Gy, respectively. CONCLUSION: Radiation therapy-induced bronchial stenosis is a significant clinical complication of dose escalation for lung cancer. This complication has been previously mentioned in the literature, but ours is the largest report to date, and the findings suggest that the risk rises with increasing dose. It is likely that this process would manifest in more patients if their disease were controlled well enough for more prolonged survival.

Authors
Miller, KL; Shafman, TD; Anscher, MS; Zhou, S-M; Clough, RW; Garst, JL; Crawford, J; Rosenman, J; Socinski, MA; Blackstock, W; Sibley, GS; Marks, LB
MLA Citation
Miller, KL, Shafman, TD, Anscher, MS, Zhou, S-M, Clough, RW, Garst, JL, Crawford, J, Rosenman, J, Socinski, MA, Blackstock, W, Sibley, GS, and Marks, LB. "Bronchial stenosis: an underreported complication of high-dose external beam radiotherapy for lung cancer?." Int J Radiat Oncol Biol Phys 61.1 (January 1, 2005): 64-69.
PMID
15629595
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
61
Issue
1
Publish Date
2005
Start Page
64
End Page
69
DOI
10.1016/j.ijrobp.2004.02.066

Effect of outpatient treatment of febrile neutropenia on the risk threshold for the use of CSF in patients with cancer treated with chemotherapy.

OBJECTIVES: Febrile neutropenia (FN) in patients with cancer treated with chemotherapy has traditionally been managed with inpatient broad-spectrum antibiotics until the infection and neutropenia have resolved. A newer strategy is outpatient oral or intravenous antibiotics in selected patients after an initial hospitalization. We sought to determine these costs, both overall and relative to those of traditional management, and the optimal role of prophylactic colony-stimulating factor (CSF) in patients at greatest risk for FN. METHODS: Existing economic decision models were modified by incorporating a treatment strategy for FN in which patients are classified as high- and low-risk according to criteria described by Talcott. Low-risk patients were assumed to be treated as outpatients. Overall costs with the revised economic model were assessed and sensitivity analyses were performed. RESULTS: The costs of an episode of FN were estimated as 1) no CSF: dollar 13,355; 2) CSF with hospitalization for FN: dollar 8677; and 3) CSF with risk stratification and outpatient management in low-risk patients: dollar 8188. The risk threshold for the cost-effective use of CSF was only slightly lower with outpatient treatment. When all patients with FN are treated as inpatients and the cost of hospitalization is dollar 1750/day the risk threshold for FN at which prophylactic CSF becomes cost-effective is 16%. It is 15% when low-risk patients are treated as outpatients. CONCLUSIONS: Outpatient treatment slightly decreases the risk threshold for FN at which prophylactic CSF becomes cost-effective. The limited economic effect of this strategy may be because the patients who were at greatest risk of complications had significantly longer lengths of stay and accounted for most of the hospitalization costs.

Authors
Cosler, LE; Sivasubramaniam, V; Agboola, O; Crawford, J; Dale, D; Lyman, GH
MLA Citation
Cosler, LE, Sivasubramaniam, V, Agboola, O, Crawford, J, Dale, D, and Lyman, GH. "Effect of outpatient treatment of febrile neutropenia on the risk threshold for the use of CSF in patients with cancer treated with chemotherapy." Value Health 8.1 (January 2005): 47-52.
PMID
15841893
Source
pubmed
Published In
Value in Health
Volume
8
Issue
1
Publish Date
2005
Start Page
47
End Page
52
DOI
10.1111/j.1524-4733.2005.03099.x

Predictors of chemotherapy-induced neutropenia and its complications: Results from a prospective nationwide registry

Authors
Wolff, D; Culakova, E; Poniewierski, MS; Lyman, GH; Dale, DC; Crawford, J
MLA Citation
Wolff, D, Culakova, E, Poniewierski, MS, Lyman, GH, Dale, DC, and Crawford, J. "Predictors of chemotherapy-induced neutropenia and its complications: Results from a prospective nationwide registry." Journal of Supportive Oncology 3.6 SUPPL. 4 (2005): 24-25.
Source
scival
Published In
Journal of Supportive Oncology
Volume
3
Issue
6 SUPPL. 4
Publish Date
2005
Start Page
24
End Page
25

Consensus on medical treatment of non-small-cell lung cancer - Update 2004

Authors
Zielinski, CC; Krainer, M; Pirker, R; Tomek, S; Zöchbauer-Müller, S; Beinert, T; Crawford, J; Fischer, JR; Georgoulias, V; Gridelli, C; Hirsch, F; Jassem, J; Herold, C; Kosmidis, P; Krzakowski, M; Manegold, C; Pujol, JL; Thatcher, N; Zandwijk, NV; Zwitter, M
MLA Citation
Zielinski, CC, Krainer, M, Pirker, R, Tomek, S, Zöchbauer-Müller, S, Beinert, T, Crawford, J, Fischer, JR, Georgoulias, V, Gridelli, C, Hirsch, F, Jassem, J, Herold, C, Kosmidis, P, Krzakowski, M, Manegold, C, Pujol, JL, Thatcher, N, Zandwijk, NV, and Zwitter, M. "Consensus on medical treatment of non-small-cell lung cancer - Update 2004." Lung Cancer 50.1 (2005): 129-137.
Source
scival
Published In
Lung Cancer
Volume
50
Issue
1
Publish Date
2005
Start Page
129
End Page
137
DOI
10.1016/j.lungcan.2005.05.014

Concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer.

Over the last two decades, several approaches to multimodality therapy have been investigated in patients with advanced unresectable non-small cell lung cancer. These include induction chemotherapy and concurrent chemoradiotherapy. Both approaches have been shown to be superior to radiation therapy alone. However, in several randomized trials, concomitant chemoradiotherapy was shown to be superior to the induction chemotherapy approach. It has been hypothesized that the addition of systemic dose sequential chemotherapy to concurrent chemoradiotherapy, either as induction or as consolidation chemotherapy, might further improve survival rates. Recently, the Cancer and Leukemia Group B reported on a randomized phase III trial directly evaluating the addition of two cycles of carboplatin and paclitaxel to concurrent chemoradiotherapy. In this study, induction chemotherapy failed to further improve survival rates of concurrent chemoradiotherapy. A previously conducted randomized phase II study also suggested no benefit from the addition of induction chemotherapy to concomitant chemoradiotherapy. Favorable phase II data have been published supporting the use of consolidation chemotherapy. However, to date, no large randomized study evaluating a possible benefit from consolidation chemotherapy has been completed. In addition to evaluating optimal sequencing strategies of combined modality therapy, current investigations are also focusing on the integration of novel agents, including chemotherapeutic and targeted therapies. Currently ongoing trials involving novel approaches are reviewed here.

Authors
Vokes, EE; Crawford, J; Bogart, J; Socinski, MA; Clamon, G; Green, MR
MLA Citation
Vokes, EE, Crawford, J, Bogart, J, Socinski, MA, Clamon, G, and Green, MR. "Concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 11.13 Pt 2 (2005): 5045s-5050s.
PMID
16000612
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
13 Pt 2
Publish Date
2005
Start Page
5045s
End Page
5050s

Limited-stage small-cell lung cancer (stages I-III): Observations from the National Cancer Data Base

The standard treatment of limited-stage small-cell lung cancer (LS-SCLC) has changed over the past 15 years. Standard treatment for LS-SCLC currently involves multiple-agent chemotherapy and early concurrent thoracic radiation therapy. Four patient cohorts (total number of patients, 22,969) diagnosed with LS-SCLC in 1985 (N = 2123), 1990 (N = 6279), 1995 (N = 7815), and 2000 (N = 6752) were studied in order to describe demographic and treatment pattern changes as well as 5-year survival rates across cohorts. Women composed 40.2% of patients in the 1985 cohort but represented a significant proportional increase over each successive cohort, representing 50.8% of the 2000 cohort. The proportion of patients aged ≥ 70 years also significantly increased over time, from 31.6% in 1985 to 44.9% in 2000 (P < 0.001). Over these years, the use of chemoradiation as the primary treatment for patients with LS-SCLC increased from 34.6% to 51.9% (from 37% to 60.5% for patients aged < 70 years, and from 29.5% to 41.3% for patients aged ≥ 70 years). During the same time, the use of chemotherapy as the sole treatment decreased from 30.7% in 1985 to 21.7% in 2000. Chemotherapy as the sole treatment was used in 25.9% of the population ≥ 70 years of age in 2000, compared with 18.3% in patients aged < 70 years. The percent of patients for which there was no treatment given did not change significantly between the cohorts (14.3% in 1985 and 13.7% in 2000; P < 0.001). The 5-year survival rates and 95% confidence intervals (CIs) for the 1985, 1990, and 1995 cohorts of all ages of patients treated with chemoradiation therapy are as follows: 10.5% (CI, 6.75%-14.25%), 11.88% (CI, 9.63%-14.13%), and 13.3% (CI, 11.2%-15.4%). Between 1985 and 2000 there was a significant increase in the percentage of women diagnosed with LS-SCLC. The use of combined chemotherapy and radiation therapy also increased during this period. This increase in chemoradiation therapy was associated with a decreased use of chemotherapy alone. Despite changes in demographics and treatment during these time intervals, the 5-year survival for patients with LS-SCLC treated with chemoradiation therapy did not increase significantly. These results demonstrate the continued need for the evaluation of new treatments in this group of patients.

Authors
Gaspar, LE; Gay, EG; Crawford, J; Putnam, JB; Herbst, RS; Bonner, JA
MLA Citation
Gaspar, LE, Gay, EG, Crawford, J, Putnam, JB, Herbst, RS, and Bonner, JA. "Limited-stage small-cell lung cancer (stages I-III): Observations from the National Cancer Data Base." Clinical Lung Cancer 6.6 (2005): 355-360.
PMID
15943896
Source
scival
Published In
Clinical lung cancer
Volume
6
Issue
6
Publish Date
2005
Start Page
355
End Page
360

Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR. 18

Purpose: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. Patients and Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. Results: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). Conclusion: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC. © 2005 by American Society of Clinical Oncology.

Authors
Leighl, NB; Paz-Ares, L; Douillard, J-Y; Peschel, C; Arnold, A; Depierre, A; Santoro, A; Betticher, DC; Gatzemeier, U; Jassem, J; Crawford, J; Tu, D; Bezjak, A; Humphrey, JS; Voi, M; Galbraith, S; Hann, K; Seymour, L; Shepherd, FA
MLA Citation
Leighl, NB, Paz-Ares, L, Douillard, J-Y, Peschel, C, Arnold, A, Depierre, A, Santoro, A, Betticher, DC, Gatzemeier, U, Jassem, J, Crawford, J, Tu, D, Bezjak, A, Humphrey, JS, Voi, M, Galbraith, S, Hann, K, Seymour, L, and Shepherd, FA. "Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR. 18." Journal of Clinical Oncology 23.12 (2005): 2831-2839.
PMID
15837997
Source
scival
Published In
Journal of Clinical Oncology
Volume
23
Issue
12
Publish Date
2005
Start Page
2831
End Page
2839
DOI
10.1200/JCO.2005.04.044

First-cycle risk of severe and febrile neutropenia in cancer patients receiving systemic chemotherapy: Results from a prospective nationwide study

Authors
Crawford, J; Wolff, D; Culakova, E; Poniewierski, MS; Selby, C; Dale, D; Lyman, GH
MLA Citation
Crawford, J, Wolff, D, Culakova, E, Poniewierski, MS, Selby, C, Dale, D, and Lyman, GH. "First-cycle risk of severe and febrile neutropenia in cancer patients receiving systemic chemotherapy: Results from a prospective nationwide study." Journal of Supportive Oncology 3.2 SUPPL. 1 (2005): 52-53.
Source
scival
Published In
Journal of Supportive Oncology
Volume
3
Issue
2 SUPPL. 1
Publish Date
2005
Start Page
52
End Page
53

Risk of neutropenic complications based on a prospective nationwide registry of cancer patients initiating systemic chemotherapy

Authors
Wolff, DA; Crawford, J; Dale, DC; Poniewierski, MS; Lyman, GH
MLA Citation
Wolff, DA, Crawford, J, Dale, DC, Poniewierski, MS, and Lyman, GH. "Risk of neutropenic complications based on a prospective nationwide registry of cancer patients initiating systemic chemotherapy." Journal of Supportive Oncology 3.2 SUPPL. 1 (2005): 56-57.
Source
scival
Published In
Journal of Supportive Oncology
Volume
3
Issue
2 SUPPL. 1
Publish Date
2005
Start Page
56
End Page
57

The importance of chemotherapy dose intensity in lung cancer.

The evidence for the importance of maintaining full dose on schedule chemotherapy for lung cancer varies considerably by histologic type. Several studies have evaluated chemotherapy dose and dose intensity in small cell lung cancer; fewer studies have evaluated the importance of chemotherapy in non-small cell lung cancer. The current guidelines of the National Comprehensive Cancer Network recommend adjuvant chemotherapy in most patients with resectable disease, and there is increasing evidence that chemotherapy benefits elderly patients as much as younger patients. Clinical trials in the setting of palliative treatment of advanced non-small cell lung cancer have focused on testing new regimens rather than evaluating the impact of maintaining the dose and schedule of standard chemotherapy regimens. However, in light of the potential curative role of chemotherapy in the adjuvant setting, the optimal doses and schedules of these regimens may have an important impact on outcomes. In addition, data suggest that responses in the neoadjuvant setting correlate with survival, and this may also be an appropriate setting in which to test the effect of the chemotherapy dose and schedule. Survival is the primary measure of treatment efficacy, but other end points, such as quality of life and disease stability, should also be considered in advanced disease. Because new regimens will shape the choice of treatment in the adjuvant and neoadjuvant settings, it is important to determine the significance of maintaining full dose on schedule with conventional chemotherapy regimens to ensure optimal outcomes in the treatment of lung cancer.

Authors
Crawford, J
MLA Citation
Crawford, J. "The importance of chemotherapy dose intensity in lung cancer." Semin Oncol 31.6 Suppl 15 (December 2004): 25-31. (Review)
PMID
15726536
Source
pubmed
Published In
Seminars in Oncology
Volume
31
Issue
6 Suppl 15
Publish Date
2004
Start Page
25
End Page
31
DOI
10.1053/j.seminoncol.2004.11.025

Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin's lymphoma: a nationwide study.

PURPOSE: To assess the incidence of and risk factors for reduced relative dose-intensity (RDI) in patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL). METHODS: A nationwide survey was conducted of 567 oncology practices with data extracted from the records of 4,522 patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); CHOP-rituximab (CHOP-R); or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). The primary outcome was the average RDI for each regimen based on both planned and reference standards. Other assessments included the incidence of febrile neutropenia and patterns of colony-stimulating factor (CSF) use, as well as the average RDI in high-risk subgroups. RESULTS: Dose reductions > or = 15% occurred in 40% of patients and treatment delays > or = 7 days occurred in 24% of patients, resulting in 53% and 48% of patients receiving an RDI less than 85% of the minimum six-cycle and National Comprehensive Cancer Network guideline standards, respectively. Reduced RDI was more prevalent in older patients, with 60% of patients older than 60 years receiving RDI less than 85%. Multivariate analysis identified several independent predictors for reduced RDI, including age older than 60 years, advanced disease stage, poor performance status, and no prophylactic CSF use. Age was no longer a significant risk factor in patients who received prophylactic CSF. CONCLUSION: Patients with aggressive and potentially curable NHL treated with CHOP, CHOP-R, or CNOP frequently receive reduced RDI. Predictive models based on the risk factors identified for reduced RDI should enable the targeted use of appropriate supportive care, facilitating the delivery of full chemotherapy doses on schedule.

Authors
Lyman, GH; Dale, DC; Friedberg, J; Crawford, J; Fisher, RI
MLA Citation
Lyman, GH, Dale, DC, Friedberg, J, Crawford, J, and Fisher, RI. "Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin's lymphoma: a nationwide study." J Clin Oncol 22.21 (November 1, 2004): 4302-4311.
PMID
15381684
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
21
Publish Date
2004
Start Page
4302
End Page
4311
DOI
10.1200/JCO.2004.03.213

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

PURPOSE: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). METHODS: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. RESULTS: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately 80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. CONCLUSION: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.

Authors
Marks, LB; Garst, J; Socinski, MA; Sibley, G; Blackstock, AW; Herndon, JE; Zhou, S; Shafman, T; Tisch, A; Clough, R; Yu, X; Turrisi, A; Anscher, M; Crawford, J; Rosenman, J; Carolina Conformal Therapy Consortium,
MLA Citation
Marks, LB, Garst, J, Socinski, MA, Sibley, G, Blackstock, AW, Herndon, JE, Zhou, S, Shafman, T, Tisch, A, Clough, R, Yu, X, Turrisi, A, Anscher, M, Crawford, J, Rosenman, J, and Carolina Conformal Therapy Consortium, . "Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium." J Clin Oncol 22.21 (November 1, 2004): 4329-4340.
PMID
15514374
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
21
Publish Date
2004
Start Page
4329
End Page
4340
DOI
10.1200/JCO.2004.02.165

Combined modality trials of the Cancer and Leukemia Group B in stage III non-small-cell lung cancer: analysis of factors influencing survival and toxicity.

BACKGROUND: Combined modality therapy (CMT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC); however, insufficient data are available regarding prognostic factors in this disease setting. PATIENTS AND METHODS: Six hundred and ninety-four patients included in five trials conducted by the Cancer and Leukemia Group B evaluating CMT in stage III NSCLC were included in this analysis. The primary objective was to identify factors that were predictors of survival and selected radiation-related toxicities using Cox regression models and logistic regression analysis. RESULTS: The Cox model shows that performance status (PS) 1 [hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.06-1.45; P=0.009] and thoracic radiation therapy (TRT) only (HR 1.58; 95% CI 1.22-2.05; P=0.001) predicted for poorer survival, while baseline hemoglobin >/=12 g/dl predicted for improved survival (HR 0.67; 95% CI 0.55-0.81; P 5% weight loss (OR 2.9; 95% CI 1.3-6.6; P=0.008) and patients receiving concurrent chemoradiation (OR 7.3; 95% CI 3.4-15.6; P=0.0001). CONCLUSIONS: Baseline hemoglobin and PS, as well as the use of CMT, have the greatest effect on survival in unresectable stage III NSCLC. The use of concurrent chemoradiation increases the risk of esophagitis, which remains the primary radiation-related toxicity.

Authors
Socinski, MA; Zhang, C; Herndon, JE; Dillman, RO; Clamon, G; Vokes, E; Akerley, W; Crawford, J; Perry, MC; Seagren, SL; Green, MR
MLA Citation
Socinski, MA, Zhang, C, Herndon, JE, Dillman, RO, Clamon, G, Vokes, E, Akerley, W, Crawford, J, Perry, MC, Seagren, SL, and Green, MR. "Combined modality trials of the Cancer and Leukemia Group B in stage III non-small-cell lung cancer: analysis of factors influencing survival and toxicity." Ann Oncol 15.7 (July 2004): 1033-1041.
PMID
15205196
Source
pubmed
Published In
Annals of Oncology
Volume
15
Issue
7
Publish Date
2004
Start Page
1033
End Page
1041
DOI
10.1093/annonc/mdh282

Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC.

BACKGROUND: To evaluate the activity and tolerability of gemcitabine plus irinotecan or docetaxel as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients with chemotherapy-naïve stage IIIB or IV NSCLC were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8, plus either irinotecan 100 mg/m2 or docetaxel 40 mg/m2 on days 1 and 8. Treatment was administered every 3 weeks. RESULTS: Of the 80 enrolled patients with stage IIIB or IV NSCLC, 78 were evaluable for activity and safety. Overall response rates, consisting of partial responses, were 12.8% [95% confidence interval (CI) 4% to 35%] for gemcitabine-irinotecan and 23.1% (95% CI 10% to 42%) for gemcitabine-docetaxel. Median overall survival was 7.95 months (95% CI 5.2-10.2) and 12.8 months (95% CI 7.9-17.1) for gemcitabine-irinotecan and gemcitabine-docetaxel, respectively. The corresponding estimated 1-year survivals were 23% and 51%, respectively. The 2-year survival rate in arm A (gemcitabine-irinotecan) is not currently estimable. The 2-year survival rate for arm B (gemcitabine-docetaxel) is 22% (95% CI 6% to 37%). Both combinations were well tolerated; the most common hematological toxicity was neutropenia, which occurred in 26% of patients in each treatment arm. CONCLUSIONS: These results suggest that gemcitabine plus docetaxel or irinotecan is well tolerated in patients with chemotherapy-naïve advanced NSCLC. The survival data with the combination gemcitabine-docetaxel are promising. Gemcitabine-docetaxel combination therapy may be particularly useful for patients who have experienced toxicities with a platinum regimen or in patients who may be more susceptible to platinum-related toxicity.

Authors
Rocha Lima, CM; Rizvi, NA; Zhang, C; Herndon, JE; Crawford, J; Govindan, R; King, GW; Green, MR; Cancer Leukemia Group B,
MLA Citation
Rocha Lima, CM, Rizvi, NA, Zhang, C, Herndon, JE, Crawford, J, Govindan, R, King, GW, Green, MR, and Cancer Leukemia Group B, . "Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC." Ann Oncol 15.3 (March 2004): 410-418. (Review)
PMID
14998842
Source
pubmed
Published In
Annals of Oncology
Volume
15
Issue
3
Publish Date
2004
Start Page
410
End Page
418

Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management.

Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes. The authors reviewed the recent literature to provide an update on research in chemotherapy-induced neutropenia and its complications and impact, and they discuss the implications of this work for improving the management of patients with cancer who are treated with myelosuppressive chemotherapy. Despite its importance as the primary dose-limiting toxicity of chemotherapy, much concerning neutropenia and its consequences and impact remains unknown. Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality, and costs. Much research has sought to identify risk factors that may predispose patients to neutropenic complications, including febrile neutropenia, in an effort to predict better which patients are at risk and to use preventive strategies, such as prophylactic colony-stimulating factors, more cost-effectively. Neutropenic complications associated with myelosuppressive chemotherapy are a significant cause of morbidity and mortality, possibly compromised treatment outcomes, and excess healthcare costs. Research in quantifying the risk of neutropenic complications may make it possible in the near future to target patients at greater risk with appropriate preventive strategies, thereby maximizing the benefits and minimizing the costs.

Authors
Crawford, J; Dale, DC; Lyman, GH
MLA Citation
Crawford, J, Dale, DC, and Lyman, GH. "Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management." Cancer 100.2 (January 15, 2004): 228-237. (Review)
PMID
14716755
Source
pubmed
Published In
Cancer
Volume
100
Issue
2
Publish Date
2004
Start Page
228
End Page
237
DOI
10.1002/cncr.11882

Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, with an extracellular ligand-binding domain and intracellular tyrosine kinase domain. Ligand binding induces EGFR dimerization and autophosphorylation on several tyrosine residues in the intracellular domain, leading to mitogenic signal transduction. EGFR overexpression correlates with a poor prognosis and is often associated with malignant transformation in a variety of epithelial cancers. ABX-EGF is a high-affinity (dissociation constant KD = 5 × 10-11 M) fully human IgG2 monoclonal antibody against human EGFR. ABX-EGF binds EGFR and blocks receptor binding of EGF and transforming growth factor-α, inhibiting EGFR tyrosine phosphorylation and tumor cell activation. ABX-EGF prevents tumor formation and eradicates large, established A431 tumors in xenograft models. Tumor growth inhibition occurs at relatively low doses, without concomitant chemotherapy or radiotherapy. When combined with chemotherapeutic agents, ABX-EGF has resulted in additive antitumor activity. A Phase I clinical trial has demonstrated activity in several tumor types, and the results from a Phase II trial for renal cell cancer also showed modest activity. Therapy was generally well tolerated without statistically significant adverse events. Monoclonal antibody blockade of EGFR represents a new and exciting direction in cancer therapy. © 2004 Elsevier Inc.

Authors
Foon, KA; Yang, X-D; Weiner, LM; Belldegrun, AS; Figlin, RA; Crawford, J; Rowinsky, EK; Dutcher, JP; Vogelzang, NJ; Gollub, J; Thompson, JA; Schwartz, G; Bukowski, RM; Roskos, LK; Schwab, GM
MLA Citation
Foon, KA, Yang, X-D, Weiner, LM, Belldegrun, AS, Figlin, RA, Crawford, J, Rowinsky, EK, Dutcher, JP, Vogelzang, NJ, Gollub, J, Thompson, JA, Schwartz, G, Bukowski, RM, Roskos, LK, and Schwab, GM. "Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody." International Journal of Radiation Oncology Biology Physics 58.3 (2004): 984-990.
PMID
14967460
Source
scival
Published In
International Journal of Radiation Oncology Biology Physics
Volume
58
Issue
3
Publish Date
2004
Start Page
984
End Page
990
DOI
10.1016/j.ijrobp.2003.09.098

Erratum: Chemotherapy-induced neutropenia: Risks, consequences, and new directions for its management (Cancer (2004) 100 (228-237))

Authors
Crawford, J; Dale, DC; Lyman, GH
MLA Citation
Crawford, J, Dale, DC, and Lyman, GH. "Erratum: Chemotherapy-induced neutropenia: Risks, consequences, and new directions for its management (Cancer (2004) 100 (228-237))." Cancer 100.9 (2004): 1993-1994.
Source
scival
Published In
Cancer
Volume
100
Issue
9
Publish Date
2004
Start Page
1993
End Page
1994

Improving the management of chemotherapy-induced neutropenia

Authors
Crawford, J
MLA Citation
Crawford, J. "Improving the management of chemotherapy-induced neutropenia." Journal of Supportive Oncology 2.2 SUPPL. (2004): 36-39.
PMID
16108418
Source
scival
Published In
Journal of Supportive Oncology
Volume
2
Issue
2 SUPPL.
Publish Date
2004
Start Page
36
End Page
39

Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices.

PURPOSE: This retrospective study was undertaken to assess practice patterns in adjuvant chemotherapy for early-stage breast cancer (ESBC) and to define the incidence and predictive factors of reduced relative dose-intensity (RDI). PATIENTS AND METHODS: A nationwide survey of 1,243 community oncology practices was conducted, with data extracted from records of 20,799 ESBC patients treated with adjuvant chemotherapy. Assessments included demographic and clinical characteristics, chemotherapy dose modifications, incidence of febrile neutropenia, and patterns of use of colony-stimulating factor (CSF). Dose-intensity was compared with published reference standard regimens. RESULTS: Dose reductions > or =15% occurred in 36.5% of patients, and there were treatment delays > or =7 days in 24.9% of patients, resulting in 55.5% of patients receiving RDI less than 85%. Nearly two thirds of patients received RDI less than 85% when adjusted for differences in regimen dose-intensity. Multivariate analysis identified several independent predictors for reduced RDI, including increased age; chemotherapy with cyclophosphamide, methotrexate, and fluorouracil, or cyclophosphamide, doxorubicin, and fluorouracil; a 28-day schedule; body-surface area greater than 2 m2; and no primary CSF prophylaxis. CSF was often initiated late in the chemotherapy cycle. CONCLUSION: Patients with ESBC are at substantial risk for reduced RDI when treated with adjuvant chemotherapy. Patients at greatest risk include older patients, overweight patients, and those receiving three-drug combinations or 28-day schedules. Predictive models based on such risk factors should enable the selective application of supportive measures in an effort to deliver full dose-intensity chemotherapy.

Authors
Lyman, GH; Dale, DC; Crawford, J
MLA Citation
Lyman, GH, Dale, DC, and Crawford, J. "Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices." J Clin Oncol 21.24 (December 15, 2003): 4524-4531.
PMID
14673039
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
24
Publish Date
2003
Start Page
4524
End Page
4531
DOI
10.1200/JCO.2003.05.002

Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's lymphoma receiving CHOP chemotherapy.

We sought to identify risk factors associated with the time to febrile neutropenia in patients with intermediate-grade, non-Hodgkin's lymphoma (NHL) who were receiving treatment with CHOP chemotherapy. Data were collected from 12 community and academic oncology practices participating in the Oncology Practice Pattern Study between 1991 and 1999. We reviewed the medical records of 577 intermediate-grade NHL patients who received initial CHOP chemotherapy and evaluated risk factors associated with time to first febrile neutropenic event. A febrile neutropenic event was defined as a body temperature of > 100.6 degrees F and an ANC nadir < 1000/mm3. A total of 160 patients experienced 224 febrile neutropenic events. The risk of febrile neutropenia was significantly associated with age > or = 65 years (p = 0.001), cardiovascular disease (p = 0.020), renal disease (p = 0.006), baseline hemoglobin < 12 g/dl (p = 0.018), > 80% planned average relative dose intensity (ARDI; p = 0.018), and no prophylactic colony-stimulating factor (CSF) use (p = 0.046). First febrile neutropenic events occurred by day 14 of cycle 1 in one-half of patients experiencing febrile neutropenia. In multivariate analysis, the risk of febrile neutropenia remained significantly associated with age > or = 65 years (HR = 1.65, 95% CI: 1.18-2.32), renal disease (HR = 1.91. 95% CI: 1.10-3.30), cardiovascular disease (HR = 1.54, 95% CI: 1.02-2.33), baseline hemoglobin < 12 g/dl (HR = 1.44, 95% CI: 1.04-2.00), > 80% planned CHOP ARDI (HR = 2.41, 95% CI: 1.30-4.47), and no CSF prophylaxis (HR = 2.13, 95% CI: 1.20-3.76). Such a model may permit the identification of patients at greatest risk of febrile neutropenia and, therefore, candidates for the selective prophylactic use of the hematopoietic growth factors.

Authors
Lyman, GH; Morrison, VA; Dale, DC; Crawford, J; Delgado, DJ; Fridman, M; OPPS Working Group, ; ANC Study Group,
MLA Citation
Lyman, GH, Morrison, VA, Dale, DC, Crawford, J, Delgado, DJ, Fridman, M, OPPS Working Group, , and ANC Study Group, . "Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's lymphoma receiving CHOP chemotherapy." Leuk Lymphoma 44.12 (December 2003): 2069-2076.
PMID
14959849
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
44
Issue
12
Publish Date
2003
Start Page
2069
End Page
2076

Small-cell lung cancer: a review of clinical trials.

Small-cell lung cancer (SCLC) is expected to account for 25% of the approximate 170,000 cases of lung cancer diagnosed in the United States in 2002. Although sensitive and responsive to chemotherapy, SCLC has an increased propensity for early metastases, with relapses being common and long-term survival rates being poor. Clinical trials have played a vital role in expanding our knowledge base for this disease and have resulted in newer modalities, including chemotherapeutic agents, prophylactic cranial irradiation, and thoracic radiotherapy designed to improve overall outcomes. Clinical trials have also served to clarify the role of surgery in a disease that traditionally has been thought to be nonoperable. This review will focus on the results of clinical trials that have had an effect on the treatments of patients with limited and extensive-stage SCLC, with recommendations from the National Comprehensive Cancer Network being emphasized.

Authors
Riedel, RF; Crawford, J
MLA Citation
Riedel, RF, and Crawford, J. "Small-cell lung cancer: a review of clinical trials." Semin Thorac Cardiovasc Surg 15.4 (October 2003): 448-456. (Review)
PMID
14710387
Source
pubmed
Published In
Seminars in Thoracic and Cardiovascular Surgery
Volume
15
Issue
4
Publish Date
2003
Start Page
448
End Page
456

Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy.

PURPOSE: To report the incidence of late complications in long-term survivors of very-high-dose thoracic radiotherapy (RT) treated on a prospective clinical trial. METHODS AND MATERIALS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved lymph nodes to a dose of 73.6 Gy at 1.6 Gy twice daily. If the plasma transforming growth factor-beta1 (TGF-beta1) level was normal after 73.6 Gy, additional twice-daily RT was delivered to successively higher total doses until the maximal tolerated dose was reached. Patients within a given dose level were followed for 6 months before escalation to the next dose level was permitted. Late complications were defined according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Thirty-eight patients were enrolled between 1996 and 1999. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGF-beta1 levels. Fourteen patients received dose escalation (80 Gy in 8; 86.4 Gy in 6). Grade 3 or greater late complications occurred in 4 of 24, 1 of 8, and 2 of 6 patients treated to 73.6, 80, and 86.4 Gy, respectively. The corresponding patient numbers with late Grade 4-5 toxicity were 3 of 24, 0 of 6, and 0 of 8. Overall, 7 (18%) of the 38 patients developed Grade 3-5 late toxicity. Nonpulmonary complications predominated (4 of 7). Five (71%) of seven serious complications developed within 11 months after RT; however, the remaining two complications (29%) occurred very late (at 43 and 62 months). The 5-year actuarial risk of late Grade 3-5 complications was 33%. CONCLUSION: Long-term survivors of very-high-dose RT for non-small-cell lung cancer have a significant risk of severe treatment-related complications. At these high dose levels, the predominant toxicity may no longer be pulmonary. All Grade 4-5 complications occurred in patients whose dose was limited to 73.6 Gy because of a persistently elevated TGF-beta1. Thus, persistently elevated plasma TGF-beta1 levels toward the end of RT may identify patients at greatest risk of severe complications.

Authors
Anscher, MS; Marks, LB; Shafman, TD; Clough, R; Huang, H; Tisch, A; Munley, M; Herndon, JE; Garst, J; Crawford, J; Jirtle, RL
MLA Citation
Anscher, MS, Marks, LB, Shafman, TD, Clough, R, Huang, H, Tisch, A, Munley, M, Herndon, JE, Garst, J, Crawford, J, and Jirtle, RL. "Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy." Int J Radiat Oncol Biol Phys 56.4 (July 15, 2003): 988-995.
PMID
12829134
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
56
Issue
4
Publish Date
2003
Start Page
988
End Page
995

Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials.

Delivery of cancer chemotherapy is often limited by myelotoxicity, primarily neutropenia. As part of an effort to create a model to predict the risk of chemotherapy-induced neutropenia, we reviewed the reports of randomized clinical trials with more than 50 patients per arm in early-stage breast cancer (ESBC) and non-Hodgkin's lymphoma (NHL) published between 1990 and 2000. We observed that no hematologic toxicity data were reported in 39% and 34% of the ESBC and NHLtrials, respectively. The remaining trials reported on hematologic toxicity in 16 different ways. When reported, rates of neutropenia, leukopenia, and hematotoxicity varied widely with the same and similar chemotherapy regimens. Dose-intensity data were not reported in 39% and 54% of ESBC and NHL trials, respectively. The majority of the remaining studies reported incomplete dose-intensity data such as percentages of patients completing all cycles or receiving a given percentage of planned dose intensity. Only 28% reported the mean or median relative dose intensity received by patients. Based on this review, we conclude that current practices for reporting chemotherapy treatments are inadequate for describing the risk of chemotherapy to patients or for quantitatively assessing the risk of treatment alternatives. We recommend that standard procedures for documenting and reporting hematologic toxicity and dose intensity in cancer chemotherapy trials be required for publication of chemotherapy trials.

Authors
Dale, DC; McCarter, GC; Crawford, J; Lyman, GH
MLA Citation
Dale, DC, McCarter, GC, Crawford, J, and Lyman, GH. "Myelotoxicity and dose intensity of chemotherapy: reporting practices from randomized clinical trials." J Natl Compr Canc Netw 1.3 (July 2003): 440-454. (Review)
PMID
19761076
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
1
Issue
3
Publish Date
2003
Start Page
440
End Page
454

Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer.

PURPOSE: To review the outcome of patients with limited-stage small-cell lung cancer receiving daily thoracic irradiation (RT) to approximately 60 Gy. METHODS AND MATERIALS: The records of patients treated with RT for limited-stage small-cell lung cancer between 1991 and 1999 at Duke University were retrospectively reviewed. Sixty-five patients were identified who had received continuous course once-daily 1.8-2 Gy fractions to approximately 60 Gy (range 58-66). All patients received chemotherapy (CHT); 32 received concurrent RT/CHT and 33 sequential CHT and then RT. Prophylactic cranial RT was administered to 17 patients. The time from diagnosis to local failure, tumor progression, and death was assessed using actuarial methods. The median follow-up for all patients was 16.7 months and for surviving patients was 29.6 months. The median age was 64 years (range 36-83), and the median Karnofsky performance status was 80 (range 50-100). RESULTS: The 3-year actuarial rate of local failure, progression-free survival, and overall survival was 40%, 25%, and 23%, respectively. One case of acute Grade 3 esophagitis developed. Ten late complications occurred: four pulmonary, two esophageal, two infectious, one leukemia, and one retinal toxicity with prophylactic cranial RT. Six were mild and resolved with treatment. CONCLUSION: CHT plus approximately 60 Gy of once-daily RT for limited-stage small-cell lung cancer was generally well tolerated. The survival rates were less than have been reported using 45 Gy in 1.5-Gy twice-daily fractions (2-year overall survival rate 47% compared with 30% in this study), but may be comparable because fewer than one-half our patients received concurrent CHT/RT and only 26% received prophylactic cranial RT. The relatively low rate of normal tissue morbidity in our patients supports the use of conventional once-daily fractionation to > or = 60 Gy. A randomized trial would be required to compare the outcomes after maximally tolerated dose twice-daily RT vs. maximally tolerated dose daily RT.

Authors
Miller, KL; Marks, LB; Sibley, GS; Clough, RW; Garst, JL; Crawford, J; Shafman, TD
MLA Citation
Miller, KL, Marks, LB, Sibley, GS, Clough, RW, Garst, JL, Crawford, J, and Shafman, TD. "Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer." Int J Radiat Oncol Biol Phys 56.2 (June 1, 2003): 355-359.
PMID
12738309
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
56
Issue
2
Publish Date
2003
Start Page
355
End Page
359

New targeted therapies for non-small-cell lung cancer: a focus on the epidermal growth factor receptor.

Advances in chemotherapy and multimodality treatments of patients with non-small-cell lung cancer (NSCLC) have improved outcomes for these patients over the past decade. Unfortunately, gains have been modest, and new therapeutic strategies are eagerly awaited. Therapies that target receptors vital to the proliferation and survival of cancer cells are particularly attractive areas of research. The epidermal growth factor receptor (EGFR) is widely expressed in NSCLC. Preclinical studies demonstrate that inhibition of EGFR using antibodies or tyrosine kinase inhibitors has led to growth inhibition and tumor regression in a variety of models. A number of agents are currently in clinical trials; the most information in NSCLC is currently available on the tyrosine kinase inhibitors. Phase II trials involving patients with advanced NSCLC and whose disease is progressive after chemotherapy have demonstrated clear clinical benefit. Studies are ongoing, integrating EGFR-targeted therapy with chemotherapy and radiation in patients with earlier stage NSCLC, as well as in chemoprevention. In all of these settings, a further understanding of the biology of EGFR in relationship to other cellular events will be critical in optimizing therapeutic approaches with these novel agents.

Authors
Crawford, J
MLA Citation
Crawford, J. "New targeted therapies for non-small-cell lung cancer: a focus on the epidermal growth factor receptor." J Natl Compr Canc Netw 1 Suppl 1 (January 2003): S78-S86. (Review)
PMID
19795580
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
1 Suppl 1
Publish Date
2003
Start Page
S78
End Page
S86

Delivering optimal adjuvant chemotherapy in primary breast cancer: The role of rHuG-CSF

Most patients with operable breast cancer now receive postoperative medical treatment in the form of adjuvant chemotherapy, hormone manipulation or both. These additional interventions have led to a significant improvement in disease-free survival and overall survival. Clinical trials suggest that total chemotherapy dose delivered and dose intensity both affect long-term clinical outcomes, yet clinical practice audits conducted in Europe and the USA show that dose reductions and delays are widely applied when haematological toxicities such as neutropenia occur. In order to reduce the risk of neutropenic complications and help deliver chemotherapy planned dose on time, targeted use of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in breast cancer patients is recommended. The availability of neutropenia risk prediction models and the first once-per-cycle, fixed-dose rHuG-CSF (pegfilgrastim), will allow more patients to benefit from receiving their planned chemotherapy dose on time, and enable the use of new dose-dense chemotherapy strategies in the adjuvant treatment of primary breast cancer. These hold the prospect of further improving chemotherapy treatment outcomes. © 2003 Elsevier Ltd. All rights reserved.

Authors
Paridaens, R; Lyman, GH; Leonard, R; Crawford, J; Bosly, A; Constenla, M; Jackisch, C; Pettengell, R; Szucs, T
MLA Citation
Paridaens, R, Lyman, GH, Leonard, R, Crawford, J, Bosly, A, Constenla, M, Jackisch, C, Pettengell, R, and Szucs, T. "Delivering optimal adjuvant chemotherapy in primary breast cancer: The role of rHuG-CSF." European Journal of Cancer, Supplement 1.9 (2003): 1-12.
Source
scival
Published In
European Journal of Cancer, Supplement
Volume
1
Issue
9
Publish Date
2003
Start Page
1
End Page
12
DOI
10.1016/S1359-6349(03)00082-X

Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia

Filgrastim (r-metHuG-CSF) was approved in the United States in 1991 for use in decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies treated with myelo-suppressive chemotherapy. Colony-stimulating factors such as filgrastim are a significant advance in the supportive care of patients with cancer. However, because of its short half-life, filgrastim requires daily dosing by injection to maintain its effects on the bone marrow. Pegfilgrastim (Neulasta; Amgen, Thousand Oaks, CA) is a longer-acting, self-regulating form of filgrastim created by the covalent linkage of a 20-kd polyethylene glycol molecule to the N-terminal of the filgrastim molecule. The molecular characteristics of pegfilgrastim result in a longer terminal half-life, making once-per-chemotherapy-cycle administration possible. The results from two randomized double-blind phase III clinical trials in patients with breast cancer treated with myelosuppressive chemotherapy showed that a single dose of pegfilgrastim provides neutrophil support comparable with that provided by an average of II daily injections of filgrastim. Pegfilgrastim has also been shown to be comparable to filgrastim in reducing neutropenic complications in patients treated with chemotherapy for lymphoma. Data from three clinical trials have been presented: a randomized controlled trial in elderly patients treated with CHOP (cyclophos-phamide/doxorubicin/vincristine/prednisone) for relapsed or refractory non-Hodgkin's lymphoma; a randomized controlled trial in patients treated with ESHAP (etoposide/methylprednisolone/cisplatin/cytarabine) for relapsed or refractory lymphoma; and a study in patients with newly diagnosed non-Hodgkin's lymphoma. The safety profile of pegfilgrastim is comparable to that of filgrastim in the clinical settings studied to date. The once-per-cycle administration of pegfilgrastim may improve patient quality of life because it is less disruptive to patients and caregivers, and increase adherence because no doses are missed, thus further advancing the management of chemotherapy-induced neutropenia and its consequences. © 2003 Elsevier Inc. All rights reserved.

Authors
Crawford, J
MLA Citation
Crawford, J. "Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia." Seminars in Oncology 30.4 SUPPL. 13 (2003): 24-30.
PMID
14508717
Source
scival
Published In
Seminars in Oncology
Volume
30
Issue
4 SUPPL. 13
Publish Date
2003
Start Page
24
End Page
30

Safety and efficacy of pegfilgrastim in patients receiving myelosuppressive chemotherapy

The major dose-limiting toxicity associated with myelosuppressive chemotherapy is neutropenia, which can be ameliorated with proactive administration of granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim is a long-acting G-CSF, recently approved by the Food and Drug Administration. The efficacy and safety of pegfilgrastim administered once/chemotherapy cycle have been evaluated in clinical trials involving patients treated with myelosuppressive chemotherapy for breast cancer, lung cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. Two pivotal phase III trials in patients with breast cancer showed that pegfilgrastim is as effective as filgrastim regarding the primary efficacy end point, which was duration of grade 4 (severe) neutropenia in cycle 1 of myelosuppressive chemotherapy. Secondary end points were the frequency of fever with neutropenia (febrile neutropenia), duration of neutropenia in cycles 2-4, depth of the absolute neutrophil count (ANC) nadir, and time to ANC recovery in cycles 1-4. Once/cycle pegfilgrastim 100 pg/kg or 6 mg was as safe and effective as daily filgrastim 5 pg/kg in reducing the frequency and duration of severe neutropenia. A trend toward a greater reduction in the overall frequency of febrile neutropenia with pegfilgrastim was observed. The availability of pegfilgrastim simplifies the use of prophylactic G-CSF, with the potential to increase patient convenience and adherence in management of chemotherapy-induced neutropenia.

Authors
Crawford, J
MLA Citation
Crawford, J. "Safety and efficacy of pegfilgrastim in patients receiving myelosuppressive chemotherapy." Pharmacotherapy 23.8 II (2003): 15S-19S.
PMID
12921218
Source
scival
Published In
Pharmacotherapy
Volume
23
Issue
8 II
Publish Date
2003
Start Page
15S
End Page
19S

Activation of tyrosine kinases in cancer.

Receptor and nonreceptor tyrosine kinases (TKs) have emerged as clinically useful drug target molecules for treating certain types of cancer. Epidermal growth factor receptor (EGFR)-TK is a transmembrane receptor TK that is overexpressed or aberrantly activated in the most common solid tumors, including non-small cell lung cancer and cancers of the breast, prostate, and colon. Activation of the EGFR-TK enzyme results in autophosphorylation, which drives signal transduction pathways leading to tumor growth and malignant progression. Randomized clinical trials of the EGFR-TK inhibitor gefitinib have demonstrated clinical benefits in patients with advanced non-small cell lung cancer whose disease had previously progressed on platinum- and docetaxel-based chemotherapy regimens. Bcr-Abl is a constitutively activated nonreceptor TK enzyme found in the cytoplasm of Philadelphia chromosome-positive leukemia cells. STI571 (imatinib mesylate) inhibits the Bcr-Abl TK, blocks the growth of these leukemia cells, and induces apoptosis. STI571 also inhibits other TKs, including the receptor TK c-kit, which is expressed in gastrointestinal stromal tumors. As TK inhibitors become available for clinical use, new challenges include predicting which patients are most likely to respond to these targeted TK inhibitors. Additional clinical trials are needed to develop the full potential of receptor and nonreceptor TK inhibitors for cancer treatment.

Authors
Vlahovic, G; Crawford, J
MLA Citation
Vlahovic, G, and Crawford, J. "Activation of tyrosine kinases in cancer." Oncologist 8.6 (2003): 531-538. (Review)
PMID
14657531
Source
pubmed
Published In
The oncologist
Volume
8
Issue
6
Publish Date
2003
Start Page
531
End Page
538

Pegfilgrastim: The promise of pegylation fulfilled

Authors
Crawford, J
MLA Citation
Crawford, J. "Pegfilgrastim: The promise of pegylation fulfilled." Annals of Oncology 14.1 (2003): 6-7.
PMID
12488286
Source
scival
Published In
Annals of Oncology
Volume
14
Issue
1
Publish Date
2003
Start Page
6
End Page
7
DOI
10.1093/annonc/mdg036

Anemia and lung cancer.

Authors
Crawford, J
MLA Citation
Crawford, J. "Anemia and lung cancer." Lung Cancer 38 Suppl 3 (December 2002): S75-S78. (Review)
PMID
12468152
Source
pubmed
Published In
Lung Cancer
Volume
38 Suppl 3
Publish Date
2002
Start Page
S75
End Page
S78

Neutrophil growth factors.

A significant advance in the field of neutrophil growth factors has occurred with the commercial availability of pegfilgrastim (Neulasta, Amgen, Thousand Oaks, CA), a new-generation, pegylated filgrastim molecule with a sustained duration of action. Pegylation of filgrastim allows once-per-chemotherapy cycle frequency of administration, in contrast to repeated daily administration of filgrastim. Clinical data from two randomized trials demonstrate equivalence of pegfilgrastim and filgrastim in duration of severe neutropenia and recovery from absolute neutrophil count nadir following myelosuppressive chemotherapy. In addition, secondary endpoint results in both trials suggest an enhanced reduction in the overall incidence of febrile neutropenia with pegfilgrastim. Neutrophil kinetic studies demonstrate steady serum neutrophil levels following pegfilgrastim administration, in contrast to the peak-and-trough neutrophil effects observed following filgrastim administration. Granulocyte colony-stimulating factor (G-CSF) therapy has an antiapoptotic effect on neutrophils, which may be enhanced by continuous serum concentrations of pegfilgrastim. Monocytes possess a G-CSF receptor, and this finding has fueled investigational analysis of the role of G-CSF as a mediator in the host inflammatory response to foreign pathogens. The data demonstrate that depending on the timing of administration, G-CSF may function as a proinflammatory mediator or an anti-inflammatory mediator. It is likely that the early, prophylactic administration of pegfilgrastim creates an environment in which an anti-inflammatory response predominates. Additional investigational studies will be necessary to confirm and better define the mechanism for enhanced benefit of pegfilgrastim over filgrastim. The recent biologic findings of the mechanism of G-CSF therapy reviewed here provide a strong basis from which further research initiatives may be conducted.

Authors
Crawford, J
MLA Citation
Crawford, J. "Neutrophil growth factors." Curr Hematol Rep 1.2 (November 2002): 95-102. (Review)
PMID
12901130
Source
pubmed
Published In
Current hematology reports
Volume
1
Issue
2
Publish Date
2002
Start Page
95
End Page
102

Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431.

PURPOSE: To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer, Cancer and Leukemia Group B (CALGB) conducted a randomized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy. PATIENTS AND METHODS: Eligible patients received four cycles of cisplatin at 80 mg/m(2) on days 1, 22, 43, and 64 with arm 1: gemcitabine 1,250 mg/m(2) on days 1, 8, 22, and 29 and 600 mg/m(2) on days 43, 50, 64, and 71; arm 2: paclitaxel 225 mg/m(2) for 3 hours on days 1 and 22 and 135 mg/m(2) on days 43 and 64; and arm 3: vinorelbine 25 mg/m(2) on days 1, 8, 15, 22, and 29 and 15 mg/m(2) on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43 at 2 Gy/d (total dose, 66 Gy). RESULTS: One hundred seventy-five eligible patients were analyzed. Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2, and 3, respectively. Median survival for all patients was 17 months. One-, 2-, and 3-year survival rates for the patients on the three arms were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%. CONCLUSION: Four cycles of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin can be administered at these doses and schedules. The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy. Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III randomized trial.

Authors
Vokes, EE; Herndon, JE; Crawford, J; Leopold, KA; Perry, MC; Miller, AA; Green, MR
MLA Citation
Vokes, EE, Herndon, JE, Crawford, J, Leopold, KA, Perry, MC, Miller, AA, and Green, MR. "Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431." J Clin Oncol 20.20 (October 15, 2002): 4191-4198.
PMID
12377962
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
20
Publish Date
2002
Start Page
4191
End Page
4198
DOI
10.1200/JCO.2002.03.054

Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials.

BACKGROUND: Prior research has documented the under-representation in clinical trials of older patients with cancer. In part of a larger study to test the magnitude of these barriers to entering eligible older patients with carcinoma of the breast into clinical trials (Cancer and Leukemia Group B [CALGB] trial 9670), barriers to accruing eligible older patients to clinical trials were obtained from the physician's perspective. METHODS: One hundred fifty-six physicians (85% oncologists) who treated patients with breast carcinoma at 10 CALGB institutions completed a questionnaire concerning what they perceived as barriers to enrolling older patients with breast carcinoma on clinical trials and possible interventions that may improve accrual. RESULTS: Physicians' perceptions of the most important barriers to accrual of older patients were: 1) elderly patients have significant comorbid conditions that are not excluded by the protocol but that may affect how they would respond to treatment (16%); elderly patients have difficulty understanding what is required in a complicated treatment trial, resulting in poor compliance (16%); treatment toxicity (14%); and elderly patients often do not meet the eligibility criteria (15%). Oncologists most frequently suggested that the most effective interventions for improving the accrual of elderly patients to trials included making personnel available in the clinic to explain clinical trials to older patients and their families (25%) and providing physicians with educational materials concerning treatment toxicity in the elderly (18%). CONCLUSIONS: Physicians viewed barriers to accruing older patients with breast carcinoma to clinical trials as multidimensional, with the most important involving protocol requirements, treatment specific issues, and older patients' medical and cognitive characteristics. Thus, a variety of interventions would be needed to improve accrual of older patients to clinical trials, including increasing physicians' knowledge concerning treatment toxicity in the elderly, simplifying protocol requirements, and reducing treatment toxicity.

Authors
Kornblith, AB; Kemeny, M; Peterson, BL; Wheeler, J; Crawford, J; Bartlett, N; Fleming, G; Graziano, S; Muss, H; Cohen, HJ; Cancer and Leukemia Group B,
MLA Citation
Kornblith, AB, Kemeny, M, Peterson, BL, Wheeler, J, Crawford, J, Bartlett, N, Fleming, G, Graziano, S, Muss, H, Cohen, HJ, and Cancer and Leukemia Group B, . "Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials." Cancer 95.5 (September 1, 2002): 989-996.
PMID
12209681
Source
pubmed
Published In
Cancer
Volume
95
Issue
5
Publish Date
2002
Start Page
989
End Page
996
DOI
10.1002/cncr.10792

Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia: Cancer and Leukemia Group B study 9420.

PURPOSE: The purpose of the study is to investigate the tolerability of interleukin 2 (IL-2) after intensive chemotherapy in elderly acute myeloid leukemia (AML) patients in first complete remission (CR). EXPERIMENTAL DESIGN: AML patients > or =60 years in CR after induction and consolidation chemotherapy on Cancer and Leukemia Group B study 9420 were eligible if they had neutrophils > or =1 x 10(9)/liters and platelets > or =75 x 10(9)/liters. Patients received low-dose IL-2 (1 x 10(6) IU/m(2)/day s.c. for 90 days) or low-dose IL-2 with intermediate pulse doses (6-12 x 10(6) IU/m(2)/day s.c. for 3 days) every 14 days (maximum five pulses). In a subset of patients, we investigated the expression of NKG2D ligands by leukemic cells because they are likely important mediators of natural killer cytotoxicity. RESULTS: Of 35 CR patients receiving IL-2, 34 were evaluable for toxicity. Median age was 67 (range, 60-76) years. Thirteen of 16 patients receiving low-dose IL-2 completed the planned therapy, and 11 of 18 who also received intermediate pulse dose IL-2 therapy completed all five pulses. The spectrum of toxicity in both groups was similar, with predominantly grade 1-2 fatigue, fever, injection site reactions, nausea, anemia, and thrombocytopenia. Grade 3-4 hematological and nonhematological toxicity were more frequent in patients also receiving intermediate pulse dose IL-2 therapy. Grade 3-4 fatigue and hematological toxicity, although uncommon, were the major causes for discontinuing or attenuating therapy. In 8 cases, mRNA for one or more NKG2D ligands was detected in leukemic cells obtained at diagnosis before treatment. CONCLUSIONS: Low-dose IL-2, with or without intermediate pulse dose therapy, given immediately after chemotherapy in first CR to elderly AML patients is well tolerated. Expression of NKG2D ligands by leukemic cells was detected in the majority of cases tested and should be assessed for correlation with response to IL-2 in future studies.

Authors
Farag, SS; George, SL; Lee, EJ; Baer, M; Dodge, RK; Becknell, B; Fehniger, TA; Silverman, LR; Crawford, J; Bloomfield, CD; Larson, RA; Schiffer, CA; Caligiuri, MA
MLA Citation
Farag, SS, George, SL, Lee, EJ, Baer, M, Dodge, RK, Becknell, B, Fehniger, TA, Silverman, LR, Crawford, J, Bloomfield, CD, Larson, RA, Schiffer, CA, and Caligiuri, MA. "Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia: Cancer and Leukemia Group B study 9420." Clin Cancer Res 8.9 (September 2002): 2812-2819.
PMID
12231521
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
8
Issue
9
Publish Date
2002
Start Page
2812
End Page
2819

Recombinant human erythropoietin in cancer-related anemia. Review of clinical evidence.

The clinical development of recombinant human erythropoietin (rHuEPO) has had a remarkable impact on the clinical practice of oncology. A decade ago, randomized, placebo-controlled trials in anemic cancer patients demonstrated that rHuEPO resulted in an improvement in hemoglobin and hematocrit, a reduction in transfusion requirements, and improvement in quality-of-life (QOL) end points. Based on these trials, recombinant erythropoietin was approved for the treatment of anemia in patients with nonmyeloid malignancies in whom the anemia was caused by the effect of chemotherapy. The clinical indication was to decrease the needfor transfusion in patients for whom anemia was not due to other reversible causes. Despite this broad indication, the incorporation of rHuEPO in clinical practice was limited because of a variety of factors, including physician perception that mild-to-moderate anemia in the cancer patient was generally asymptomatic and did not warrant intervention. Subsequently, three large open-label, prospective trials of recombinant erythropoietin were performed in the community setting in anemic cancer chemotherapy patients. All three trials replicated the results of the original randomized study, but with a much larger database of more than 7,000 patients. Importantly, these trials were able to define the major impact of hemoglobin level on quality of life. Patients on these trials who improved their hemoglobin > 2 g/dL or achieved a hemoglobin > or = 12 g/ dL had the greatest improvement in symptoms of energy, activities of daily living, and overall quality of life. Furthermore, a once-per-week dosing schedule was found to be comparable to three-times-weekly administration of rHuEPO. A European randomized, placebo-controlled trial confirmed these QOL results, and a meta-analysis of other randomized clinical trials firmly supports the role of erythropoietin therapy in improving hemoglobin levels and reducing transfusion requirements. Based on this aggregate of data, the use of erythropoietin in the treatment of mild-to-moderate anemia has become a standard of care. These studies have also expanded our understanding of the problem of fatigue and the study of interventions that can improve quality of life for cancer patients.

Authors
Crawford, J
MLA Citation
Crawford, J. "Recombinant human erythropoietin in cancer-related anemia. Review of clinical evidence." Oncology (Williston Park) 16.9 Suppl 10 (September 2002): 41-53. (Review)
PMID
12380954
Source
pubmed
Published In
Oncology
Volume
16
Issue
9 Suppl 10
Publish Date
2002
Start Page
41
End Page
53

Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy.

BACKGROUND: Hemoglobin increases have been associated with quality of life (QOL) improvements in anemic cancer patients treated with epoetin alfa, but intervention generally has been reserved for symptomatic anemia or hemoglobin < 10 g/dL. Relationships among hemoglobin, functional status, and patient reported QOL have not been well characterized. METHODS: Data from two open-label, community-based trials of epoetin alfa therapy that enrolled 4382 anemic cancer patients undergoing chemotherapy were used to evaluate the relationship between hemoglobin changes and QOL changes. The authors measured QOL using the Linear Analog Scale Assessment (LASA) and the more detailed, disease-specific Functional Assessment of Cancer Therapy-Anemia (FACT-An) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases (1 g/dL increments). RESULTS: Cross-sectional analyses showed a nonlinear relationship and significant positive correlation between high hemoglobin levels and high LASA and FACT-An scores (r = 0.25 and 0.29, respectively, P < 0.01). Patients with hemoglobin increases of > or = 2 g/dL reported statistically significant improvements in five FACT-An items selected a priori specifically to reflect functional capacity. An incremental analysis used regression methods to identify the longitudinal relationship between incremental changes in hemoglobin and QOL scores. This relationship was found to be nonlinear, with the maximum QOL gain occurring at a hemoglobin level of 12 g/dL (range, 11-13 g/dL). Patients with low baseline QOL scores and longer time periods between baseline and final QOL assessments experienced significantly (P < 0.05) greater increases in overall QOL. Progressive disease at baseline, change in disease status from baseline to end of study, and increase in self-reported pain or nausea all had significant (P < 0.05) negative effects on QOL scores. CONCLUSIONS: A direct relationship exists between hemoglobin increases during epoetin alfa therapy and corresponding QOL improvements in cancer patients receiving chemotherapy across the clinically relevant hemoglobin range of 8-14 g/dL. These data suggest that the maximal incremental gain in QOL occurs when hemoglobin is in the range of 11-13 g/dL.

Authors
Crawford, J; Cella, D; Cleeland, CS; Cremieux, P-Y; Demetri, GD; Sarokhan, BJ; Slavin, MB; Glaspy, JA
MLA Citation
Crawford, J, Cella, D, Cleeland, CS, Cremieux, P-Y, Demetri, GD, Sarokhan, BJ, Slavin, MB, and Glaspy, JA. "Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy." Cancer 95.4 (August 15, 2002): 888-895.
PMID
12209734
Source
pubmed
Published In
Cancer
Volume
95
Issue
4
Publish Date
2002
Start Page
888
End Page
895
DOI
10.1002/cncr.10763

Clinical uses of pegylated pharmaceuticals in oncology.

A number of agents that are used in the treatment of cancer have a suboptimal pharmacokinetic profile that necessitates prolonged or repetitive administration. Pegylation of these agents may help overcome these shortcomings without compromising the agents' efficacy. Several such pegylated agents have now been developed and evaluated in patients with oncology-related disorders. Pegfilgrastim (a pegylated form of filgrastim) has shown efficacy and tolerability that are at least equivalent to those of filgrastim in patients with chemotherapy-induced neutropenia and, unlike unmodified filgrastim, is effective with only one administration per chemotherapy cycle. Other promising pegylated agents are pegylated liposomal doxorubicin, which appears to be more effective and less cardiotoxic than unmodified or liposome-encapsulated doxorubicin, and peginterferon alpha-2a, as once-weekly treatment for renal cell carcinoma. Pegylated agents are likely to be more convenient for patients than the standard formulations, and the improved pharmacokinetics will enhance the clinical utility of these agents.

Authors
Crawford, J
MLA Citation
Crawford, J. "Clinical uses of pegylated pharmaceuticals in oncology." Cancer Treat Rev 28 Suppl A (April 2002): 7-11. (Review)
PMID
12173409
Source
pubmed
Published In
Cancer Treatment Reviews
Volume
28 Suppl A
Publish Date
2002
Start Page
7
End Page
11

Clinical benefits of epoetin alfa therapy in patients with lung cancer.

A retrospective subset analysis of anemic lung cancer patients who participated in three large, multicenter, community-based studies of 3-times-weekly (TIW) or once-weekly (QW) recombinant human erythropoietin (r-HuEPO, epoetin alfa) as an adjunct to chemotherapy was conducted. Patients were treated with epoetin alfa 150 U/kg in the first TIW study and with 10,000 U subcutaneously in the other study, with doubling of the dose if hemoglobin (Hb) response was inadequate. Patients in the QW study received epoetin alfa 40,000 U subcutaneously, which could be increased to 60,000 U. The maximum treatment duration for all three studies was 16 weeks. A total of 1748 lung cancer patients were evaluable for hematopoietic response; 1298 were evaluable for analyses of energy and 1300 were evaluable for analyses of activity and overall quality of life (QOL), as measured by the linear analogue scale assessment (LASA). Within 2 months of therapy, TIW and QW epoetin alfa therapy resulted in significant increases in Hb levels, decreases in transfusion requirements, and improvements in self-reported LASA scores. Increased Hb levels and reduced transfusion rates were demonstrated in the individual studies and in the analysis of data pooled from all three studies. Improvements in QOL parameters were significantly correlated with increased Hb levels. Epoetin alfa was well tolerated in all studies. The clinical benefits and safety profiles of the TIW and the QW schedules appear to be similar. In addition, the QW schedule provides greater convenience to patients and physicians alike. Given the high incidence of anemia and transfusion utilization in patients presenting with lung cancer, epoetin alfa is an effective strategy for correcting anemia in these patients, thereby improving their energy levels, activity levels, and overall QOL.

Authors
Crawford, J; Demetri, GD; Gabrilove, JL; Blasi, MV; Sarokhan, BJ; Glaspy, J
MLA Citation
Crawford, J, Demetri, GD, Gabrilove, JL, Blasi, MV, Sarokhan, BJ, and Glaspy, J. "Clinical benefits of epoetin alfa therapy in patients with lung cancer." Clin Lung Cancer 3.3 (February 2002): 180-190.
PMID
14662041
Source
pubmed
Published In
Clinical lung cancer
Volume
3
Issue
3
Publish Date
2002
Start Page
180
End Page
190

Consensus on medical treatment of non-small cell lung cancer

Authors
Akehurst, RL; Beinert, T; Crawford, J; Crino, L; Debus, J; Eckersberger, F; Fischer, J; Georgoulias, V; Gridelli, C; Hirsh, FR; Jassem, J; Kosmidis, P; Krainer, M; Krzakowski, M; Manegold, C; Niklinski, J; Pirker, R; Pujol, JL; Scagliotti, G; Thatcher, N; Tomek, S; Tonato, M; Zandwijk, NV; Zielinski, CC; Zöchbauer, S; Zwitter, M
MLA Citation
Akehurst, RL, Beinert, T, Crawford, J, Crino, L, Debus, J, Eckersberger, F, Fischer, J, Georgoulias, V, Gridelli, C, Hirsh, FR, Jassem, J, Kosmidis, P, Krainer, M, Krzakowski, M, Manegold, C, Niklinski, J, Pirker, R, Pujol, JL, Scagliotti, G, Thatcher, N, Tomek, S, Tonato, M, Zandwijk, NV, Zielinski, CC, Zöchbauer, S, and Zwitter, M. "Consensus on medical treatment of non-small cell lung cancer." Lung Cancer 38.3 SUPPL. (2002): S3-S7.
PMID
12468137
Source
scival
Published In
Lung Cancer
Volume
38
Issue
3 SUPPL.
Publish Date
2002
Start Page
S3
End Page
S7

Pegfilgrastim for the prevention of chemotherapy-induced neutropenic complications, with dosing once per chemotherapy cycle

In the past 10 years, colony-stimulating factors (CSFs) such as filgrastim have been used successfully to reduce the clinical impact of chemotherapy-induced neutropenia. The recent availability of pegfilgrastim (Neulasta™), a next-generation pegylated filgrastim molecule with a sustained duration of action, is a significant advance in the management of chemotherapy-induced neutropenia. In contrast to repeated daily injections of filgrastim, pegfilgrastim is given only once per chemotherapy cycle in a single 6-mg fixed dose. Clinical data from two randomized trials demonstrated the equivalence of pegfilgrastim and filgrastim in reducing the duration of severe neutropenia following myelosuppressive chemotherapy. In addition, a retrospective analysis of both trials suggested an improved (approximately 50% greater) reduction in the overall incidence of febrile neutropenia with pegfilgrastim compared to filgrastim. A review of recent data on the cellular effects of CSFs provides insight into the possible mechanisms by which pegfilgrastim might produce this enhanced clinical benefit. The availability of pegfilgrastim, along with a greater understanding of the risk factors for neutropenic complications and their economic and quality-of-life consequences, offers simplified and possibly more cost-effective management of chemotherapy-induced neutropenia.

Authors
Crawford, J
MLA Citation
Crawford, J. "Pegfilgrastim for the prevention of chemotherapy-induced neutropenic complications, with dosing once per chemotherapy cycle." Today's Therapeutic Trends 20.4 (2002): 393-418.
Source
scival
Published In
Today's Therapeutic Trends
Volume
20
Issue
4
Publish Date
2002
Start Page
393
End Page
418

Clinical benefits of pegylated proteins in oncology

In summary, the improved pharmacology, novel effects, and clinical benefits of pegylated drugs offer oncologists a number of new treatment options that can result in better patient care, greater patient adherence, and improved quality of life.

Authors
Crawford, J
MLA Citation
Crawford, J. "Clinical benefits of pegylated proteins in oncology." Cancer Treatment Reviews 28.SUPPL. A (2002): 1-2.
PMID
12173406
Source
scival
Published In
Cancer Treatment Reviews
Volume
28
Issue
SUPPL. A
Publish Date
2002
Start Page
1
End Page
2
DOI
10.1053/ctrv.2002.0251

Pegfilgrastim administered once per cycle reduces incidence of chemotherapy-induced neutropenia.

Neutropenia is a common and potentially dangerous adverse effect of cancer chemotherapy. It also often necessitates a reduction or delay in dose, thus compromising efficacy. The human granulocyte colony-stimulating factor filgrastim has been proven to have a good safety profile and to be effective in accelerating neutrophil recovery and reducing the incidence of infections following myelosuppressive chemotherapy. However, its short serum half-life necessitates daily administration. Pegylated filgrastim (pegfilgrastim) was developed by attaching a polyethylene glycol moiety to the filgrastim protein. Pegfilgrastim binds to the same cell surface receptor on neutrophils and their precursors as filgrastim and stimulates the proliferation and differentiation of neutrophils through the same mechanism. However, because of the pegylation, it is minimally cleared by the kidneys and has a much longer serum half-life. Furthermore, its clearance is neutrophil dependent and thus 'self-regulated'. Pegfilgrastim is administered as a single subcutaneous injection per cycle of chemotherapy. In clinical trials it has been shown to be comparable in efficacy to filgrastim in decreasing the incidence of infection as manifested by febrile neutropenia following chemotherapy. Its safety profile and tolerability are similar to those of filgrastim.

Authors
Crawford, J
MLA Citation
Crawford, J. "Pegfilgrastim administered once per cycle reduces incidence of chemotherapy-induced neutropenia." Drugs 62 Suppl 1 (2002): 89-98. (Review)
PMID
12479597
Source
pubmed
Published In
Drugs
Volume
62 Suppl 1
Publish Date
2002
Start Page
89
End Page
98

Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.

PURPOSE: The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGFbeta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. PATIENT AND METHODS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which < or = one grade 4 (life-threatening) late toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities occurred. RESULTS: Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities. CONCLUSION: It is feasible to use plasma TGFbeta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy.

Authors
Anscher, MS; Marks, LB; Shafman, TD; Clough, R; Huang, H; Tisch, A; Munley, M; Herndon, JE; Garst, J; Crawford, J; Jirtle, RL
MLA Citation
Anscher, MS, Marks, LB, Shafman, TD, Clough, R, Huang, H, Tisch, A, Munley, M, Herndon, JE, Garst, J, Crawford, J, and Jirtle, RL. "Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation." J Clin Oncol 19.17 (September 1, 2001): 3758-3765.
PMID
11533099
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
19
Issue
17
Publish Date
2001
Start Page
3758
End Page
3765
DOI
10.1200/JCO.2001.19.17.3758

Carboplatin/etoposide/paclitaxel in the treatment of patients with extensive small-cell lung cancer.

The purpose of this study was to examine the safety and efficacy of carboplatin/etoposide/paclitaxel in patients with untreated stage IV non-small-cell lung cancer (NSCLC) and extensive small-cell lung cancer (SCLC). Carboplatin was administered intravenously (i.v.) at an area under the curve (AUC) of 6 with etoposide at either 80 or 100 mg/m2 i.v. days 1-3 and paclitaxel at 175 or 200 mg/m2 i.v. over 3 hours along with 5 g/kg of granulocyte colony-stimulating factor subcutaneously on days 4-18, repeated every 3 weeks for 6 courses. Thirty-one patients (five NSCLC and 26 SCLC) entered into this phase I study. The median age was 63 (range, 42 to 74 years), with 24 males and seven females. The recommended dose level for phase II testing was carboplatin AUC = 6, etoposide 80 mg/m2 days 1-3, and paclitaxel 175 mg/m2 over 3 hours. With seven patients at this level, 14% had grade 4 neutropenia, 14% had grade 4 thrombocytopenia, none had grade 2/3 neurotoxicity, and no toxic deaths occurred. One of five (20%) patients with NSCLC responded, and 19 of 22 (86%) evaluable SCLC patients experienced a response to therapy. SCLC patients had a median survival of 10 months. The combination of carboplatin/etoposide/paclitaxel has significant activity with acceptable toxicity in patients with extensive SCLC.

Authors
Niell, HB; Perry, MC; Clamon, G; Crawford, J; Miller, AA; Herndon, J; Green, MR
MLA Citation
Niell, HB, Perry, MC, Clamon, G, Crawford, J, Miller, AA, Herndon, J, and Green, MR. "Carboplatin/etoposide/paclitaxel in the treatment of patients with extensive small-cell lung cancer." Clin Lung Cancer 2.3 (February 2001): 204-209.
PMID
14700479
Source
pubmed
Published In
Clinical lung cancer
Volume
2
Issue
3
Publish Date
2001
Start Page
204
End Page
209

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

The maximum tolerated dose of conformal radiation therapy delivered at 1.6 Gy bid is being assessed in patients with unresectable stage IIB-IIIB non-small cell lung cancer who have been treated with induction regimens consisting of carboplatin plus paclitaxel or carboplatin plus vinorelbine. Data from the early stages of this parallel phase I study show that the two induction regimens are similar in toxicity and that both induce partial responses in 45% of patients. Both regimens can be followed by conformal radiotherapy using an accelerated hyperfractionated schedule to a dose of at least 80 Gy without experiencing unacceptable toxicity. Key morbidity observed thus far has involved the esophagus. Further cohorts of patients will receive higher doses of conformal radiotherapy (in 6.4 Gy increments) until the maximum tolerated dose is reached.

Authors
Socinski, MA; Marks, LB; Garst, J; Sibley, GS; Blackstock, W; Turrisi, A; Herndon, J; Zhou, S; Anscher, M; Crawford, J; Shafman, T; Rosenman, J
MLA Citation
Socinski, MA, Marks, LB, Garst, J, Sibley, GS, Blackstock, W, Turrisi, A, Herndon, J, Zhou, S, Anscher, M, Crawford, J, Shafman, T, and Rosenman, J. "Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium." Oncologist 6 Suppl 1 (2001): 20-24.
PMID
11182001
Source
pubmed
Published In
The oncologist
Volume
6 Suppl 1
Publish Date
2001
Start Page
20
End Page
24

Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy.

PURPOSE: To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with non-small-cell lung cancer were randomized to receive daily filgrastim (5 microg/kg/d) or a single injection of SD/01 (30, 100, or 300 microg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts. CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.

Authors
Johnston, E; Crawford, J; Blackwell, S; Bjurstrom, T; Lockbaum, P; Roskos, L; Yang, BB; Gardner, S; Miller-Messana, MA; Shoemaker, D; Garst, J; Schwab, G
MLA Citation
Johnston, E, Crawford, J, Blackwell, S, Bjurstrom, T, Lockbaum, P, Roskos, L, Yang, BB, Gardner, S, Miller-Messana, MA, Shoemaker, D, Garst, J, and Schwab, G. "Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy." J Clin Oncol 18.13 (July 2000): 2522-2528.
PMID
10893282
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
18
Issue
13
Publish Date
2000
Start Page
2522
End Page
2528
DOI
10.1200/JCO.2000.18.13.2522

Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P =.001 and P =.036, respectively). Patients who received docetaxel had a longer time to progression (P =.046, by log-rank test) and a greater progression-free survival at 26 weeks (P =.005, by chi(2) test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P =.025, by chi(2) test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

Authors
Fossella, FV; DeVore, R; Kerr, RN; Crawford, J; Natale, RR; Dunphy, F; Kalman, L; Miller, V; Lee, JS; Moore, M; Gandara, D; Karp, D; Vokes, E; Kris, M; Kim, Y; Gamza, F; Hammershaimb, L
MLA Citation
Fossella, FV, DeVore, R, Kerr, RN, Crawford, J, Natale, RR, Dunphy, F, Kalman, L, Miller, V, Lee, JS, Moore, M, Gandara, D, Karp, D, Vokes, E, Kris, M, Kim, Y, Gamza, F, and Hammershaimb, L. "Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group." J Clin Oncol 18.12 (June 2000): 2354-2362.
PMID
10856094
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
18
Issue
12
Publish Date
2000
Start Page
2354
End Page
2362
DOI
10.1200/JCO.2000.18.12.2354

2000 Update of recommendations for the use of hematopoietic colony-stimulating factors: Evidence-based, clinical practice guidelines

Authors
Ozer, H; Armitage, JO; Bennett, CL; Crawford, J; Demetri, GD; Pizzo, PA; Schiffer, CA; Smith, TJ; Somlo, G; Wade, JC; III, JLW; Winn, RJ; Wozniak, AJ; Somerfield, MR
MLA Citation
Ozer, H, Armitage, JO, Bennett, CL, Crawford, J, Demetri, GD, Pizzo, PA, Schiffer, CA, Smith, TJ, Somlo, G, Wade, JC, III, JLW, Winn, RJ, Wozniak, AJ, and Somerfield, MR. "2000 Update of recommendations for the use of hematopoietic colony-stimulating factors: Evidence-based, clinical practice guidelines." Journal of Clinical Oncology 18.20 (2000): 3558-3585.
PMID
11032599
Source
scival
Published In
Journal of Clinical Oncology
Volume
18
Issue
20
Publish Date
2000
Start Page
3558
End Page
3585

Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy.

Mucositis, the inflammation and necrosis of mucosal membranes, is a serious and debilitating consequence of many cancer therapies. We were interested in the potential role of filgrastim (recombinant methionyl human granulocyte colony-stimulating factor, r-metHuG-CSF) in the reduction of mucositis. Patients with newly diagnosed small-cell lung cancer (SCLC) were treated with CAE chemotherapy (cyclophosphamide, doxorubicin, and etoposide) and placebo or filgrastim. If patients had an episode of febrile neutropenia, they received unblinded filgrastim in subsequent CAE cycles. Oral mucositis was considered to have occurred if a patient reported any clinical sign or symptom of oral mucositis with or without oral candidiasis. Oral mucositis was analyzed using the unadjusted chi-square test, and time to first episode of mucositis was analyzed using the stratified log-rank test as well as the Cox proportional hazards regression model. During cycle 1, placebo-treated patients had more episodes of mucositis (47%) compared with those patients randomized to filgrastim (28%). Across all cycles of treatment, 70% of placebo-treated patients experienced mucositis, compared with 53% of patients randomized to filgrastim. A significant reduction in the incidence of chemotherapy-related oral mucositis occurred across multiple cycles of treatment in patients treated with filgrastim.

Authors
Crawford, J; Tomita, DK; Mazanet, R; Glaspy, J; Ozer, H
MLA Citation
Crawford, J, Tomita, DK, Mazanet, R, Glaspy, J, and Ozer, H. "Reduction of oral mucositis by filgrastim (r-metHuG-CSF) in patients receiving chemotherapy." Cytokines Cell Mol Ther 5.4 (December 1999): 187-193.
PMID
10850381
Source
pubmed
Published In
Cytokines, Cellular and Molecular Therapy
Volume
5
Issue
4
Publish Date
1999
Start Page
187
End Page
193

Hematopoietic growth factors in cancer chemotherapy.

Hematopoietic growth factors have made a significant impact on the treatment of cancer, primarily in the prevention of infections associated with chemotherapy-induced neutropenia, in progenitor cell transplantation, in chemotherapy-induced thrombocytopenia, and in chemotherapy-induced anemia. As seen with this review, our basic understanding of hematopoietic growth factors and their clinical potential continue to expand. Work will need to continue, especially with the new thrombopoietic factors, megakaryocyte growth and developing factor, thrombopoietin, and IL-11, to fully categorize their biology and clinical characteristics.

Authors
Crawford, J; Foote, M; Morstyn, G
MLA Citation
Crawford, J, Foote, M, and Morstyn, G. "Hematopoietic growth factors in cancer chemotherapy." Cancer chemotherapy and biological response modifiers 18 (January 1999): 250-267. (Review)
PMID
10800487
Source
epmc
Published In
Cancer chemotherapy and biological response modifiers
Volume
18
Publish Date
1999
Start Page
250
End Page
267

Cost effectiveness, quality-adjusted life-years and supportive care: Recombinant human erythropoietin as a treatment of cancer-associated anaemia

Objective: To measure the cost effectiveness of a supportive care intervention when the no-treatment option is unrealistic in an analysis of recombinant human erythropoietin (epoetin) treatment for anaemic patients with cancer undergoing chemotherapy. Further, to assess whether quality- adjusted life-years (QALYs) can provide the basis for an appropriate measure of the value of supportive care interventions. Design: A modelling study drawing cost and effectiveness assumptions from a literature review and from 3 US clinical trials involving more than 4500 patients with cancer who were treated with chemotherapy, radiotherapy, epoetin and blood transfusions as needed under standard care for patients with cancer. Main outcome measures and results: When compared with transfusions, epoetin is cost effective under varying assumptions, whether effectiveness is measured by haemoglobin level or quality of life. Specifically, under a base-case scenario, the effectiveness resulting from $US1 spent on standard care can be achieved with only $US0.81 of epoetin care. Due in part to the health-state dependence of the significance patients attach to incremental changes in their responses on the linear analogue scale, cost per QALY results are ambiguous in this supportive care context. Conclusions: Under a broad range of plausible assumptions, epoetin can be used cost effectively in the treatment of anaemic patients with cancer. Further, QALYs have limited applicability here because, as a short term supportive treatment, epoetin enhances the quality but not the length of life. Future research would benefit from the establishment of consistent values for quality-of-life changes across patients and health status, and the extension of the QALY framework to supportive care.

Authors
Cremieux, P-Y; Finkelstein, SN; Berndt, ER; Crawford, J; Slavin, MB
MLA Citation
Cremieux, P-Y, Finkelstein, SN, Berndt, ER, Crawford, J, and Slavin, MB. "Cost effectiveness, quality-adjusted life-years and supportive care: Recombinant human erythropoietin as a treatment of cancer-associated anaemia." PharmacoEconomics 16.5 I (1999): 459-472.
PMID
10662393
Source
scival
Published In
PharmacoEconomics
Volume
16
Issue
5 I
Publish Date
1999
Start Page
459
End Page
472
DOI
10.2165/00019053-199916050-00004

Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer

Purpose: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non-small- cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patients and Methods: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m2) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m2) after CPT-11 administration on day 1. Results: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The 1- year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32.7%) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%). The study design led to preferential modification of CPT-11 doses, resulting in CPT-11 dose attenuations to ≤ 40 mg/m2 in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies. Conclusion: CPT-11/cisplatin is an active combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions to exploit more directly the therapeutic synergy of these agents.

Authors
DeVore, RF; Johnson, DH; Crawford, J; Garst, J; Dimery, IW; Eckardt, J; Eckhardt, SG; Elfring, GL; Schaaf, LJ; Hanover, CK; Miller, LL
MLA Citation
DeVore, RF, Johnson, DH, Crawford, J, Garst, J, Dimery, IW, Eckardt, J, Eckhardt, SG, Elfring, GL, Schaaf, LJ, Hanover, CK, and Miller, LL. "Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer." Journal of Clinical Oncology 17.9 (1999): 2710-2720.
PMID
10561345
Source
scival
Published In
Journal of Clinical Oncology
Volume
17
Issue
9
Publish Date
1999
Start Page
2710
End Page
2720

Hematopoietic growth factors in the reduction of chemotherapeutic toxicity.

Neutropenia is the most common dose-limiting toxicity of conventional chemotherapy. The colony-stimulating factors (CSFs), granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, stimulate proliferation and maturation of myeloid progenitors and have been effective in reducing neutropenia and its complications. The primary use of CSFs in patients receiving chemotherapy for small cell lung cancer has resulted in a reduction in the incidence of febrile neutropenia, a decrease in the duration of grade IV neutropenia, and a reduction in hospitalization time and antibiotic use. Although CSF use allows for higher dose intensity, a survival benefit has not been proven. The use of CSFs after the occurrence of neutropenic fever decreases the duration of grade IV neutropenia, but effects on hospitalization and antibiotic use are less well-defined. The therapeutic use of CSFs in the setting of established neutropenia, regardless of the presence or absence of fever, is not supported in the literature. The administration of CSFs to patients with acute myeloid leukemia is safe in that no trial has demonstrated evidence of leukemic stimulation with these drugs. As in other settings, the duration of neutropenia is shortened if CSFs are used postchemotherapy with evidence of clinical benefit. CSFs also decrease chemotherapeutic toxicity via other mechanisms. The use of G-CSF reduces the incidence of mucositis, in normal donors enhances the yield of leukapheresis for granulocyte transfusion, and is beneficial in the autologous transplant setting. These effects of CSFs in mitigating chemotherapeutic toxicity are reviewed.

Authors
Johnston, EM; Crawford, J
MLA Citation
Johnston, EM, and Crawford, J. "Hematopoietic growth factors in the reduction of chemotherapeutic toxicity." Semin Oncol 25.5 (October 1998): 552-561. (Review)
PMID
9783594
Source
pubmed
Published In
Seminars in Oncology
Volume
25
Issue
5
Publish Date
1998
Start Page
552
End Page
561

A study of filgrastim (rG-CSF) priming of etoposide/cisplatin in advanced non-small cell lung cancer.

A previous phase II study (CALGB 9132) of etoposide/cisplatin + rG-CSF in patients with advanced non-small cell lung cancer (NSCLC) showed a marked difference in the absolute neutrophil count (ANC) nadirs between courses 1 and 2. Median ANC nadirs for courses 1 and 2 were 200 and 2500, respectively, suggesting a priming effect for rG-CSF. The present study was designed to determine whether rG-CSF given prior to the first cycle of chemotherapy would decrease the severity and duration of neutropenia. Twelve patients with stage IIIB or IV NSCLC and performance status 0-1 received rG-CSF 5 microg/kg for 5 consecutive days starting 7 days before treatment with etoposide 200 mg/m2 on days 1-3 and cisplatin 35 mg/m2 on days 1-3, repeated every 3 weeks. Patients also received rG-CSF 5 microg/kg s.c. day 4 to postnadir ANC > 10,000. The median WBC nadir, ANC nadir, and platelet nadir after the first cycle of chemotherapy in the historical group (CALGB 9132) were 1300 cells/microl, 200 cells/microl, and 80,000 cells/microl, respectively. In the present study, the median WBC nadir, ANC nadir, and platelet nadir were 1300 cells/microl, 144 cells/microl, and 56,000 cells/microl, respectively. The median time for ANC to reach 10,000 cells/microl was 15 days in both the historical and the present study. For course 2, the WBC, ANC, platelet nadirs, and duration of grade 4 neutropenia were 2600, 1450, 70,000, and 0 days, respectively. This study failed to show a priming effect for rG-CSF when given in this dose and schedule.

Authors
Mehdi, SA; Perry, MC; Herndon, JE; Crawford, J; Young, R; Graziano, SL
MLA Citation
Mehdi, SA, Perry, MC, Herndon, JE, Crawford, J, Young, R, and Graziano, SL. "A study of filgrastim (rG-CSF) priming of etoposide/cisplatin in advanced non-small cell lung cancer." J Interferon Cytokine Res 18.8 (August 1998): 623-627.
PMID
9726444
Source
pubmed
Published In
Journal of Interferon & Cytokine Research
Volume
18
Issue
8
Publish Date
1998
Start Page
623
End Page
627
DOI
10.1089/jir.1998.18.623

Tumor lysis syndrome and acute renal failure after treatment of non-small-cell lung carcinoma with combination irinotecan and cisplatin.

Tumor lysis syndrome, characterized by multiple metabolic abnormalities resulting from abrupt tumor cell death and release of intracellular constituents and metabolites, is most commonly associated with the treatment of highly chemotherapy-sensitive lymphoid and leukemic neoplasms. The authors report a case of tumor lysis syndrome accompanied by acute renal failure that occurred in a patient with stage IV non-small-cell lung cancer who was treated with topoisomerase I inhibitor, irinotecan, and cisplatin. Consistent with the rapid tumor lysis, an objective, marked, early clinical response was observed. Attention to adequate hydration, electrolytes, and renal function should be given to outpatients with non-small-cell lung cancer who receive newer chemotherapeutic agents that have greater efficacy toward this group of tumors.

Authors
Persons, DA; Garst, J; Vollmer, R; Crawford, J
MLA Citation
Persons, DA, Garst, J, Vollmer, R, and Crawford, J. "Tumor lysis syndrome and acute renal failure after treatment of non-small-cell lung carcinoma with combination irinotecan and cisplatin." Am J Clin Oncol 21.4 (August 1998): 426-429.
PMID
9708649
Source
pubmed
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
21
Issue
4
Publish Date
1998
Start Page
426
End Page
429

Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly.

PURPOSE: To determine if there is an increased prevalence of monoclonal gammopathy in elderly blacks compared with whites, analogous to the difference in incidence of multiple myeloma reported for the two racial groups and to confirm age and gender relationships. PATIENTS AND METHODS: Subjects were from the Duke Established Populations for the Epidemiologic Study of the Elderly, selected on the basis of stratified random household sampling. Blacks were oversampled to allow for increased statistical precision in racial comparisons. In all, 1,732 subjects (aged > 70 years) consented to blood drawing and constitute the sample for this study. Monoclonal immunoglobulins were determined by agarose gel electrophoresis and immunofixation. RESULTS: One hundred six subjects (6.1%) had a monoclonal gammopathy. There was a greater than twofold difference in prevalence between blacks (8.4%) and whites (3.8%) (P < 0.001); monoclonal gammopathy prevalence increased with age, and was greater in men than women. Those with monoclonal gammopathy did not differ from those without in socioeconomic status, urban/rural residence, or education. The presence of monoclonal gammopathy was not associated with any specific diseases nor with impaired functional status. There was a slight increase in serum creatinine levels and decrease in hemoglobin and albumin levels in patients with monoclonal gammopathy, but no difference in interleukin-6 (IL-6) levels. Moreover, IL-6 levels were not correlated significantly with the level of monoclonal protein. CONCLUSION: Prevalence of monoclonal gammopathy is significantly greater among blacks than whites in a community-based sample, in approximately the same ratio that multiple myeloma has been reported in the two groups. Given the absence of correlation with environmental factors, there may be a biological racial difference in susceptibility to an early event in the carcinogenic process leading to multiple myeloma.

Authors
Cohen, HJ; Crawford, J; Rao, MK; Pieper, CF; Currie, MS
MLA Citation
Cohen, HJ, Crawford, J, Rao, MK, Pieper, CF, and Currie, MS. "Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly." Am J Med 104.5 (May 1998): 439-444.
PMID
9626026
Source
pubmed
Published In
The American Journal of Medicine
Volume
104
Issue
5
Publish Date
1998
Start Page
439
End Page
444

Erratum: Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly (The American Journal of Medicine (1998) 104 (439-444))

Authors
Cohen, HJ; Crawford, J; Rao, MK
MLA Citation
Cohen, HJ, Crawford, J, and Rao, MK. "Erratum: Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly (The American Journal of Medicine (1998) 104 (439-444))." American Journal of Medicine 105.4 (1998): 362--.
Source
scival
Published In
American Journal of Medicine
Volume
105
Issue
4
Publish Date
1998
Start Page
362-

Erythropoietin and the management of anemia in patients with lung cancer

The onset of anemia is a confounding factor that will affect the majority of patients with lung cancer. In an attempt to manage or prevent anemia in this population, three trials have incorporated erythropoietin in the treatment schedules. The results of erythropoietin use for cancer patients with anemia have been encouraging.

Authors
Crawford, J; Blackwell, S
MLA Citation
Crawford, J, and Blackwell, S. "Erythropoietin and the management of anemia in patients with lung cancer." Cancer Control 5.2 SUPPL. (1998): 26-32.
Source
scival
Published In
Cancer control : journal of the Moffitt Cancer Center
Volume
5
Issue
2 SUPPL.
Publish Date
1998
Start Page
26
End Page
32

Irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer

During the 1980s, platinum-based regimens were yielding response rates typically less than 25%, median survival durations of about 25 weeks, and 1- year survival rates less than 25% in patients with advanced nonsmall-cell lung cancer (NSCLC). Currently, results from single institution phase II trials of agents introduced in the 1990s show a doubling of these numbers, and results from multiinstitutional trials are demonstrating response rates ranging from 30% to 40%, median survival durations of 40 weeks, and 1 year survivals of 40%. Single agent irinotecan shows significant activity against NSCLC in preclinical and early phase I/II clinical studies, with activity similar to that for other new agents. Therapeutic synergy is observed in preclinical tumor models when irinotecan and cisplatin are combined, and phase I/II trials of this combination have demonstrated response rates ≥ 50%. Herein the author provides an overview of data from phase II trials of irinotecan and focuses on preliminary results of a large US multicenter phase II trial of weekly irinotecan plus monthly cisplatin in 52 patients with advanced NSCLC. A response rate of 28.9% (95% CI, 16.5%-41.2%) and a median survival of 9.9 months were observed in this trial. US studies to design a more optimal irinotecan/cisplatin regimen in the same patient population are ongoing, and early results are encouraging.

Authors
III, RD; Johnson, D; Crawford, J; Dimery, I; Eckardt, J; Eckhardt, SG
MLA Citation
III, RD, Johnson, D, Crawford, J, Dimery, I, Eckardt, J, and Eckhardt, SG. "Irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer." ONCOLOGY 12.8 SUPPL. (1998): 79-83.
PMID
9726097
Source
scival
Published In
Oncology
Volume
12
Issue
8 SUPPL.
Publish Date
1998
Start Page
79
End Page
83

The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy.

BACKGROUND: A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim (r-metHuG-CSF) on hematologic recovery following chemotherapy. PATIENTS AND METHODS: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment. Chemotherapy was delivered on days 1-3 of each 21-day cycle with Filgrastim initiated at 5 micrograms/kg/day subcutaneously (SC) beginning on day 4, day 6, or day 8 and continuing until post-nadir neutrophil recovery. RESULTS: During the first cycle of chemotherapy, the duration of neutropenia was similar for all three schedules; however, the pattern of absolute neutrophil count (ANC) recovery differed. In subsequent cycles of treatment, an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy. By contrast, patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one. Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment. CONCLUSION: Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery. Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6. Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery. Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered.

Authors
Crawford, J; Kreisman, H; Garewal, H; Jones, SE; Shoemaker, D; Pupa, MR; Armstrong, S; Tomita, D; Dziem, G
MLA Citation
Crawford, J, Kreisman, H, Garewal, H, Jones, SE, Shoemaker, D, Pupa, MR, Armstrong, S, Tomita, D, and Dziem, G. "The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy." Ann Oncol 8.11 (November 1997): 1117-1124.
PMID
9426331
Source
pubmed
Published In
Annals of Oncology
Volume
8
Issue
11
Publish Date
1997
Start Page
1117
End Page
1124

Safety of concomitant use of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor with cytotoxic chemotherapy agents.

Most studies that use recombinant granulocytopoietic cytokines, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), with the intent of attenuating neutropenia generally have delayed the administration of the cytokine until 24 to 72 hours following completion of chemotherapy. This practice was initiated out of theoretic concern that colony-stimulating factor administration may cycle and differentiate a population of normal cells, thus increasing their susceptibility to cycle-specific antineoplastic agents. The theory, in fact, has been substantiated by evidence from several clinical trials of concurrent administration. Thus, simultaneous administration of chemotherapy and G-CSF or GM-CSF should be limited to investigational protocols with scientific objectives, such as cycle compression or malignant cell sensitization.

Authors
Petros, WP; Crawford, J
MLA Citation
Petros, WP, and Crawford, J. "Safety of concomitant use of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor with cytotoxic chemotherapy agents." Curr Opin Hematol 4.3 (May 1997): 213-216. (Review)
PMID
9209839
Source
pubmed
Published In
Current Opinion in Hematology
Volume
4
Issue
3
Publish Date
1997
Start Page
213
End Page
216

Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832).

The maximum tolerated dose (MTD) of etoposide and carboplatin without growth factor support was previously defined by Cancer and Leukemia Group B (CALGB) as 200 and 125 mg/m2/day x 3, respectively, given every 28 days to previously untreated patients who have extensive, small-cell lung cancer (SCLC). Myelosuppression was dose-limiting. The purpose of this phase I trial was to determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support allows the dosage of the combination of etoposide and carboplatin to be increased above the previously determined MTD. In this CALGB study of 44 evaluable patients with performance status 0-2, cohorts were treated with etoposide and carboplatin given intravenously on days 1-3 followed by GM-CSF (molgramostim) given subcutaneously on days 4-18. Four dose levels of bacteria-derived recombinant GM-CSF (5, 10, 20 microg/kg/day and 5 microg/kg every 12 h), three dose levels of etoposide (200, 250, and 300 mg/m2/day x 3), and two dose levels of carboplatin (125 and 150 mg/m2/day x 3) were evaluated. There was no chemotherapy dose escalation in individual patients. With 5 microg/kg/d GM-CSF, the first etoposide and carboplatin cycle of 300 and 150 mg/m2/day x 3, respectively, could be administered with acceptable toxicity. However, GM-CSF did not allow repeated administration of this dose-escalated regimen every 21 days, since delayed platelet and/or neutrophil recovery was dose limiting in later cycles. These results demonstrate that GM-CSF alone has limited capability to support the repeated administration of high doses of etoposide and carboplatin. CALGB currently is testing the ability of interleukin (IL)-6 given with GM-CSF to ameliorate the cumulative myelosuppression of this intense regimen.

Authors
Luikart, SD; Herndon, JE; Hollis, DR; MacDonald, M; Maurer, LH; Crawford, J; Clamon, GH; Wright, J; Perry, MC; Ozer, H; Green, MR
MLA Citation
Luikart, SD, Herndon, JE, Hollis, DR, MacDonald, M, Maurer, LH, Crawford, J, Clamon, GH, Wright, J, Perry, MC, Ozer, H, and Green, MR. "Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832)." Am J Clin Oncol 20.1 (February 1997): 24-30.
PMID
9020283
Source
pubmed
Published In
American Journal of Clinical Oncology: Cancer Clinical Trials
Volume
20
Issue
1
Publish Date
1997
Start Page
24
End Page
30

A phase II study evaluating the efficacy of carboplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in patients with stage IIIB and IV non-small cell lung cancer and extensive small cell lung cancer.

We initiated a phase II pilot study to determine whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to combination carboplatin/etoposide is tolerable and active in patients with advanced non-small cell lung cancer and extensive small cell lung cancer. Patients were given carboplatin (area under the concentration-time curve of 6) followed by etoposide 80 to 100 mg/m2 intravenously on days 1 through 3 followed by paclitaxel 200 mg/m2 intravenously over 3 hours on day 3. On days 4 through 18, granulocyte colony-stimulating factor 5 microg/kg was administered subcutaneously. Each cycle was repeated every 21 days. Fourteen patients have been accrued to the study and 12 were evaluated for toxicity, the first 10 of whom were treated with 80 mg/m2 etoposide. Among the first 10 evaluable patients, significant grade 4 neutropenia occurred in one patient, grade 4 thrombocytopenia in three patients, grade 2 neuropathy in two patients, and grade 3 neurotoxicity in two patients. None of the four patients with non-small cell lung cancer responded to treatment, while six of seven small cell lung cancer patients have obtained major responses to therapy. We have increased the etoposide dose to 100 mg/m2 in subsequent patients. The combination chemotherapy regimen of carboplatin, etoposide, and paclitaxel is tolerable and active in patients with small cell lung cancer.

Authors
Neill, HB; Miller, AA; Clamon, GH; Perry, MC; Crawford, J; Green, MR
MLA Citation
Neill, HB, Miller, AA, Clamon, GH, Perry, MC, Crawford, J, and Green, MR. "A phase II study evaluating the efficacy of carboplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in patients with stage IIIB and IV non-small cell lung cancer and extensive small cell lung cancer." Seminars in oncology 24.4 Suppl 12 (1997): S12-130-S12-130134-.
PMID
9331137
Source
scival
Published In
Seminars in Oncology
Volume
24
Issue
4 Suppl 12
Publish Date
1997
Start Page
S12-130-S12-130134

Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer

Background: Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF, also known as PEG- rHuMGDF), a recombinant molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and platelet production and reduces the severity of thrombocytopenia in animals receiving myelosuppressive chemotherapy. Methods: We conducted a randomized, double-blind, placebo-controlled dose- escalation study of MGDF in 53 patients with lung cancer who were treated with carboplatin and paclitaxel. The patients were randomly assigned in blocks of 4 in a 1:3 ratio to receive either placebo or MGDF (0.03, 0.1, 0.3, 1.0, 3.0, or 5.0 μg per kilogram of body weight per day), injected subcutaneously. No other marrow-active cytokines were given. Results: In the 38 patients who received MGDF after chemotherapy, the median nadir platelet count was 188,000 per cubic millimeter (range, 68,000 to 373,000), as compared with 111,000 per cubic millimeter (range, 21,000 to 307,000) in 12 patients receiving placebo (P = 0.013). The platelet count recovered to base- line levels in 14 days in the treated patients as compared with more than 21 days in those receiving placebo (P<0.001). Among all 40 patients treated with MGDF, 1 had deep venous thrombosis and pulmonary embolism, and another had superficial thrombophlebitis. Conclusions: MGDF has potent stimulatory effects on platelet production in patients with chemotherapy-induced thrombocytopenia.

Authors
Fanucchi, M; Glaspy, J; Crawford, J; Garst, J; Figlin, R; Sheridan, W; Menchaca, D; Tomita, D; Ozer, H; Harker, L
MLA Citation
Fanucchi, M, Glaspy, J, Crawford, J, Garst, J, Figlin, R, Sheridan, W, Menchaca, D, Tomita, D, Ozer, H, and Harker, L. "Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer." New England Journal of Medicine 336.6 (1997): 404-409.
PMID
9010146
Source
scival
Published In
The New England journal of medicine
Volume
336
Issue
6
Publish Date
1997
Start Page
404
End Page
409
DOI
10.1056/NEJM199702063360603

Docetaxel/vinorelbine combination therapy in non-small-cell lung cancer

Docetaxel (Taxotere) has demonstrated significant activity as a single agent in the treatment of patients with advanced non-small-cell lung cancer. Projected median survival in both previously untreated and treated patients is reported to be 9 months. In addition, response rates have ranged from 33% to 38% and 21% to 27% in these respective patient populations. Because vinorelbine (Navelbine) has been demonstrated to have a survival benefit in randomized trials in patients with non-small-cell lung cancer, the potential for the combined use of these agents is promising. In addition, the side effect profiles of docetaxel and vinorelbine are compatible for the combined use of these agents in patients with advanced non-small-cell lung cancer. Preliminary results from phase I and II combination studies have shown encouraging results, with partial responses ranging from 23% to 55%. Based on these data, further study into the combined use of docetaxel and vinorelbine in patients with non-small-cell lung cancer is warranted.

Authors
Crawford, J
MLA Citation
Crawford, J. "Docetaxel/vinorelbine combination therapy in non-small-cell lung cancer." ONCOLOGY 11.7 SUPPL. (1997): 35-40.
Source
scival
Published In
Oncology
Volume
11
Issue
7 SUPPL.
Publish Date
1997
Start Page
35
End Page
40

Vinorelbine and carboplatin in the treatment of advanced non-small-cell lung cancer

Randomized trials in patients with advanced non-small-cell lung cancer (NSCLC) have demonstrated that the combination of vinorelbine (Navelbine) and cisplatin (Platinol), compared with vinorelbine alone, increases survival but also increases toxicity. In an effort to enhance survival and reduce toxicity, a phase I/II trial of vinorelbine and carboplatin was conducted. On the basis of the phase I experience in 22 patients, the regimen chosen for evaluation in phase II consisted of vinorelbine 30 mg/m2/week, carboplatin at an area under the concentration vs time curve of 7 (according to the Calvert formula) on a monthly basis, and granulocyte colony-stimulating factor (G-CSF) titrated according to the absolute neutrophil count. As in phase I, neutropenia was the major toxicity observed among the 42 patients in the phase II study. However, the use of G-CSF either in a reactive setting (after the development of neutropenia) or preemptively (prior to the development of neutropenia) limited the episodes of febrile neutropenia. The overall 1-year survival rate was comparable to results obtained with vinorelbine and cisplatin in large-scale trials, with a favorable toxicity profile. These results confirm the clinical activity of vinorelbine plus carboplatin in advanced non-small-cell lung cancer.

Authors
Crawford, J; Garst, J; O'Rourke, MA
MLA Citation
Crawford, J, Garst, J, and O'Rourke, MA. "Vinorelbine and carboplatin in the treatment of advanced non-small-cell lung cancer." ONCOLOGY 11.10 SUPPL. 12 (1997): 44-48.
Source
scival
Published In
ONCOLOGY
Volume
11
Issue
10 SUPPL. 12
Publish Date
1997
Start Page
44
End Page
48

A phase II study evaluating the efficacy of carboplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in patients with stage IIIB and IV non-small cell lung cancer and extensive small cell lung cancer

We initiated a phase II pilot study to determine whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to combination carboplatin/etoposide is tolerable and active in patients with advanced non-small cell lung cancer and extensive small cell lung cancer. Patients were given carboplatin (area under the concentration-time curve of 6) followed by etoposide 80 to 100 mg/m2 intravenously on days 1 through 3 followed by paclitaxel 200 mg/m2 intravenously over 3 hours on day 3. On days 4 through 18, granulocyte colony-stimulating factor 5 μg/kg was administered subcutaneously. Each cycle was repeated every 21 days. Fourteen patients have been accrued to the study and 12 were evaluated for toxicity, the first 10 of whom were treated with 80 mg/m2 etoposide. Among the first 10 evaluable patients, significant grade 4 neutropenia occurred in one patient, grade 4 thrombocytopenia in three patients, grade 2 neuropathy in two patients, and grade 3 neurotoxicity in two patients. None of the four patients with non-small cell lung cancer responded to treatment, while six of seven small cell lung cancer patients have obtained major responses to therapy. We have increased the etoposide dose to 100 mg/m2 in subsequent patients. The combination chemotherapy regimen of carboplatin, etoposide, and paclitaxel is tolerable and active in patients which small cell lung cancer.

Authors
Niell, HB; Miller, AA; Clamon, GH; Perry, MC; Crawford, J; Green, MR
MLA Citation
Niell, HB, Miller, AA, Clamon, GH, Perry, MC, Crawford, J, and Green, MR. "A phase II study evaluating the efficacy of carboplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in patients with stage IIIB and IV non-small cell lung cancer and extensive small cell lung cancer." Seminars in Oncology 24.4 SUPPL.12 (1997): S12130-S12134.
Source
scival
Published In
Seminars in Oncology
Volume
24
Issue
4 SUPPL.12
Publish Date
1997
Start Page
S12130
End Page
S12134

Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer.

PURPOSE: This prospective randomized trial was performed to compare the effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil and leucovorin (5-FU/LV) on the primary end points of survival, quality of life (QOL), and relief of cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). Secondary end points included tumor response rates and time to treatment failure. In addition, the safety of both treatment regimens was evaluated in this multicenter study. PATIENTS AND METHODS: Two hundred sixteen patients with stage IV NSCLC were enrolled onto this study from 18 centers. Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4 weeks. Patients with progressive disease or toxicity were removed from study while responding and stable patients were continued on therapy. RESULTS: The median survival time of patients who received vinorelbine was 30 weeks, with 25% of patients alive at 1 year, compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank test). This improvement in survival was associated with a higher objective response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia. Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most common grade 3 toxicities were related to injection-site reactions. CONCLUSION: This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC. The clinical activity and relatively favorable toxicity profile of this agent make it a reasonable and useful treatment option in the management of patients with this disease.

Authors
Crawford, J; O'Rourke, M; Schiller, JH; Spiridonidis, CH; Yanovich, S; Ozer, H; Langleben, A; Hutchins, L; Koletsky, A; Clamon, G; Burman, S; White, R; Hohneker, J
MLA Citation
Crawford, J, O'Rourke, M, Schiller, JH, Spiridonidis, CH, Yanovich, S, Ozer, H, Langleben, A, Hutchins, L, Koletsky, A, Clamon, G, Burman, S, White, R, and Hohneker, J. "Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer." J Clin Oncol 14.10 (October 1996): 2774-2784.
PMID
8874339
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
14
Issue
10
Publish Date
1996
Start Page
2774
End Page
2784
DOI
10.1200/JCO.1996.14.10.2774

A randomized phase II study of ifosfamide/mesna/cisplatin plus G-CSF or etoposide/cisplatin plus G-CSF in advanced non-small cell lung cancer: a Cancer and Leukemia Group B study.

This Phase II study was designed to determine the efficacy of two chemotherapy regimens with G-CSF support for patients with advanced non-small cell lung cancer (NSCLC). One-hundred and one patients with Stage IIIB or IV NSCLC and performance status 0-1 were randomized to receive ifosfamide 2.0 g/m2 days 1-3, mesna 400 mg/m2 at 0, 4, 6 h days 1-3, cisplatin 33 mg/m2 days 1-3 or etoposide 200 mg/m2 days 1-3, cisplatin 35 mg/m2 days 1-3. Both groups received G-CSF 5 micrograms/kg SQ day 4 to the post day 11 absolute neutrophil count > 10 000. For the 47 eligible patients receiving ifosfamide/mesna/cisplatin, the response rate was 26% (95% confidence interval: 14-40%) and the median survival 7.5 months (95% confidence interval: 5.8-11.0 months). Grade 3 or worse toxicities were: neutropenia 75%, thrombocytopenia 70%, infection 21%. There were two treatment-related deaths due to infection. For course 1, the median absolute neutrophil count nadir was 1.3, platelet nadir 96 000 and incidence of febrile neutropenia 16%. For the 48 eligible patients receiving etoposide/cisplatin, the response rate was 21% (95% confidence interval: 11-35%) and median survival 5.8 months (95% confidence interval: 4.5-9.7 months). Grade 3 or worse toxicities were: neutropenia 90%, thrombocytopenia 58%, infection 29%. There were three treatment-related deaths due to infection. For course 1, the median absolute neutrophil count was 0.2, platelet nadir 80 000 and incidence of febrile neutropenia 33%. For both ifosfamide/mesna/cisplatin and etoposide/cisplatin, median duration of Grade IV neutropenia was short (< or = 4 days), time to subsequent courses 21 days and dose delivered > 95% of planned dose. Although G-CSF allowed full doses of drugs to be delivered on schedule, both ifosfamide/mesna/cisplatin and etoposide/cisplatin produced response rates and survival similar to other cisplatin-based regimens. In view of the significant cost of G-CSF and no obvious improvement in response rate, survival or toxicity profile, G-CSF cannot be recommended with these chemotherapy regimens for patients with advanced NSCLC.

Authors
Graziano, SL; Valone, FH; Herndon, JE; Crawford, J; Richards, F; Rege, VB; Clamon, G; Green, MR
MLA Citation
Graziano, SL, Valone, FH, Herndon, JE, Crawford, J, Richards, F, Rege, VB, Clamon, G, and Green, MR. "A randomized phase II study of ifosfamide/mesna/cisplatin plus G-CSF or etoposide/cisplatin plus G-CSF in advanced non-small cell lung cancer: a Cancer and Leukemia Group B study." Lung Cancer 14.2-3 (June 1996): 315-329.
PMID
8794413
Source
pubmed
Published In
Lung Cancer
Volume
14
Issue
2-3
Publish Date
1996
Start Page
315
End Page
329

Ambulatory sclerotherapy for malignant pleural effusions.

PURPOSE: To determine the feasibility of ambulatory drainage and sclerotherapy in malignant pleural effusions. MATERIALS AND METHODS: Nineteen consecutive patients with symptomatic malignant pleural effusions were enrolled. None of the patients previously underwent sclerotherapy. A fluoroscopically placed 10.3-F catheter was connected to a closed gravity drainage bag system. Sclerotherapy was performed with bleomycin when daily drainage was less than 100 mL. Radiographic response was graded at 30 days. All patients were examined for symptomatic response and for complications. RESULTS: The tubes remained in place 2-11 days (mean, 5.1 days). Total pleural drainage ranged from 950 to 3,925 mL (mean, 1,647 mL); all 19 patients had improvement of symptoms. At 30 days, 10 (53%) patients had a complete response, five (26%) had a partial response, and four (21%) had progressive disease. CONCLUSION: Ambulatory sclerotherapy is a safe, viable alternative to conventional inpatient treatment of malignant pleural effusions.

Authors
Patz, EF; McAdams, HP; Goodman, PC; Blackwell, S; Crawford, J
MLA Citation
Patz, EF, McAdams, HP, Goodman, PC, Blackwell, S, and Crawford, J. "Ambulatory sclerotherapy for malignant pleural effusions." Radiology 199.1 (April 1996): 133-135.
PMID
8633136
Source
pubmed
Published In
Radiology
Volume
199
Issue
1
Publish Date
1996
Start Page
133
End Page
135
DOI
10.1148/radiology.199.1.8633136

Update of recommendations for the use of hematopoietic colony-stimulating factors: Evidence-based clinical practice guidelines

Authors
Smith, TJ; Ozer, H; Miller, LL; Schiffer, CA; Winn, RJ; Anderson, JR; Anderson, PN; Armitage, JO; Beckhardt, S; Bennett, CL; Bodey, GP; Crawford, J; Davidson, NE; Demetri, GD; Hamm, JT; Hillner, B; Kardinal, CG; Levine, MN; Miller, JA; Ochs, JJ; Santana, VM; Shea, TC; Vadhan-Raj, S; III, JLW; Weeks, JC
MLA Citation
Smith, TJ, Ozer, H, Miller, LL, Schiffer, CA, Winn, RJ, Anderson, JR, Anderson, PN, Armitage, JO, Beckhardt, S, Bennett, CL, Bodey, GP, Crawford, J, Davidson, NE, Demetri, GD, Hamm, JT, Hillner, B, Kardinal, CG, Levine, MN, Miller, JA, Ochs, JJ, Santana, VM, Shea, TC, Vadhan-Raj, S, III, JLW, and Weeks, JC. "Update of recommendations for the use of hematopoietic colony-stimulating factors: Evidence-based clinical practice guidelines." Journal of Clinical Oncology 14.6 (1996): 1957-1960.
PMID
8656266
Source
scival
Published In
Journal of Clinical Oncology
Volume
14
Issue
6
Publish Date
1996
Start Page
1957
End Page
1960

Combination regimens and dose intensification in non-small cell lung cancer: A panel discussion (Part I)

Authors
Crawford, J; Chang, AY; Gralla, RJ; Souquet, PJ; Vokes, EE
MLA Citation
Crawford, J, Chang, AY, Gralla, RJ, Souquet, PJ, and Vokes, EE. "Combination regimens and dose intensification in non-small cell lung cancer: A panel discussion (Part I)." Seminars in Oncology 23.2 SUPPL. 5 (1996): 22-24.
PMID
8610233
Source
scival
Published In
Seminars in Oncology
Volume
23
Issue
2 SUPPL. 5
Publish Date
1996
Start Page
22
End Page
24

Update on the role of vinorelbine in the treatment of non-small cell lung cancer: Introduction

Authors
Crawford, J; Vokes, EE
MLA Citation
Crawford, J, and Vokes, EE. "Update on the role of vinorelbine in the treatment of non-small cell lung cancer: Introduction." Seminars in Oncology 23.2 SUPPL. 5 (1996): 1--.
Source
scival
Published In
Seminars in Oncology
Volume
23
Issue
2 SUPPL. 5
Publish Date
1996
Start Page
1-

Pharmacoeconomics, quality of life, and combination modalities in non- small cell lung cancer: A panel discussion (Part 2)

Authors
Crawford, J; Duch, DS; Gralla, RJ; Hillner, BE; Hollen, PJ; Vokes, EE
MLA Citation
Crawford, J, Duch, DS, Gralla, RJ, Hillner, BE, Hollen, PJ, and Vokes, EE. "Pharmacoeconomics, quality of life, and combination modalities in non- small cell lung cancer: A panel discussion (Part 2)." Seminars in Oncology 23.2 SUPPL. 5 (1996): 53-55.
PMID
8610238
Source
scival
Published In
Seminars in Oncology
Volume
23
Issue
2 SUPPL. 5
Publish Date
1996
Start Page
53
End Page
55

Update: Vinorelbine (Navelbine) in non-small cell lung cancer

Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France), a novel semisynthetic vinca alkaloid, is the first drug approved by the Food and Drug Administration in over 20 years for the first-line treatment of ambulatory patients with unresectable advanced non-small cell lung cancer (NSCLC). In a multicenter, randomized US trial, single-agent vinorelbine produced response rates of 12%, compared with prior single-center studies demonstrating a response rate of 30%. Furthermore, in the US trial, median survival for patients receiving vinorelbine was 30 weeks, with a 1-year survival rate of 25%, compared with 22 weeks for S-fluorouracil and leucovorin, with a 1-year survival rate of 16%. This impact on survival was confirmed in a European multicenter randomized trial. In this study, vinorelbine as a single agent demonstrated a median survival of 31 weeks, with a 1-year survival rate of 30%. Single- agent vinorelbine was comparable to the combination of vindesine/cisplatin, which had a median survival of 32 weeks and a 1-year survival rate of 27%. By contrast, the combination of vinorelbine/cisplatin produced a medial survival of 40 weeks and a 1-year survival rate of 35%. The major dose-limiting toxic effect of vinorelbine is granulocytopenia. Vinorelbine has demonstrated a survival advantage in patients with advanced NSCLC in two controlled clinical trials and has been associated with a favorable safety profile associated with a low incidence of hospitalization. These findings would suggest that vinorelbine alone or in combination with cisplatin may be a cost-effective treatment for appropriate patients with advanced NSCLC.

Authors
Crawford, J
MLA Citation
Crawford, J. "Update: Vinorelbine (Navelbine) in non-small cell lung cancer." Seminars in Oncology 23.2 SUPPL. 5 (1996): 2-7.
PMID
8610232
Source
scival
Published In
Seminars in Oncology
Volume
23
Issue
2 SUPPL. 5
Publish Date
1996
Start Page
2
End Page
7

Human recombinant stem-cell factor induces melanocytic hyperplasia in susceptible patients.

BACKGROUND: Recombinant human stem-cell factor (SCF), a cytokine acting on hematopoietic progenitor cells, has potential for the treatment of several hematologic and oncologic disorders. In a hematology-oncology phase I trial of SCF, several patients had cutaneous hyperpigmentation at the SCF subcutaneous injection sites. OBJECTIVE: Our purpose was to investigate the pathogenesis of this hyperpigmentation phenomenon. METHODS: Skin biopsy specimens were obtained before, at the completion of, and after SCF therapy and were processed for histology, immunohistology, and electron microscopy. RESULTS: Skin at the site of SCF injection had an increased number of melanocytes, increased melanocytic dendrite extension, and melanin as compared with noninjected tissue. Immunohistochemical stains revealed an increase in staining with melanocyte-specific monoclonal antibodies HMB-45 and NKI/beteb, and a monoclonal antibody to the receptor for SCF, c-kit. CONCLUSION: Subcutaneous injection of SCF results in hyperplasia of melanocytes. SCF may be useful in the treatment of melanocytopenic disorders, but caution may be necessary in patients with disorders of melanocyte proliferation.

Authors
Grichnik, JM; Crawford, J; Jimenez, F; Kurtzberg, J; Buchanan, M; Blackwell, S; Clark, RE; Hitchcock, MG
MLA Citation
Grichnik, JM, Crawford, J, Jimenez, F, Kurtzberg, J, Buchanan, M, Blackwell, S, Clark, RE, and Hitchcock, MG. "Human recombinant stem-cell factor induces melanocytic hyperplasia in susceptible patients." J Am Acad Dermatol 33.4 (October 1995): 577-583.
PMID
7545704
Source
pubmed
Published In
Journal of The American Academy of Dermatology
Volume
33
Issue
4
Publish Date
1995
Start Page
577
End Page
583

The role of hematopoietic growth factors in support of ifosfamide/carboplatin/etoposide chemotherapy

The ifosfamide/carboplatin/etoposide (ICE) combination represents an active chemotherapy regimen across a wide variety of disease types. The most common limiting toxicity for all three of these agents individually and in combination is myelosuppression. Thus, this regimen represents an ideal model to evaluate the role of hematopoietic growth factor support in amelioration of hematologic toxicity, maintenance of dose intensity, and dose escalation. While chemotherapy strategies using colony-stimulating factors have abrogated neutropenia, cumulative thrombocytopenia is common with many chemotherapy regimens, including ICE chemotherapy. In preclinical and phase II trials, monotherapy with recombinant human interleukin-6 (IL-6) has demonstrated substantial thrombopoietic activity, but with little enhancement of neutrophil recovery. Thus, this study was designed to evaluate combination cytokine therapy with both recombinant IL-6 and granulocyte colony- stimulating factor (G-CSF) after ICE chemotherapy. Previously untreated patients with inoperable non-small cell lung cancer are eligible. Treatment includes two monthly cycles of ifosfamide 2,000 mg/m2 with mesna 1,600 mg/m2 intravenously on days 1, 2, and 3, carboplatin 350 mg/m2 intravenously on day 1 only, and etoposide 75 mg/m2 intravenously on days 1, 2, and 3. All patients then receive G-CSF at a dose of 5 μg/kg/d subcutaneously beginning on day 4 until a postnadir absolute neutrophil count of more than 10 x 109/L. Cohorts of patients (n = 15) are randomized to receive 0, 1, 2.5, or 5 μg/kg/d of IL-6 subcutaneously on days 4 to 13 in successive cohorts. This study has now reached its target accrual in all cohorts. The final data analysis is in progress. It is hoped that this trial will define the safety and tolerability of the simultaneous administration of IL-6 and G-CSF following ICE chemotherapy in patients with non-small cell lung cancer. In addition, this trial should determine the biologic activity and hematopoietic recovery observed during the simultaneous administration of these two cytokines in this setting.

Authors
Crawford, J; George, M
MLA Citation
Crawford, J, and George, M. "The role of hematopoietic growth factors in support of ifosfamide/carboplatin/etoposide chemotherapy." Seminars in Oncology 22.3 SUPPL. 7 (1995): 18-22.
PMID
7541916
Source
scival
Published In
Seminars in Oncology
Volume
22
Issue
3 SUPPL. 7
Publish Date
1995
Start Page
18
End Page
22

Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non-small cell lung cancer.

BACKGROUND: The purpose of this study was to assess the ability of administering to patients induction chemotherapy with carboplatin and etoposide (VP-16), followed by full-course radiation therapy and weekly carboplatin with tolerable toxicity as preoperative therapy to down-stage disease thus allowing the resection of clinically staged IIIA non-small cell lung cancer. METHODS: Twenty-eight eligible patients with good performance status and previously untreated, marginally resectable stage IIIA non-small cell lung cancer received induction chemotherapy with carboplatin (dosed per the Egorin formulation), and VP-16 (100 mg/m2) followed by 6000 cGy of chest radiotherapy over six weeks administered concurrently with weekly doses of 100 mg/m2 of carboplatin. Patients who had either responsive or stable disease underwent thoracotomy, with attempted surgical resection of the primary lung lesion and the areas of abnormal adenopathy. Procedures involving less than a pneumonectomy were used whenever feasible. RESULTS: Fifty-two cycles of induction chemotherapy were administered. The average initial dose of carboplatin was 407 mg/m2. Toxicity was tolerable with grade 3-4 neutropenia and/or thrombocytopenia in 48 and 27% of the patients. There were no septic deaths. Full-dose radiotherapy was administered to 82% of patients, with 73% receiving at least five weekly doses of carboplatin. The radiographically assessed response rate to the neoadjuvant treatment was 64% (partial response, 46%; minimal response, 18%). Sixteen patients underwent gross tumor resection with 12 (43%) having negative pathologic margins. Six patients had pneumonectomy. There were three perioperative deaths (19%); two were secondary to respiratory failure after the patients underwent a pneumonectomy. The median survival for all 28 patients was 15 months, and for the 16 patients undergoing thoracotomy was 23 months. Eight patients were alive and in remission, with follow-up ranging from 8 to 31 months. CONCLUSIONS: The authors conclude that (1) carboplatin and VP-16, followed by full-dose radiotherapy with weekly carboplatin administration, is a well tolerated and effective regimen in the treatment of patients with marginally resectable stage IIIA non-small cell lung cancer; and (2) full-course radiotherapy can be administered before surgical resection without additional surgical morbidity or mortality.

Authors
Deutsch, M; Crawford, J; Leopold, K; Wolfe, W; Foster, W; Herndon, J; Blackwell, S; Yost, R
MLA Citation
Deutsch, M, Crawford, J, Leopold, K, Wolfe, W, Foster, W, Herndon, J, Blackwell, S, and Yost, R. "Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non-small cell lung cancer." Cancer 74.4 (August 15, 1994): 1243-1252.
PMID
8055445
Source
pubmed
Published In
Cancer
Volume
74
Issue
4
Publish Date
1994
Start Page
1243
End Page
1252

A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease.

BACKGROUND: Advanced stage Hodgkin's disease (HD) usually is treated with combination chemotherapy with or without supplemental irradiation. The risk of significant acute and long term toxicity when the chemotherapy regimen contains alkylating agents has provided the impetus for the development of systemic combinations that do not include alkylating agents. This trial was designed to assess the toxicity and efficacy of a regimen of etoposide, vinblastine, and doxorubicin (EVA) as part of a combined modality approach in patients with moderate to high risk HD. METHODS: This was a prospective pilot study that included 26 previously untreated patients. They received 6 cycles of EVA, and complete responders received low dose (1500-2500 cGy) involved field radiation. RESULTS: Four patients were hospitalized for sepsis during chemotherapy. Complete response was achieved in 54% of patients, and 46% patients experienced induction failures. Two year failure-free survival is 44%, while 2 year overall survival is 86%. Median follow-up is 27 months. CONCLUSIONS: The EVA regimen is no more efficacious than other programs already in use and may be less so. It also is potentially leukemogenic because of the presence of etoposide. New combinations that do not contain etoposide should be explored in therapy programs for advanced HD in the hopes of discovering an efficacious treatment program that has minimal long term side effects.

Authors
Brizel, DM; Gockerman, JP; Crawford, J; Hathorn, JW; Moore, JO; Osborne, B; Prosnitz, LR
MLA Citation
Brizel, DM, Gockerman, JP, Crawford, J, Hathorn, JW, Moore, JO, Osborne, B, and Prosnitz, LR. "A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease." Cancer 74.1 (July 1, 1994): 159-163.
PMID
8004571
Source
pubmed
Published In
Cancer
Volume
74
Issue
1
Publish Date
1994
Start Page
159
End Page
163

Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer

Background. Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy- related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. Methods. Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, <1.0 x 109 per liter, with a temperature ≥38.2°C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. Results. The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P < 0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, <0.5 x 109 per liter) was six days with placebo as compared with one day with G- CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. Conclusions. The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.

Authors
Crawford, J; Ozer, H; Stoller, R; Johnson, D; Lyman, G; Tabbara, I; Kris, M; Grous, J; Picozzi, V; Rausch, G; Smith, R; Gradishar, W; Yahanda, A; Vincent, M; Stewart, M; Glaspy, J
MLA Citation
Crawford, J, Ozer, H, Stoller, R, Johnson, D, Lyman, G, Tabbara, I, Kris, M, Grous, J, Picozzi, V, Rausch, G, Smith, R, Gradishar, W, Yahanda, A, Vincent, M, Stewart, M, and Glaspy, J. "Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer." Clinical Infectious Diseases 18.SUPPL. 2 (1994): S189-S196.
Source
scival
Published In
Clinical Infectious Diseases
Volume
18
Issue
SUPPL. 2
Publish Date
1994
Start Page
S189
End Page
S196

Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies: Psychometric assessment of the lung cancer symptom scale

Background. This study continued the development and psychometric testing of the Lung Cancer Symptom Scale (LCSS), a disease- and site-specific instrument primarily measuring the physical and functional dimensions of quality of life for individuals with lung cancer. The instrument contains two scales, one for patients and a counterpart for health professionals as observers. Methods. Feasibility, reliability, construct validity, and criterion-related validity were evaluated with 207 patients with non-small cell lung cancer (NSCLC) from six cancer centers. Within an interview with an observer, patients completed part of a battery of instruments by self-report and were interviewed for the remaining measures. Observers also completed measures after the interview. Results. Feasibility, reliability, and validity were well supported for this lung cancer population. Feasibility was demonstrated by patient and staff compliance in completion at all six cancer centers. Internal consistency was good, with coefficient alphas of 0.82 for the patient scale and 0.75 for the observer scale. Construct validity was supported by: 1. contrasted groups approach: regression lines (with 95% confidence bands) were obtained between the Karnofsky performance scale (KPS) and each of the two LCSS scales; 2. as a refinement, relationship testing: significant correlations between the LCSS and KPS for each item (except hemoptysis for the patient scale); and 3. multitrait-multimethod approach: good reliability (alphas ranging from 0.75 to 0.93), good convergent validity for the two LCSS scales (r = 0.77), and a good discriminant validity pattern from the Brief Symptom Inventory (BSI). Criterion-related validity with relevant gold standard measures (American Thoracic Society Questionnaire [ATS] and McGill Pain questionnaire, KPS, Profiles of Mood States [POMS], and Sickness Impact Profile [SIP]) was supported with significant correlations (0.40-0.67 for the LCSS patient scale; 0.54-0.65 for the LCSS observer scale). Conclusions. These psychometric properties demonstrate that the LCSS patient and observer scales are feasible, reliable, and valid quality of life measures that are ready for research and clinical use with lung cancer populations.

Authors
Hollen, PJ; Gralla, RJ; Kris, MG; Cox, C; Belani, CP; Grunberg, SM; Crawford, J; Neidhart, JA
MLA Citation
Hollen, PJ, Gralla, RJ, Kris, MG, Cox, C, Belani, CP, Grunberg, SM, Crawford, J, and Neidhart, JA. "Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies: Psychometric assessment of the lung cancer symptom scale." Cancer 73.8 (1994): 2087-2098.
PMID
8156514
Source
scival
Published In
Cancer
Volume
73
Issue
8
Publish Date
1994
Start Page
2087
End Page
2098

Stem cell factor is a potent synergistic factor in hematopoiesis

Stem cell factor (SCF), a ligand for c-kit, has a broad range of activities including effects on cells at or near the level of the multipotential stem cell as well as on committed cells. Preclinical studies show that SCF can protect against lethal irradiation, elicit multilineage responses in peripheral blood and bone marrow cellularity, and increase circulating peripheral blood progenitor cells (PBPC) in a dose-dependent manner. Recombinant human SCF has major clinical potential through its synergy with other factors, especially recombinant human granulocyte colony-stimulating factor, to enhance mobilization of PBPC.

Authors
Morstyn, G; Brown, S; Gordon, M; Crawford, J; Demetri, G; Rich, W; McGuire, B; Foote, MA; McNiece, I
MLA Citation
Morstyn, G, Brown, S, Gordon, M, Crawford, J, Demetri, G, Rich, W, McGuire, B, Foote, MA, and McNiece, I. "Stem cell factor is a potent synergistic factor in hematopoiesis." Oncology 51.2 (1994): 205-214.
PMID
7515171
Source
scival
Published In
Oncology
Volume
51
Issue
2
Publish Date
1994
Start Page
205
End Page
214

Vinorelbine (Navelbine)/carboplatin combination therapy: Dose intensification with granulocyte colony-stimulating factor

Treatment with platinum agents or the new vinca alkaloid vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) results in prolonged survival in patients with advanced non-small cell lung cancer (NSCLC). To determine whether a unique combination of these agents might enhance activity against NSCLC, a combination chemotherapy regimen consisting of intravenous carboplatin, administered on days 1 and 29, and intravenous vinorelbine, given once weekly, was evaluated. Because the dose-limiting toxicity of both agents is myelosuppression, an additional study goal was to assess the ability of granulocyte colony-stimulating factor to alleviate hematologic toxicity and allow on-time, full-dose vinorelbine therapy. To this end, a phase I/II study was begun. Phase I of the study included 22 patients (15 men and seven women) with a median age of 63 years (age range, 39 to 77 years) who had stage IV NSCLC and no prior chemotherapy. Phase I consisted of 28-day cycles in which intravenous carboplatin was administered at an area under the curve of 7 by the Calvert formula, dose range 350 to 450 mg/m2, and intravenous vinorelbine was administered weekly. Granulocyte colony-stimulating factor was administered if dose-limiting neutropenia developed. Four cohorts of patients were studied, ranging from those who received no vinorelbine to those who received drug doses of up to 30 mg/m2. Patients were able to tolerate the highest dose of vinorelbine, but the majority required granulocyte colony-stimulating factor support to do so. No novel toxicities were observed in patients treated with the combination of carboplatin and vinorelbine. Both the response rate (29% in patients treated with both agents) and preliminary survival data suggest that this regimen holds promise for the treatment of patients with NSCLC.

Authors
Crawford, J; O'Rourke, MA; Coltman,
MLA Citation
Crawford, J, O'Rourke, MA, and Coltman, . "Vinorelbine (Navelbine)/carboplatin combination therapy: Dose intensification with granulocyte colony-stimulating factor." Seminars in Oncology 21.5 SUPPL. 10 (1994): 73-78.
PMID
7526467
Source
scival
Published In
Seminars in Oncology
Volume
21
Issue
5 SUPPL. 10
Publish Date
1994
Start Page
73
End Page
78

Vinorelbine (Navelbine) in non-small cell lung cancer: Future directions

Randomized clinical trials of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) as a single agent and in combination with cisplatin have demonstrated antitumor activity in patients with advanced non-small cell lung cancer (NSCLC). Administered as a single agent on a weekly schedule, the vinorelbine therapeutic profile compares favorably with other regimens currently used in palliative treatment of patients with advanced NSCLC. Vinorelbine is also being considered in other treatment settings as well: adjuvant treatment in stage I and II disease, and regimens with curative intent in stage IIIa and IIIb disease. Future directions for vinorelbine in the treatment of NSCLC are likely to be directed toward combination trials with other agents active in NSCLC. Current phase I-II trials, for example, combine vinorelbine with cisplatin, 5-fluorouracil/leucovorin, mitomycin-C, ifosfamide, carboplatin, and paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ). Some phase III trials are planned and some are under way. Vinorelbine has been a focus of interest in multimodality trials. A Canadian trial, for example, combined vinorelbine and cisplatin, followed by accelerated radiation. Results from all these trials can be expected to guide the further development of vinorelbine in adjuvant and neoadjuvant settings in NSCLC. Moreover, trials that are documenting the efficacy of vinorelbine in small cell lung cancer are just beginning.

Authors
Crawford, J
MLA Citation
Crawford, J. "Vinorelbine (Navelbine) in non-small cell lung cancer: Future directions." Seminars in Oncology 21.5 SUPPL. 10 (1994): 85-88.
PMID
7526468
Source
scival
Published In
Seminars in Oncology
Volume
21
Issue
5 SUPPL. 10
Publish Date
1994
Start Page
85
End Page
88

Lung cancer in North Carolina.

Authors
Rimer, BK; Herman, D; Crawford, J; Blackwell, S
MLA Citation
Rimer, BK, Herman, D, Crawford, J, and Blackwell, S. "Lung cancer in North Carolina." N C Med J 54.7 (July 1993): 334-340.
PMID
8394512
Source
pubmed
Published In
North Carolina Medical Journal
Volume
54
Issue
7
Publish Date
1993
Start Page
334
End Page
340

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered intravenously at a dose of 15 mg/m2 to 31 patients with previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age 69 years, performance status 1, and prior chemotherapeutic regimens 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 CR and 10 PR) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with non-hematologic toxicities (nausea/vomiting, mucositis, and anorexia) seen in < 50% of patients. Median hematologic values during the first cycle for this dosage included WBC 1300/mm3, platelets 129,000/mm3, and hemoglobin 10.9 mg/dl. With dose escalation, hematologic toxicity was dose-limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in intravenous form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma. Further studies employing idarubicin in non-Hodgkin's lymphoma should be considered. Cardiac function should be followed in trials utilizing anthracycline-type chemotherapeutic agents.

Authors
Case, DC; Gerber, MC; Gams, RA; Crawford, J; Votaw, ML; Higano, CS; Pruitt, BT; Gould, J
MLA Citation
Case, DC, Gerber, MC, Gams, RA, Crawford, J, Votaw, ML, Higano, CS, Pruitt, BT, and Gould, J. "Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma." Leukemia & lymphoma 10 Suppl (January 1993): 73-79.
PMID
8481674
Source
epmc
Published In
Leukemia & Lymphoma (Informa)
Volume
10 Suppl
Publish Date
1993
Start Page
73
End Page
79
DOI
10.3109/10428199309149116

A comparative study of monoclonal gammopathies and immunoglobulin levels in Japanese and United States elderly.

OBJECTIVE: To define the prevalence of monoclonal immunoglobulin (Ig) proteins and quantitative serum immunoglobulin levels in elderly Japanese in comparison with elderly Caucasians as possible factors related to the reported lower incidence of multiple myeloma in elderly Japanese than in elderly Caucasians. DESIGN: Survey study SETTING: Community Center in Yokohama, Japan and Retirement Community in the United States. PARTICIPANTS: Convenience sample of community-dwelling elderly subjects (age 63-95) presenting for health screening examinations in each setting. Frozen serum samples were obtained from routine screening from 146 consecutive Japanese subjects and 111 US subjects. INTERVENTION: None MEASUREMENTS: Presence of monoclonal immunoglobulin protein determined by serum protein electrophoresis and immunofixation and quantitative Ig by laser nephelometry. RESULTS: Four (2.7%) of the Japanese cohort had monoclonal gammopathies compared with 11 (10%) of the American cohort. Two of the monoclonal gammopathies were IgG Kappa and two were IgG Lambda. No cases of multiple monoclonal gammopathy were identified in the Japanese group, compared with 25% of the monoclonal gammopathies in the American group. The mean quantitative serum IgG level for the Japanese group was 1,685 +/- 520 mg/dL versus 1,118 +/- 402 mg/dL for the American group; mean quantitative IgA levels were 283 +/- 116 mg/dL versus 226 +/- 116 mg/dL (P < 0.001). Albumin levels were normal in both populations, suggesting that there was not an increase in occult inflammatory disorders in the Japanese population. CONCLUSION: The low prevalence of monoclonal gammopathy in elderly Japanese is consistent with the reported lower frequency of multiple myeloma. The reason for the higher quantitative immunoglobulin levels in this population is unclear. Further cross-cultural investigation is warranted to explore the genetic influences on altered immune regulation with aging.

Authors
Bowden, M; Crawford, J; Cohen, HJ; Noyama, O
MLA Citation
Bowden, M, Crawford, J, Cohen, HJ, and Noyama, O. "A comparative study of monoclonal gammopathies and immunoglobulin levels in Japanese and United States elderly." J Am Geriatr Soc 41.1 (January 1993): 11-14.
PMID
8418116
Source
pubmed
Published In
Journal of American Geriatrics Society
Volume
41
Issue
1
Publish Date
1993
Start Page
11
End Page
14

Long-term results of combined modality therapy for esophageal cancer

Authors
Kavanagh, BD; Montana, GS; Crawford, J; Wolfe, WG; Anscher, MS
MLA Citation
Kavanagh, BD, Montana, GS, Crawford, J, Wolfe, WG, and Anscher, MS. "Long-term results of combined modality therapy for esophageal cancer." Radiation Oncology Investigations 1.4 (1993): 227-234.
Source
crossref
Published In
Radiation Oncology Investigations
Volume
1
Issue
4
Publish Date
1993
Start Page
227
End Page
234
DOI
10.1002/roi.2970010406

The impact of therapy with filgrastim (recombinant granulocyte colony-stimulating factor) on the health care costs associated with cancer chemotherapy

The objective of the study was to estimate the net impact on health resource utilisation of using recombinant granulocyte colony-stimulating factor (filgrastim) following myelosuppressive chemotherapy. Cost minimisation of the study medication in a randomised, double-blind, placebo-controlled clinical trial was conducted in teaching institutions and affiliated community hospitals participating in a clinical trial. 68 patients with small cell lung cancer undergoing cyclophosphamide, doxorubicin and etoposide chemotherapy were randomised to blinded placebo or filgrastim study medication at three or 14 clinical trials sites. The patients received daily subcutaneous injections of filgrastim or placebo, initiated 24 h after chemotherapy and continued until the neutrophil count exceeded 10 000 × 106/l after the time of the expected nadir. Differences in total charges, costs and Medicare payments between treatment groups were the main outcomes measured. Compared to placebo patients, filgrastim-treated patients had significantly fewer and less resource-intensive hospitalisations. After accounting for filgrastim purchase and administration, the charge model predicts overall savings from filgrastim use in a clinical setting in which the risk of febrile neutropenia is high for patients not receiving filgrastim. The Medicare and cost models predict only a partial recapture of the cost of filgrastim therapy. The health care resources impact of filgrastim was sensitive to the risk of hospitalisation with febrile neutropenia, and to the perspective chosen for measuring resource utilisation (charges, costs or Medicare payments). The adjunctive use of filgrastim following myelosuppressive chemotherapy leads to partial or complete recapture of the cost of purchasing and administering the product. © 1993.

Authors
Glaspy, JA; Bleecker, G; Crawford, J; Stoller, R; Strauss, M
MLA Citation
Glaspy, JA, Bleecker, G, Crawford, J, Stoller, R, and Strauss, M. "The impact of therapy with filgrastim (recombinant granulocyte colony-stimulating factor) on the health care costs associated with cancer chemotherapy." European Journal of Cancer 29.SUPPL. 7 (1993): S23-S30.
PMID
7508727
Source
scival
Published In
European Journal of Cancer
Volume
29
Issue
SUPPL. 7
Publish Date
1993
Start Page
S23
End Page
S30

Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer.

The present study was undertaken in order to determine the feasibility and efficacy of induction chemotherapy with carboplatin and etoposide, followed by weekly carboplatin and full-course radiotherapy as pre-operative therapy for marginally resectable non-small cell lung cancer (NSCLC). Twenty-eight patients with good Eastern Cooperative Oncology Group (ECOG) performance status ratings and stage IIIA NSCLC received induction chemotherapy with carboplatin (dose computed with the Egorin formula, days 1 and 29) and etoposide (100 mg/m2/day, days 1 through 3 and 29 through 31). This was followed by 100 mg/m2 weekly carboplatin given over 6 weeks, concurrently with 60 Gy radiotherapy. Patients with either responsive or stable disease underwent thoracotomy 4 weeks after the completion of combined-modality therapy. All 28 patients received the first chemotherapy cycle (average carboplatin dose, 407 mg/m2; range, 195 to 586 mg/m2). World Health Organization (WHO) grade 3/4 neutropenia and thrombocytopenia were observed in 53 and 34% of patients, respectively. There were three febrile neutropenic episodes, but no septic deaths. Five patients (18%) required dose reductions prior to the second chemotherapy cycle, but the dose intensity of carboplatin was maintained (average dose, 390 mg/m2; range, 195 to 586 mg/m2). In all, 82% of patients received full-dose radiotherapy, and 73% received at least five of six planned concurrent weekly carboplatin doses. Carboplatin doses were most frequently delayed for thrombocytopenia and/or leukopenia. Carboplatin did not increase the incidence of radiation-induced esophagitis. Only three patients required interruption of radiotherapy, for esophagitis (two patients) and persistent thrombocytopenia (one patient). The response rate to pre-operative therapy was 64%. In this study, we demonstrated the ability to deliver escalated doses of carboplatin with standard-dose etoposide as induction chemotherapy with reasonable myelotoxicity. The combined-modality therapy was well tolerated, and the addition of weekly carboplatin did not result in increased radiation-related toxicity. This neoadjuvant regimen is active in the treatment of locally advanced NSCLC, and compares favorably to other cisplatin-based regimens.

Authors
Deutsch, MA; Leopold, KA; Crawford, J; Wolfe, W; Foster, W; Blackwell, S; Yost, R
MLA Citation
Deutsch, MA, Leopold, KA, Crawford, J, Wolfe, W, Foster, W, Blackwell, S, and Yost, R. "Carboplatin, etoposide, and radiotherapy, followed by surgery, for the treatment of marginally resectable non-small cell lung cancer." Cancer Treat Rev 19 Suppl C (1993): 53-62.
PMID
8221717
Source
pubmed
Published In
Cancer Treatment Reviews
Volume
19 Suppl C
Publish Date
1993
Start Page
53
End Page
62

Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: A randomized trial of the southeastern cancer study group

Purpose: The primary objective of this randomized prospective study was to compare the survival of limited-stage small-cell lung cancer (SCLC) patients treated with chemotherapy alone or chemotherapy plus thoracic radiotherapy (TRT). A secondary objective was to determine the effect of consolidation chemotherapy on survival. Patients and Methods: This multiinstitutional phase III study included 386 patients with limited-stage SCLC. All patients received cyclophosphamide 1,000 mg/m2, doxorubicin 40 mg/m2, and vincristine 1 mg/m2 (CAV) every 3 weeks for six cycles. Irradiated patients received 30 Gy in 10 fractions during weeks 1 and 2 of chemotherapy. Fifteen Gy in five fractions was administered during week 7 (total dose, 45 Gy). Following CAV, responding patients were randomized to receive two cycles of consolidation chemotherapy (cisplatin 20 mg/m2/ d for 4 days plus etoposide 100 mg/m2/d for 4 days) or observation. Results: Complete (46% and 38%; P = .14) and overall response rates (67% and 64%; P = .58) were not statistically significantly different. Although not significantly different, median (14.4 v 12.8 months) and 2-year survival (33% v 23.5%) rates favored the irradiated patients. Grade 4 hematologic toxicity was greater in irradiated patients (60% and 39%; P < .001). Patients given consolidation chemotherapy experienced superior median (21.1 v 13.2 months; P = .028) and 2-year survival (44% v 26%; P = .028) rates. Conclusion: The concurrent use of TRT and CAV chemotherapy as administered in this study failed to improve the survival of limited-stage SCLC patients compared with CAV alone. Life-threatening hematologic toxicities were more frequent with combined-modality therapy. The survival of limited-stage patients treated with CAV (with or without TRT) was improved with two cycles of cisplatin and etoposide consolidation therapy. Whether similar survival results could be achieved with cisplatin and etoposide alone requires additional study. © 1993 by American Society of Clinical Oncology.

Authors
Johnson, DH; Bass, D; Einhorn, LH; Crawford, J; Perez, CA; Bartolucci, A; Omura, GA; Greco, FA
MLA Citation
Johnson, DH, Bass, D, Einhorn, LH, Crawford, J, Perez, CA, Bartolucci, A, Omura, GA, and Greco, FA. "Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: A randomized trial of the southeastern cancer study group." Journal of Clinical Oncology 11.7 (1993): 1223-1229.
PMID
8391064
Source
scival
Published In
Journal of Clinical Oncology
Volume
11
Issue
7
Publish Date
1993
Start Page
1223
End Page
1229

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma

Authors
Jr, DCC; Gerber, MC; Gams, RA; Crawford, J; Votaw, ML; Higano, CS; Pruitt, BT; Gould, J
MLA Citation
Jr, DCC, Gerber, MC, Gams, RA, Crawford, J, Votaw, ML, Higano, CS, Pruitt, BT, and Gould, J. "Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma." Leukemia and Lymphoma 10.SUPPL. (1993): 73-79.
Source
scival
Published In
Leukemia and Lymphoma
Volume
10
Issue
SUPPL.
Publish Date
1993
Start Page
73
End Page
79

Modulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a phase I trial.

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance may be mediated by repair of chloroethylated guanine before stable cross-linking occurs. Guanine adducts may be repaired by the enzyme O6-alkylguanine-DNA alkyltransferase (O6-AGAT). Such repair irreversibly inactivates O6-AGAT. Streptozotocin (STZ) forms adducts at the O6 position of guanine; repair of these adducts consumes O6-AGAT. In vivo STZ potentiates BCNU cytotoxicity. The purpose of this trial was to determine the maximum tolerated dose of BCNU that can be administered together with STZ. The STZ dose was 500 mg/m2/day for 4 days and was not escalated. BCNU was given 4 h after the third dose of STZ at a starting dose of 75 mg/m2. A total of 43 patients were entered in the study. There were 4 dose escalations, reaching a maximum tolerated BCNU dose of 175 mg/m2. At this dose, thrombocytopenia was the dose-limiting toxicity (one patient, 25-49 x 10(9)/liter; 2 patients, less than 25 x 10(9)/liter); neutropenia was less severe (2 patients, 2.0-3.9 x 10(9)/liter, 1 patient, 1.0-1.9 x 10(9)/liter). Two other commonly seen toxicities were elevations in the serum alkaline phosphatase and mild elevations in the serum creatinine. Peripheral blood lymphocyte O6-AGAT levels decreased from a mean of 212 fmol/mg protein pretherapy to 8.2 fmol/mg protein on day 3 prior to BCNU (P = 0.03). Three partial responses were seen. There were no therapy-related fatalities, and toxicity was easily managed. This study established that 150 mg of BCNU can be administered safely together with STZ, 500 mg/m2/day for 4 days. Additional studies are required to determine whether O6-AGAT-mediated BCNU resistance is suppressed.

Authors
Panella, TJ; Smith, DC; Schold, SC; Rogers, MP; Winer, EP; Fine, RL; Crawford, J; Herndon, JE; Trump, DL
MLA Citation
Panella, TJ, Smith, DC, Schold, SC, Rogers, MP, Winer, EP, Fine, RL, Crawford, J, Herndon, JE, and Trump, DL. "Modulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a phase I trial." Cancer Res 52.9 (May 1, 1992): 2456-2459.
PMID
1533174
Source
pubmed
Published In
Cancer Research
Volume
52
Issue
9
Publish Date
1992
Start Page
2456
End Page
2459

Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.

PURPOSE: The trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone. PATIENTS AND METHODS: In this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP). RESULTS: There were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non-statistically significant trend toward a longer median time to progression with alternating therapy (4.3 months, 4.0 months, 5.2 months, respectively). Crossover second-line chemotherapy given at progression produced low response rates and short survival, regardless of the regimen used. Myelosuppression was the dose-limiting toxicity for all patients, although the pattern and severity differed among the treatment arms. CONCLUSIONS: The combination regimens EP and CAV can be considered equivalently effective induction therapies in extensive SCLC, and these two regimens are, to some degree, crossresistant. Alternating therapy provides no therapeutic advantage compared with the use of either of these regimens alone and should not be considered as standard treatment in this clinical setting.

Authors
Roth, BJ; Johnson, DH; Einhorn, LH; Schacter, LP; Cherng, NC; Cohen, HJ; Crawford, J; Randolph, JA; Goodlow, JL; Broun, GO
MLA Citation
Roth, BJ, Johnson, DH, Einhorn, LH, Schacter, LP, Cherng, NC, Cohen, HJ, Crawford, J, Randolph, JA, Goodlow, JL, and Broun, GO. "Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group." J Clin Oncol 10.2 (February 1992): 282-291.
PMID
1310103
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
10
Issue
2
Publish Date
1992
Start Page
282
End Page
291
DOI
10.1200/JCO.1992.10.2.282

The role of colony stimulating factors as an adjunct to lung cancer chemotherapy: A commentary

Authors
Crawford, J; Green, MR
MLA Citation
Crawford, J, and Green, MR. "The role of colony stimulating factors as an adjunct to lung cancer chemotherapy: A commentary." Lung Cancer 8.3-4 (1992): 153-158.
Source
scival
Published In
Lung Cancer
Volume
8
Issue
3-4
Publish Date
1992
Start Page
153
End Page
158

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma

Idarubicin, a new analogue of daunorubicin, was administered i.v. at a dose of 15 mg/m2 to 31 previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age, 69 years; performance status, 1; and prior chemotherapeutic regimens, 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 complete remission and 10 partial remission) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with nonhematological toxicities (nausea/vomiting, mucositis, and anorexia) seen in <50% of patients. Median hematological values during the first cycle for this dosage included WBC, 1,300/mm3; platelets, 129,000/mm3; and hemoglobin, 10.9 mg/dl. With dose escalation, hematological toxicity was dose limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in i.v. form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma.

Authors
Jr, DCC; Gerber, MC; Gams, RA; Crawford, J; Votaw, ML; Higano, CS; Pruitt, BT; Gould, J
MLA Citation
Jr, DCC, Gerber, MC, Gams, RA, Crawford, J, Votaw, ML, Higano, CS, Pruitt, BT, and Gould, J. "Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma." Cancer Research 52.14 (1992): 3871-3874.
PMID
1617662
Source
scival
Published In
Cancer Research
Volume
52
Issue
14
Publish Date
1992
Start Page
3871
End Page
3874

Colony-stimulating factors: Clinical applications

Recombinant human colony-stimulating factors (CSFs) have potential for wide use in the areas of oncology and infectious disease. Granulocyte CSF and granulocyte-macrophage CSF currently are approved for use in the treatment of neutropenia associated with standard-dose cancer chemotherapy and bone marrow transplantation, respectively. Other settings in which these agents have shown promise are dose-intensive chemotherapy, enhancement of progenitor cell support, primary and acquired neutropenias, myelodysplasia, aplastic anemia, and cytopenias associated with human immunodeficiency virus infection or myelosuppressive therapies for such infection or related conditions. Clinical findings in these areas are encouraging, and potential exists for additional applications of the CSFs.

Authors
Blackwell, S; Crawford, J
MLA Citation
Blackwell, S, and Crawford, J. "Colony-stimulating factors: Clinical applications." Pharmacotherapy 12.2 II (1992): 20S-31S.
PMID
1598311
Source
scival
Published In
Pharmacotherapy
Volume
12
Issue
2 II
Publish Date
1992
Start Page
20S
End Page
31S

Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990

From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses ≥ 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19 103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25 103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving ≥ 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus. © 1992.

Authors
Kavanagh, B; Anscher, M; Leopold, K; Deutsch, M; Gaydica, E; Dodge, R; Allen, K; Allen, D; Staub, EW; Montana, G; Crawford, J; Wolfe, W
MLA Citation
Kavanagh, B, Anscher, M, Leopold, K, Deutsch, M, Gaydica, E, Dodge, R, Allen, K, Allen, D, Staub, EW, Montana, G, Crawford, J, and Wolfe, W. "Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990." International Journal of Radiation Oncology, Biology, Physics 24.4 (1992): 633-642.
PMID
1429085
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
24
Issue
4
Publish Date
1992
Start Page
633
End Page
642

Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer.

BACKGROUND: Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. METHODS: Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, less than 1.0 x 10(9) per liter, with a temperature greater than or equal to 38.2 degrees C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. RESULTS: The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P less than 0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, less than 0.5 x 10(9) per liter) was six days with placebo as compared with one day with G-CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. CONCLUSIONS: The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.

Authors
Crawford, J; Ozer, H; Stoller, R; Johnson, D; Lyman, G; Tabbara, I; Kris, M; Grous, J; Picozzi, V; Rausch, G
MLA Citation
Crawford, J, Ozer, H, Stoller, R, Johnson, D, Lyman, G, Tabbara, I, Kris, M, Grous, J, Picozzi, V, and Rausch, G. "Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer." N Engl J Med 325.3 (July 18, 1991): 164-170.
PMID
1711156
Source
pubmed
Published In
The New England journal of medicine
Volume
325
Issue
3
Publish Date
1991
Start Page
164
End Page
170
DOI
10.1056/NEJM199107183250305

Anti-inflammatory effects of pentoxifylline in claudication.

We measured neutrophil elastase/alpha 1 proteinase inhibitor complex (E/alpha) levels by ELISA in plasma samples drawn from 19 patients with claudication, before and at 1 and 2 months after initiation of pentoxifylline (PTF), 400 mg. p.o. tid. Plasma E/alpha levels declined in all eight patients whose initial values were more than 300 ng elastase per ml. Whole blood viscosity (wbv) was reduced by two months' treatment in 12 of 14 patients tested. The relative change in wbv was significantly related to the relative change in E/alpha (R2 = 0.8), for patients with elevated initial E/alpha levels, suggesting a common or related mechanism for the two effects. Plasma crosslinked fibrin D-dimer fragments (XDP) measured by ELISA as indicators of coagulation activity were lower compared to pretreatment levels in 9 of 10 samples drawn when symptoms were improved on PTF, whereas they were increased in 6 of 9 samples drawn when symptoms were worse or unchanged. Plasma viscosity, C-reactive protein and alpha 1-acid-glycoprotein did not change significantly with PTF treatment. Together these findings are consistent with the possibility that reduced microvascular neutrophil activation and coagulation play a role in the clinical efficacy of PTF in intermittent claudication.

Authors
Currie, MS; Simel, DL; Christenson, RH; Holmes, C; Crawford, J; Cohen, HJ; Rao, KM
MLA Citation
Currie, MS, Simel, DL, Christenson, RH, Holmes, C, Crawford, J, Cohen, HJ, and Rao, KM. "Anti-inflammatory effects of pentoxifylline in claudication." Am J Med Sci 301.2 (February 1991): 85-90.
PMID
2012105
Source
pubmed
Published In
American Journal of the Medical Sciences
Volume
301
Issue
2
Publish Date
1991
Start Page
85
End Page
90

G-CSF for fever and neutropenia induced by chemotherapy [1]

Authors
Stein, RS; Hamm, JT; Higa, GM; Auchter, RM; Crawford, J; Glaspy, JA
MLA Citation
Stein, RS, Hamm, JT, Higa, GM, Auchter, RM, Crawford, J, and Glaspy, JA. "G-CSF for fever and neutropenia induced by chemotherapy [1]." New England Journal of Medicine 326.4 (1991): 269-270.
Source
scival
Published In
New England Journal of Medicine
Volume
326
Issue
4
Publish Date
1991
Start Page
269
End Page
270

Improved survival in advanced Hodgkin's disease with the use of combined modality therapy.

To compare the effectiveness of combined modality therapy and chemotherapy alone for the treatment of advanced Hodgkin's disease (Stages IIB-IV), records of 154 patients who achieved a complete or partial response to induction combination chemotherapy were analyzed. Sixty-seven patients received consolidation radiotherapy and 87 patients received no further treatment. Thirty of 154 patients participated in a prospective randomized trial of the Southeastern Cancer Study Group (SEG). Ten-year actuarial survival (Hodgkin's disease deaths only) was 93% for the combined modality therapy patients compared with 59% for the chemotherapy alone patients (p less than 0.0005). Combined modality therapy patients had an 87% 10-year actuarial freedom from relapse as opposed to 56% for the chemotherapy alone patients (p less than 0.0005). Relapse occurred in 33 of the chemotherapy alone patients, 28 (85%) being in sites involved at initial diagnosis. Seven combined modality therapy patients recurred with only two true in-field failures. Multi-variate analysis demonstrated treatment (combined modality) as the only variable affecting outcome. Patients prospectively treated with combined modality therapy in the Southeastern Cancer Study Group trial also showed a statistically significant improvement in both survival and freedom from relapse compared with patients receiving chemotherapy only. There was no apparent increase in toxicity from using combined modality therapy compared with chemotherapy. Three chemotherapy patients and one combined modality therapy patients developed acute leukemia.

Authors
Brizel, DM; Winer, EP; Prosnitz, LR; Scott, J; Crawford, J; Moore, JO; Gockerman, JP
MLA Citation
Brizel, DM, Winer, EP, Prosnitz, LR, Scott, J, Crawford, J, Moore, JO, and Gockerman, JP. "Improved survival in advanced Hodgkin's disease with the use of combined modality therapy." Int J Radiat Oncol Biol Phys 19.3 (September 1990): 535-542.
PMID
2211201
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
19
Issue
3
Publish Date
1990
Start Page
535
End Page
542

Effects of pentoxifylline administration on blood viscosity and leukocyte cytoskeletal function in patients with intermittent claudication.

We have previously shown that pentoxifylline, a drug used in intermittent claudication, causes depolymerization of actin in leukocytes in vitro. In this study we evaluated several parameters in peripheral blood obtained from 17 patients receiving pentoxifylline, before therapy and at 1 and 2 months after initiation of drug therapy. Total blood viscosity decreased at 1 month and was further reduced at 2 months. The plasma viscosity remained unchanged during the course of the therapy (1.770 +/- 0.147, 1.776 +/- 0.162, and 1.772 +/- 0.164 centipoise at 0, 1, and 2 months, respectively; mean +/- SD, n = 14 to 17). No changes were observed in stimulus-induced actin polymerization in granulocytes, concanavalin A-induced capping in granulocytes and lymphocytes, and anti-IgG-induced caps in lymphocytes, before and after therapy. Similarly, there was no difference in the magnitude of depolymerization caused by pentoxifylline when added in vitro. Thus none of the parameters altered by pentoxifylline treatment in vitro have been observed ex vivo in patients receiving this drug. However, the decrease in total blood viscosity along with unaltered plasma viscosity suggests that the rheology of the cellular elements is being affected by the administered drug. In addition to the direct effects on the cell membrane and the cytoskeleton, pentoxifylline may exert indirect effects through its inhibitory action on cytokine production. Subtle changes in a number of parameters in leukocytes, which taken alone fail to show demonstrable changes, might ultimately be responsible for the therapeutic benefit noted with pentoxifylline.

Authors
Rao, KM; Simel, DL; Cohen, HJ; Crawford, J; Currie, MS
MLA Citation
Rao, KM, Simel, DL, Cohen, HJ, Crawford, J, and Currie, MS. "Effects of pentoxifylline administration on blood viscosity and leukocyte cytoskeletal function in patients with intermittent claudication." J Lab Clin Med 115.6 (June 1990): 738-744.
PMID
2366034
Source
pubmed
Published In
Journal of Laboratory and Clinical Medicine
Volume
115
Issue
6
Publish Date
1990
Start Page
738
End Page
744

Correlation between erythrocyte CR1 reduction and other blood proteinase markers in patients with malignant and inflammatory disorders.

Erythrocyte CR1, a C3b/C4b-binding complement-regulatory protein, is sensitive to proteolysis in vitro. To test the hypothesis that in vivo erythrocyte CR1 reduction results from intravascular proteinase activities, we used enzyme-linked immunosorbent assays to measure gamma-crosslinked fibrin degradation products (D-dimers) as indicators of coagulation/fibrinolytic activity, and complexes of neutrophil elastase with alpha 1 proteinase inhibitor (E/A) as indicators of neutrophil enzyme release in malignant and inflammatory disorders. Erythrocyte CR1, measured by monoclonal anti-CR1 antibody binding, was inversely related to disease activity and blood proteinase markers. Levels of erythrocyte CR1 were significantly lower for patients with active versus remittent squamous and small cell lung cancers, Hodgkin's and diffuse large cell lymphomas, and acute myelogenous leukemias. In patients with active thoracic cancers, elevated D-dimer levels correlated with reduction of CR1. In patients with rheumatoid arthritis, CR1 reduction was correlated with elevated levels of elastase complexes. Our findings substantiate the relationship of acquired CR1 reduction to the activity of certain diseases and provide circumstantial support for the hypothesis that erythrocyte CR1 is lost to proteolysis in vivo. Although heritable differences in CR1 expression reduce the interpretability of single measurements of erythrocyte CR1 levels, disease-associated CR1 reduction may be a useful indicator of disorders with chronically increased blood proteinase activity.

Authors
Currie, MS; Vala, M; Pisetsky, DS; Greenberg, CS; Crawford, J; Cohen, HJ
MLA Citation
Currie, MS, Vala, M, Pisetsky, DS, Greenberg, CS, Crawford, J, and Cohen, HJ. "Correlation between erythrocyte CR1 reduction and other blood proteinase markers in patients with malignant and inflammatory disorders." Blood 75.8 (April 15, 1990): 1699-1704.
PMID
2158365
Source
pubmed
Published In
Blood
Volume
75
Issue
8
Publish Date
1990
Start Page
1699
End Page
1704

Development of multiple monoclonal serum immunoglobulins (multiclonal gammopathy) following both HLA-identical unfractionated and T cell-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency.

We have identified five patients with severe combined immunodeficiency (SCID) who developed multiple monoclonal serum immunoglobulin components (multiclonal gammopathy) following bone marrow transplantation. Four patients received haploidentical bone marrow stem cells depleted of T cells and other mature marrow cells by soy lectin agglutination and/or sheep erythrocyte rosetting. One patient received unfractionated HLA-identical bone marrow. Twenty-one distinct paraproteins were detected: 14 IgG, 5 IgM, and 2 IgA, all containing either kappa or lambda light chains. In the haploidentical stem-cell recipients, these monoclonal immunoglobulins appeared immediately prior to, or concomitant with, a rise in T-cell numbers and function. Resolution or diminution of this multiclonal gammopathy occurred as T-cell function was established. Posttransplant karyotypic analyses revealed PHA-stimulated T cells to be of donor origin in all patients. Karyotyping of B-cell lines posttransplantation revealed them to be 100% donor in the patient receiving unfractionated HLA-identical marrow and 100% host (1/4), 100% donor (1/4), mixed (1/4), or not tested (1/4) in the patients receiving haploidentical marrow stem cells. There was no evidence of Epstein-Barr virus (EBV) infection in any of the patients. All patients are currently alive and well. Immunoglobulin synthesis is normal in the patient who received the HLA-identical marrow but remains below normal in the four patients who received T cell-depleted haploidentical stem cells. The posttransplantation development of monoclonal immunoglobulins in the absence of EBV infection did not adversely affect the outcome of either HLA-identical marrow or haploidentical stem-cell grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Kent, EF; Crawford, J; Cohen, HJ; Buckley, RH
MLA Citation
Kent, EF, Crawford, J, Cohen, HJ, and Buckley, RH. "Development of multiple monoclonal serum immunoglobulins (multiclonal gammopathy) following both HLA-identical unfractionated and T cell-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency." J Clin Immunol 10.2 (March 1990): 106-114.
PMID
2338452
Source
pubmed
Published In
Journal of Clinical Immunology
Volume
10
Issue
2
Publish Date
1990
Start Page
106
End Page
114

Stimulus-specific effects of pentoxifylline on neutrophil CR3 expression, degranulation, and superoxide production.

The effects of pentoxifylline (Trental) on human neutrophil CR3 up-modulation, degranulation, and superoxide production were studied. We used the chemotactic peptide fMLP and the phorbol ester PMA as soluble stimuli, and beta-glucan particles as a CR3-specific solid phase stimulus of neutrophil superoxide production. Since neutrophils have adenosine A2 receptors, we compared effects of pentoxifylline to effects of adenosine, and we also looked at the effect of cytochalasin B, which breaks up actin filaments. Pentoxifylline inhibited both CR3 up-modulation and degranulation of myeloperoxidase and lysozyme. Pentoxifylline is a more potent inhibitor of fMLP- compared to PMA-induced degranulation, and is especially potent against superoxide production. While pentoxifylline is less potent than adenosine in its inhibition of fMLP-induced superoxide production, it is more potent in its inhibition of PMA- and beta-glucan particle-stimulated superoxide production. Cytochalasin B, which enhances degranulation and fMLP-stimulated superoxide production, was found to inhibit beta-glucan particle-stimulated superoxide production. These findings are consistent with the hypothesis that pentoxifylline can affect both the cytoskeletal architecture of unstimulated neutrophils and the activation and responses of neutrophils which involve actin polymerization and receptor-cytoskeletal interactions.

Authors
Currie, MS; Rao, KM; Padmanabhan, J; Jones, A; Crawford, J; Cohen, HJ
MLA Citation
Currie, MS, Rao, KM, Padmanabhan, J, Jones, A, Crawford, J, and Cohen, HJ. "Stimulus-specific effects of pentoxifylline on neutrophil CR3 expression, degranulation, and superoxide production." J Leukoc Biol 47.3 (March 1990): 244-250.
PMID
2155276
Source
pubmed
Published In
Journal of leukocyte biology
Volume
47
Issue
3
Publish Date
1990
Start Page
244
End Page
250

An in vitro analogue of immune dysfunction with altered immunoglobulin production in the aged.

The consequences of aging of the immune system include impaired T-lymphocyte responsiveness and aberrant immunoglobulin production. Although T cells from elderly individuals have a well-described defect in lymphoblastic transformation in response to some polyclonal mitogens, immunoglobulin abnormalities have lacked a clear in vitro model. Peripheral blood mononuclear cells from 13 young and 13 old healthy donors were cultured with phytohemagglutinin (PHA) or pokeweed mitogen (PWM). Old-donor-cell phytohemagglutinin (PHA), but not PWM, cultures had significantly lower lymphoblastic transformation compared with young donor cultures. IgG, IgA, and IgM production tended to be lower in old- versus young-donor PWM cell cultures. By contrast, despite lower lymphoblastic transformation in old-donor PHA cell cultures, immunoglobulin production was higher for old- versus young-donor cell cultures. No significant age differences were present in initial lymphocyte counts, percent B cells, T cells or monocytes, or helper/suppressor ratios to explain this enhancement in immunoglobulin production. PHA-stimulated mononuclear cell cultures in the aged demonstrate not only a defect in proliferation but also increased immunoglobulin production. This in vitro system may be useful to characterize further the pathogenesis of altered immunoglobulin production in the elderly.

Authors
Crawford, J; Oates, S; Wolfe, LA; Cohen, HJ
MLA Citation
Crawford, J, Oates, S, Wolfe, LA, and Cohen, HJ. "An in vitro analogue of immune dysfunction with altered immunoglobulin production in the aged." J Am Geriatr Soc 37.12 (December 1989): 1140-1146.
PMID
2592721
Source
pubmed
Published In
Journal of American Geriatrics Society
Volume
37
Issue
12
Publish Date
1989
Start Page
1140
End Page
1146

Hyperviscosity syndrome in association with kappa light chain myeloma.

Authors
Carter, PW; Cohen, HJ; Crawford, J
MLA Citation
Carter, PW, Cohen, HJ, and Crawford, J. "Hyperviscosity syndrome in association with kappa light chain myeloma." Am J Med 86.5 (May 1989): 591-595.
PMID
2496600
Source
pubmed
Published In
The American Journal of Medicine
Volume
86
Issue
5
Publish Date
1989
Start Page
591
End Page
595

Hodgkin's disease presenting as myelofibrosis

Four patients with Hodgkin's disease and bone marrow fibrosis are presented in whom the clinical presentation was dominated by cytopenias; this was associated with a delayed diagnosis for an average of 20 months. Despite marrow involvement, chemotherapy resulted in complete remissions and two patients appear to have been cured. Marrow fibrosis resolved at least partially after chemotherapy. The medical literature relevant to bone marrow involvement by Hodgkin's disease is reviewed. Hodgkin's disease should be considered in the differential diagnosis of idiopathic myelofibrosis.

Authors
Meadows, LM; Rosse, WR; Moore, JO; Crawford, J; Laszlo, J; Kaufman, RE
MLA Citation
Meadows, LM, Rosse, WR, Moore, JO, Crawford, J, Laszlo, J, and Kaufman, RE. "Hodgkin's disease presenting as myelofibrosis." Cancer 64.8 (1989): 1720-1726.
PMID
2790685
Source
scival
Published In
Cancer
Volume
64
Issue
8
Publish Date
1989
Start Page
1720
End Page
1726

Actin depolymerization and inhibition of capping induced by pentoxifylline in human lymphocytes and neutrophils.

Pentoxifylline is used clinically for the treatment of intermittent claudication. It is believed to exert its effect by altering the rheologic properties of blood. The cytoskeleton plays an important role in the maintenance of cell structure and function. In particular, alterations in the state of actin seem to play an important role in cell motility. Therefore, we examined the effect of pentoxifylline on the actin state in human polymorphonuclear leukocytes (PMN) and mononuclear cells. Pentoxifylline (10 mM final concentration) decreased F-actin content in both PMN and mononuclear cells. Pentoxifylline also inhibited concanavalin A-induced capping in PMN and mononuclear cells. Similarly, surface immunoglobulin capping in B lymphocytes was also inhibited. Pretreatment of cells with pertussis toxin did not inhibit pentoxifylline-induced decrease in F-actin, suggesting pentoxifylline does not act through pertussis toxin-sensitive G-proteins. Dibutyryl cyclic AMP failed to show any significant effect on the F-actin content in PMN. Therefore, the effect of pentoxifylline cannot be attributed to changes in cyclic AMP levels. Chemotactic peptide-induced actin polymerization was unaffected in PMN when expressed as percent changes in F-actin. The observations reported here suggest that the rheological effects of pentoxifylline might be due to its effects on the actin state in the cellular elements of the blood. Further studies on the mechanism of action of pentoxifylline on actin state in leukocytes will prove useful in delineating the physiological mechanisms regulating actin state in leukocytes.

Authors
Rao, KM; Crawford, J; Currie, MS; Cohen, HJ
MLA Citation
Rao, KM, Crawford, J, Currie, MS, and Cohen, HJ. "Actin depolymerization and inhibition of capping induced by pentoxifylline in human lymphocytes and neutrophils." J Cell Physiol 137.3 (December 1988): 577-582.
PMID
2848043
Source
pubmed
Published In
Journal of Cellular Physiology
Volume
137
Issue
3
Publish Date
1988
Start Page
577
End Page
582
DOI
10.1002/jcp.1041370326

Lung cancer in the elderly.

Authors
O'Rourke, MA; Crawford, J
MLA Citation
O'Rourke, MA, and Crawford, J. "Lung cancer in the elderly." Compr Ther 14.6 (June 1988): 47-54. (Review)
PMID
3046836
Source
pubmed
Published In
Comprehensive therapy
Volume
14
Issue
6
Publish Date
1988
Start Page
47
End Page
54

Sinus histiocytosis with massive lymphadenopathy. Case report and review of a multisystemic disease with cutaneous infiltrates.

A report of a patient with the rare syndrome of sinus histiocytosis with massive lymphadenopathy is presented here. This patient is unusual in several respects, including his longevity after diagnosis, the presence of a benign monoclonal gammopathy, and the characterization of his cutaneous infiltrates by immunofluorescent monoclonal antibody markers. A review of the literature on sinus histiocytosis with massive lymphadenopathy, with particular emphasis on cutaneous manifestations, is given.

Authors
Olsen, EA; Crawford, JR; Vollmer, RT
MLA Citation
Olsen, EA, Crawford, JR, and Vollmer, RT. "Sinus histiocytosis with massive lymphadenopathy. Case report and review of a multisystemic disease with cutaneous infiltrates." J Am Acad Dermatol 18.6 (June 1988): 1322-1332. (Review)
PMID
3290288
Source
pubmed
Published In
Journal of The American Academy of Dermatology
Volume
18
Issue
6
Publish Date
1988
Start Page
1322
End Page
1332

Erythrocyte anisocytosis. Visual inspection of blood films vs automated analysis of red blood cell distribution width.

An improved anemia classification may be available by combining measures of red blood cell size variability with mean corpuscular volume. Visual inspection of the peripheral blood film allows semiquantitative description of anisocytosis while quantitative measures are determined from electronic cell counter analyzers' red blood cell distribution width. We evaluated correlations between semiquantitative and quantitative measures of anisocytosis for different groups of observers. Hematologists', medical students', and medical residents' semiquantitative assessment of anisocytosis correlated with the quantitative red blood cell distribution width. The interobserver variability demonstrated that all observers correlated with each other, while the intraobserver variability of semiquantitative anisocytosis demonstrated that observers were more precise than could be predicted by chance. However, the extreme precision of the red blood cell distribution width strongly suggests that it should be the "gold standard" for measuring red blood cell size variability.

Authors
Simel, DL; DeLong, ER; Feussner, JR; Weinberg, JB; Crawford, J
MLA Citation
Simel, DL, DeLong, ER, Feussner, JR, Weinberg, JB, and Crawford, J. "Erythrocyte anisocytosis. Visual inspection of blood films vs automated analysis of red blood cell distribution width." Arch Intern Med 148.4 (April 1988): 822-824.
PMID
3355302
Source
pubmed
Published In
Archives of internal medicine
Volume
148
Issue
4
Publish Date
1988
Start Page
822
End Page
824

Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer

From June 1982 through October 1985, the Southeastern Cancer Study Group randomized patients with limited small-cell lung cancer (SCLC) to cyclophosphamide plus doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) plus vincristine (CAV) for six cycles v CAV plus concomitant thoracic irradiation as induction therapy. Patients achieving either a complete or partial response and remaining in remission after completion of induction therapy were subsequently randomized to consolidation chemotherapy consisting of cisplatin 20 mg/m2 x 4 plus etoposide (VP-16) 100 mg/m2 x 4 every 4 weeks for two courses v no further therapy. There were 160 patients entered on the consolidation phase and 148 were fully evaluable. The median survival for patients randomized to cisplatin plus VP-16 (PVP16) from start of CAV chemotherapy was 97.7 weeks, compared with 68 weeks for the no-consolidation arm (P = .0094). PVP16 consolidation also significantly increased the duration of remission, with median durations of 49 weeks v 28 weeks (P = .0008). The median durations for partial remission were 41 weeks v 23 weeks (P = .013), and for complete remission, 52 weeks v 30.5 weeks (P = .0091). Furthermore, 18 patients on PVP16 consolidation remain in a continuous complete remission for 12+ months and 13 of these are continuously disease free 2+ years. Eight patients randomized to no consolidation remain in a continuous complete remission, with only four patients disease free 2+ years. PVP16 consolidation has significantly improved the duration of remission and overall survival and appears capable of improving the cure rate in limited SCLC.

Authors
Einhorn, LH; Crawford, J; Birch, R; Omura, G; Johnson, DH; Greco, FA
MLA Citation
Einhorn, LH, Crawford, J, Birch, R, Omura, G, Johnson, DH, and Greco, FA. "Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer." Journal of Clinical Oncology 6.3 (1988): 451-456.
PMID
2832549
Source
scival
Published In
Journal of Clinical Oncology
Volume
6
Issue
3
Publish Date
1988
Start Page
451
End Page
456

Lung cancer in the elderly.

Half of all lung cancers occur in persons aged 65 years and older. The symptoms of lung cancer in the elderly may be nonspecific and misleading. Age trends in incidence, histologic subtype, and stage suggest that selective screening of older persons for lung cancer should be studied. Recent data reveal that the mortality risk for lung cancer surgery in selected elderly patients is comparable to that for younger patients. Age alone should not deny older lung cancer patients optimal evaluation, treatment, and care.

Authors
O'Rourke, MA; Crawford, J
MLA Citation
O'Rourke, MA, and Crawford, J. "Lung cancer in the elderly." Clin Geriatr Med 3.4 (November 1987): 595-623. (Review)
PMID
2445460
Source
pubmed
Published In
Clinics in Geriatric Medicine
Volume
3
Issue
4
Publish Date
1987
Start Page
595
End Page
623

Relationship of cancer and aging.

The major risk factor for cancer is progressive age. Molecular advances in our understanding of carcinogenesis and the aging process are helping to clarify this relationship. The magnitude of cancer in the elderly warrants institution of an active prevention program by clinicians caring for this population.

Authors
Crawford, J; Cohen, HJ
MLA Citation
Crawford, J, and Cohen, HJ. "Relationship of cancer and aging." Clin Geriatr Med 3.3 (August 1987): 419-432. (Review)
PMID
3308041
Source
pubmed
Published In
Clinics in Geriatric Medicine
Volume
3
Issue
3
Publish Date
1987
Start Page
419
End Page
432

Pulmonary hypertension secondary to serum hyperviscosity in a patient with rheumatoid arthritis.

A patient with rheumatoid arthritis who was evaluated for dyspnea of six months' duration is described. Although no primary cardiac or parenchymal lung disease was identified, right heart catheterization revealed marked pulmonary hypertension. The patient was presumed to have pulmonary arteritis. Evaluation of her hyperproteinemia, however, led to the discovery of a polyclonal gammopathy with a marked increase in plasma viscosity. Although the classic clinical findings of the hyperviscosity syndrome were minimal, the patient underwent plasmapheresis, resulting in a marked reduction of pulmonary artery pressures (from 53 +/- 4 mm Hg, mean +/- SD, to 30 +/- 3 mm Hg, p less than 0.05) and pulmonary vascular resistance (from 707 +/- 63 dynes/second/cm5 to 421 +/- 72 dynes/second/cm5, p less than 0.05) concomitant with a return to normal plasma viscosity. Her dyspnea completely resolved. This represents the first successful treatment of pulmonary hypertension by plasmapheresis. Protein evaluation revealed the presence of intermediate complexes of IgG rheumatoid factor. The hyperviscosity syndrome should be considered in the differential diagnosis of pulmonary hypertension in patients with rheumatoid arthritis and other disorders associated with a polyclonal or monoclonal gammopathy. Pulmonary hypertension secondary to the hyperviscosity syndrome is reversible by plasmapheresis. Immunosuppressive therapy that reduces immunoglobulin production may provide a means of long-term treatment.

Authors
Eaton, AM; Serota, H; Kernodle, GW; Uglietta, JP; Crawford, J; Fulkerson, WJ
MLA Citation
Eaton, AM, Serota, H, Kernodle, GW, Uglietta, JP, Crawford, J, and Fulkerson, WJ. "Pulmonary hypertension secondary to serum hyperviscosity in a patient with rheumatoid arthritis." Am J Med 82.5 (May 1987): 1039-1045.
PMID
3578340
Source
pubmed
Published In
The American Journal of Medicine
Volume
82
Issue
5
Publish Date
1987
Start Page
1039
End Page
1045

Clinical utility of erythrocyte sedimentation rate and plasma protein analysis in the elderly.

The utilization and interpretation of the erythrocyte sedimentation rate in the elderly have been surrounded by controversy and confusion. To improve the understanding of the erythrocyte sedimentation rate and its determinants in the aged, a defined population of 111 ambulatory, retirement-home residents underwent thorough clinical and laboratory evaluation. Westergren erythrocyte sedimentation rate, Wintrobe erythrocyte sedimentation rate, and plasma viscosity measurements were all significantly correlated with one another as well as with plasma proteins, particularly fibrinogen and globulins. Age per se had no influence on the erythrocyte sedimentation rate in the study population. On the basis of standard upper limits of normal for younger populations, the Wintrobe sedimentation rate was most commonly abnormal and plasma viscosity least commonly abnormal. The "normal" upper limit of 20 mm/hour for Westergren sedimentation rate was also the optimal limit of normal by receiver operating characteristic analysis of the study population. Although the sensitivity of the Westergren sedimentation rate for the presence of an inflammatory condition or monoclonal gammopathy was only 0.55, the specificity was 0.96, and the positive predictive value of an elevated erythrocyte sedimentation rate being associated with a clinical disorder was 0.93. The enhanced clinical utility of the erythrocyte sedimentation rate in this population compared with other elderly populations may be due to a low prevalence of anemia and hypoalbuminemia. In such populations, the erythrocyte sedimentation rate may remain a useful clinical test, regardless of patient age.

Authors
Crawford, J; Eye-Boland, MK; Cohen, HJ
MLA Citation
Crawford, J, Eye-Boland, MK, and Cohen, HJ. "Clinical utility of erythrocyte sedimentation rate and plasma protein analysis in the elderly." Am J Med 82.2 (February 1987): 239-246.
PMID
3812516
Source
pubmed
Published In
The American Journal of Medicine
Volume
82
Issue
2
Publish Date
1987
Start Page
239
End Page
246

Evaluation of monoclonal gammopathies in the "well" elderly.

The study of monoclonal gammopathies in the elderly provides an opportunity to define immunologic and neoplastic changes with aging. Previous reports using paper and cellulose acetate electrophoresis have documented an age-related increase in monoclonal gammopathies. In this study, the more sensitive techniques of high-resolution agarose gel electrophoresis and immunofixation were used, in conjunction with other protein studies, to further evaluate the prevalence of monoclonal gammopathies in 111 ambulatory residents (aged 62 to 95) of a retirement home. Eleven of the 111 residents (10 percent) were found to have a monoclonal gammopathy, ranging in concentration from 0.2 to 1.8 g/dl. All monoclonal gammopathies were confirmed by immunofixation, which also documented the presence of additional unsuspected monoclonal components in three of the 11 residents. The prevalence of monoclonal gammopathies by age ranged from 6 percent in the group younger than 80 years of age to 14 percent in the group older than 90 years of age. Only one of the 11 residents had any clinical or routine laboratory suggestion of a monoclonal gammopathy. The other 10 had normal ratios of total protein and albumin to globulin. Five of the 11 (45 percent) had an otherwise clinically unexplained erythrocyte sedimentation rate of more than 20 mm/hour, compared with only two of 100 in the group without monoclonal gammopathies. Follow-up studies one to three years after initial evaluation revealed that five of the 11 patients had died, two with evidence of disease progression. In the other six patients, monoclonal protein concentration and other protein values remained stable. An unexplained elevation of the erythrocyte sedimentation rate in the elderly warrants investigation for the presence of a monoclonal gammopathy. Agarose gel electrophoresis and immunofixation identify a higher percent of monoclonal gammopathies in the elderly than has previously been recognized. Identification of monoclonal components in this population is useful for the subsequent study of plasma cell dyscrasias, neoplastic disease, or other immune dysfunction in the aged.

Authors
Crawford, J; Eye, MK; Cohen, HJ
MLA Citation
Crawford, J, Eye, MK, and Cohen, HJ. "Evaluation of monoclonal gammopathies in the "well" elderly." Am J Med 82.1 (January 1987): 39-45.
PMID
3492143
Source
pubmed
Published In
The American Journal of Medicine
Volume
82
Issue
1
Publish Date
1987
Start Page
39
End Page
45

Influence of donor-specific blood transfusions on host cellular immune responsiveness

Authors
Sanfilippo, F; Crawford, J; Ness, G
MLA Citation
Sanfilippo, F, Crawford, J, and Ness, G. "Influence of donor-specific blood transfusions on host cellular immune responsiveness." Transplantation Proceedings 18.4 (1986): 692-694.
Source
scival
Published In
Transplantation Proceedings
Volume
18
Issue
4
Publish Date
1986
Start Page
692
End Page
694

The essential role of L-glutamine in lymphocyte differentiation in vitro.

The biochemistry of human B lymphocyte differentiation to plasma cells is incompletely understood. L-glutamine appears to be required for both lymphoblastic transformation and plasma cell formation in pokeweed-mitogen-stimulated human peripheral blood mononuclear cell cultures. Cells cultured with pokeweed mitogen in glutamine-deficient RPMI-1640 with 10% heat-inactivated and dialyzed fetal bovine serum were unable to incorporate 3H-thymidine or undergo morphologic lymphoblastic transformation assessed at 72 hours. However, 3H-thymidine incorporation could be maximally restored with as little as 0.08 mM L-glutamine or by using nondialyzed heat-inactivated fetal bovine serum, containing approximately. 1 mM L-glutamine. In subsequent cultures, using glutamine-deficient RPMI-1640 with 10% nondialyzed heat-inactivated fetal bovine serum, lymphoblastic transformation was equivalent with or without additional L-glutamine supplementation. However, only cultures with 2 mM L-glutamine supplementation underwent plasma cell differentiation as assessed by cytoplasmic staining with fluorescein-conjugated anti-immunoglobulin. When the kinetics of cellular immunoglobulin synthesis and secretion were analyzed by 3H- leucine incorporation into immunoglobulin, synthesis was 2-5 fold greater, and secretion 3-10-fold greater in cell cultures with 2 mM L-glutamine supplementation. By electron microscopy, only the glutamine-supplemented cells showed development of rough endoplasmic reticulum consistent with active immunoglobulin production. L-glutamine supplementation had no apparent effect on cell recovery, viability, % B cells, % T cells, % monocytes, or % helper and suppressor T cells. Thus, L-glutamine is essential for both lymphoblastic transformation and plasma cell differentiation. Future investigation of the selective nutritional requirements of cultured cells should yield further insights into the biochemical control of immune cell differentiation and function.

Authors
Crawford, J; Cohen, HJ
MLA Citation
Crawford, J, and Cohen, HJ. "The essential role of L-glutamine in lymphocyte differentiation in vitro." J Cell Physiol 124.2 (August 1985): 275-282.
PMID
4044655
Source
pubmed
Published In
Journal of Cellular Physiology
Volume
124
Issue
2
Publish Date
1985
Start Page
275
End Page
282
DOI
10.1002/jcp.1041240216

Evaluation of hyperviscosity in monoclonal gammopathies.

The serum or plasma hyperviscosity syndrome has been described in both monoclonal and polyclonal immunoglobulin disorders. The usefulness of initial and serial plasma viscosity measurements by an automated viscometer technique was evaluated and compared with serum protein electrophoresis data in 107 patients without monoclonal gammopathies and 153 patients with monoclonal gammopathies. In patients without monoclonal gammopathies, plasma viscosity correlated best with the concentration of gamma globulins. In patients with monoclonal gammopathies, plasma viscosity correlated best with the serum monoclonal protein concentration, but individual patient variations in the ratio of plasma viscosity to monoclonal protein concentration made accurate prediction of plasma viscosity difficult without direct measurement. Six of eight patients with plasma viscosity above 5.0 cp had classic symptoms of hyperviscosity syndrome, and four of the six had recurrent episodes. Six other patients with plasma viscosity above 4.0 cp had more subtle presentations of hyperviscosity but responded equally well to therapeutic lowering of plasma viscosity. These patients are part of a larger subset of 27 patients in whom initial plasma viscosity was above 3.0 cp. No patient with an initial plasma viscosity below 3.0 cp subsequently showed hyperviscosity symptoms. Plasma viscosity measured by this technique is a useful tool in screening patients with dysproteinemias to identify and monitor those with and at risk for the hyperviscosity syndrome.

Authors
Crawford, J; Cox, EB; Cohen, HJ
MLA Citation
Crawford, J, Cox, EB, and Cohen, HJ. "Evaluation of hyperviscosity in monoclonal gammopathies." Am J Med 79.1 (July 1985): 13-22.
PMID
4014299
Source
pubmed
Published In
The American Journal of Medicine
Volume
79
Issue
1
Publish Date
1985
Start Page
13
End Page
22

Aging and neoplasia.

Authors
Crawford, J; Cohen, HJ
MLA Citation
Crawford, J, and Cohen, HJ. "Aging and neoplasia." Annu Rev Gerontol Geriatr 4 (1984): 3-32. (Review)
PMID
6443553
Source
pubmed
Published In
Annual Review of Gerontology and Geriatrics
Volume
4
Publish Date
1984
Start Page
3
End Page
32

An approach to monoclonal gammopathies in the elderly.

Authors
Crawford, J; Cohen, HJ
MLA Citation
Crawford, J, and Cohen, HJ. "An approach to monoclonal gammopathies in the elderly." Geriatrics 37.10 (October 1982): 97-112.
PMID
7117845
Source
pubmed
Published In
Geriatrics
Volume
37
Issue
10
Publish Date
1982
Start Page
97
End Page
112
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