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Halabi, Susan

Overview:

Design and analysis of clinical trials, statistical analysis of biomarker and high dimensional data, development and validation of prognostic and predictive models.

Positions:

Professor of Biostatistics and Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1994

Ph.D. — University of Texas Health Sciences Center at Houston

News:

Grants:

Translational Research in Surgical Oncology

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
January 01, 2002
End Date
August 31, 2021

Health Disparity in African Americans: A Meta-analysis of Six Phase III Trials in Metastatic Castration-Resistant Prosta

Administered By
Biostatistics & Bioinformatics
AwardedBy
Department of Defense
Role
Principal Investigator
Start Date
September 30, 2015
End Date
September 29, 2018

PCRP Clinical Consortium: Duke University Clinical Research Site

Administered By
Medicine, Medical Oncology
AwardedBy
Department of Defense
Role
Statistician
Start Date
March 01, 2007
End Date
September 29, 2017

Validation of prognostic and pathway signatures in lethal prostate cancer

Administered By
Biostatistics & Bioinformatics
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 26, 2011
End Date
August 31, 2017

Development of Circulating Molecular Predictors of Chemotherapy and Novel Hormonal Therapy Benefit in Men with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Administered By
Medicine, Medical Oncology
AwardedBy
Prostate Cancer Foundation
Role
Investigator
Start Date
August 01, 2014
End Date
August 01, 2017

Serum Androgens and Survival in CRPC

Administered By
Duke Cancer Institute
AwardedBy
University of California - San Francisco
Role
Principal Investigator
Start Date
July 01, 2015
End Date
April 30, 2017

Admin Suppl to Study Mechanisms of Ca Sensitivity and Resistance... CALGB 90203

Administered By
Duke Cancer Institute
AwardedBy
Brigham and Women's Hospital
Role
Principal Investigator
Start Date
March 01, 2016
End Date
February 28, 2017

National Clinical Trials Network - Network Group Statistics and DMCs

Administered By
Duke Cancer Institute
AwardedBy
Mayo Clinic
Role
Statistician
Start Date
April 17, 2014
End Date
February 28, 2017

Optimizing First Line Treatment for Men with Castrate Resistant Prostate Cancer

Administered By
Duke Cancer Institute
AwardedBy
Prostate Cancer Foundation
Role
Principal Investigator
Start Date
February 16, 2015
End Date
February 16, 2017

Prognostic Models of Clinical Outcomes In Men With Castration Resistant Prostate Cancer

Administered By
Biostatistics & Bioinformatics
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 06, 2011
End Date
May 31, 2016

Expression Profiling of Renal Cell Carcinoma Utilizing Tissue from CALGB 90206

Administered By
Duke Cancer Institute
AwardedBy
Cedars Sinai Medical Center
Role
Principal Investigator
Start Date
September 12, 2012
End Date
June 30, 2015

Predictive Markers in Metastatic Renal Cancer

Administered By
Duke Cancer Institute
AwardedBy
University of California - San Francisco
Role
Principal Investigator
Start Date
June 01, 2013
End Date
May 31, 2014

Cancer and Leukemia Group B Statistical Center

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
December 01, 1982
End Date
September 30, 2010

Telomerase RNA Transfected Dendritic Cell Vaccines

Administered By
Surgery, Urology
AwardedBy
National Institutes of Health
Role
Statistician
Start Date
July 10, 2002
End Date
June 30, 2006
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Awards:

ASA Fellows. . American Statistical Association.

Type
National
Awarded By
American Statistical Association
Date
January 01, 2015

Fellow. Society of Clinical Trials.

Type
National
Awarded By
Society of Clinical Trials
Date
January 01, 2014

Publications:

A simple method for deriving the confidence regions for the penalized Cox’s model via the minimand perturbation

Authors
Lin, C-Y; Halabi, S
MLA Citation
Lin, C-Y, and Halabi, S. "A simple method for deriving the confidence regions for the penalized Cox’s model via the minimand perturbation (Published online)." Communications in Statistics - Theory and Methods 46.10 (May 19, 2017): 4791-4808.
Source
crossref
Published In
Communication in Statistics Part A - Theory & Methods
Volume
46
Issue
10
Publish Date
2017
Start Page
4791
End Page
4808
DOI
10.1080/03610926.2015.1085568

Phase Ib Trial of Cabazitaxel and Tasquinimod in Men With Heavily Pretreated Metastatic Castration Resistant Prostate Cancer (mCRPC): The CATCH Trial

Authors
Armstrong, AJ; Humeniuk, MS; Healy, P; Szmulewitz, R; Winters, C; Kephart, J; Harrison, MR; Martinez, E; Mundy, K; Halabi, S; George, D
MLA Citation
Armstrong, AJ, Humeniuk, MS, Healy, P, Szmulewitz, R, Winters, C, Kephart, J, Harrison, MR, Martinez, E, Mundy, K, Halabi, S, and George, D. "Phase Ib Trial of Cabazitaxel and Tasquinimod in Men With Heavily Pretreated Metastatic Castration Resistant Prostate Cancer (mCRPC): The CATCH Trial." PROSTATE 77.4 (March 1, 2017): 385-395.
Source
wos-lite
Published In
The Prostate
Volume
77
Issue
4
Publish Date
2017
Start Page
385
End Page
395
DOI
10.1002/pros.23277

Phase Ib Trial of Cabazitaxel and Tasquinimod in Men With Heavily Pretreated Metastatic Castration Resistant Prostate Cancer (mCRPC): The CATCH Trial.

Tasquinimod is an immunomodulating and anti-antiangiogenic oral agent with anti-prostate cancer activity in preclinical studies and in clinical trials of men with metastatic castration resistant prostate cancer (mCRPC), including single agent activity and in combination with taxanes. We sought to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of tasquinimod in combination with cabazitaxel and prednisone in men with chemorefractory mCRPC.Men with mCRPC who had failed prior docetaxel chemotherapy received cabazitaxel 25 mg/m2 every 3 weeks with oral tasquinimod at 1 of 3 escalating dose levels (0.25, 0.5, and 1.0 mg once daily) with prednisone and PEG-filgastrim support, using a 3 + 3 dose escalation design. Treatment continued until progressive disease or unacceptable toxicity.We enrolled 25 men with chemorefractory mCRPC. The RP2D was 0.5 mg tasquinimod based on excess DLTs (two of three men) observed at dose level 3 (1.0 mg) including grade 3 sensory neuropathy and grade 3 atrial fibrillation. Dose level 2 was expanded to 14 men, where 3 DLTs were observed: grade 3 fatigue, grade 4 febrile neutropenia, and grade 3 liver function abnormalities. The proportion of men with a ≥30% PSA decline was 63% and the median composite progression-free survival (PFS) was 8.5 months (95% CI 4.2-16.4 months) based on 12 PFS events. The median number of cycles of cabazitaxel was 6 (range 1-13), with six men receiving >10 cycles. Best overall RECIST responses (CR + PR) were observed in three men (12%), with stable disease in 12 (48%). No pharmacokinetic interactions were observed.We determined the RP2D of tasquinimod combined with cabazitaxel to be 0.5 mg daily following a 3 week lead-in of tasquinimod 0.25 mg with growth factor support. No unexpected toxicities occurred. Prostate 77: 385-395, 2017. © 2016 Wiley Periodicals, Inc.

Authors
Armstrong, AJ; Humeniuk, MS; Healy, P; Szmulewitz, R; Winters, C; Kephart, J; Harrison, MR; Martinez, E; Mundy, K; Halabi, S; George, D
MLA Citation
Armstrong, AJ, Humeniuk, MS, Healy, P, Szmulewitz, R, Winters, C, Kephart, J, Harrison, MR, Martinez, E, Mundy, K, Halabi, S, and George, D. "Phase Ib Trial of Cabazitaxel and Tasquinimod in Men With Heavily Pretreated Metastatic Castration Resistant Prostate Cancer (mCRPC): The CATCH Trial." March 2017.
PMID
27862097
Source
epmc
Published In
The Prostate
Volume
77
Issue
4
Publish Date
2017
Start Page
385
End Page
395
DOI
10.1002/pros.23277

Comparison of futility monitoring guidelines using completed phase III oncology trials.

Futility (inefficacy) interim monitoring is an important component in the conduct of phase III clinical trials, especially in life-threatening diseases. Desirable futility monitoring guidelines allow timely stopping if the new therapy is harmful or if it is unlikely to demonstrate to be sufficiently effective if the trial were to continue to its final analysis. There are a number of analytical approaches that are used to construct futility monitoring boundaries. The most common approaches are based on conditional power, sequential testing of the alternative hypothesis, or sequential confidence intervals. The resulting futility boundaries vary considerably with respect to the level of evidence required for recommending stopping the study.We evaluate the performance of commonly used methods using event histories from completed phase III clinical trials of the Radiation Therapy Oncology Group, Cancer and Leukemia Group B, and North Central Cancer Treatment Group.We considered published superiority phase III trials with survival endpoints initiated after 1990. There are 52 studies available for this analysis from different disease sites. Total sample size and maximum number of events (statistical information) for each study were calculated using protocol-specified effect size, type I and type II error rates. In addition to the common futility approaches, we considered a recently proposed linear inefficacy boundary approach with an early harm look followed by several lack-of-efficacy analyses. For each futility approach, interim test statistics were generated for three schedules with different analysis frequency, and early stopping was recommended if the interim result crossed a futility stopping boundary. For trials not demonstrating superiority, the impact of each rule is summarized as savings on sample size, study duration, and information time scales.For negative studies, our results show that the futility approaches based on testing the alternative hypothesis and repeated confidence interval rules yielded less savings (compared to the other two rules). These boundaries are too conservative, especially during the first half of the study (<50% of information). The conditional power rules are too aggressive during the second half of the study (>50% of information) and may stop a trial even when there is a clinically meaningful treatment effect. The linear inefficacy boundary with three or more interim analyses provided the best results. For positive studies, we demonstrated that none of the futility rules would have stopped the trials.The linear inefficacy boundary futility approach is attractive from statistical, clinical, and logistical standpoints in clinical trials evaluating new anti-cancer agents.

Authors
Zhang, Q; Freidlin, B; Korn, EL; Halabi, S; Mandrekar, S; Dignam, JJ
MLA Citation
Zhang, Q, Freidlin, B, Korn, EL, Halabi, S, Mandrekar, S, and Dignam, JJ. "Comparison of futility monitoring guidelines using completed phase III oncology trials." Clinical trials (London, England) 14.1 (February 2017): 48-58.
PMID
27590208
Source
epmc
Published In
Clinical Trials
Volume
14
Issue
1
Publish Date
2017
Start Page
48
End Page
58
DOI
10.1177/1740774516666502

Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.

Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Patients and Methods Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria. Patients were randomly assigned at a one-to-one ratio to cabozantinib (60 mg once per day) or sunitinib (50 mg once per day; 4 weeks on, 2 weeks off). Progression-free survival (PFS) was the primary end point. Objective response rate (ORR), overall survival, and safety were secondary end points. Results From July 2013 to April 2015, 157 patients were randomly assigned (cabozantinib, n = 79; sunitinib, n = 78). Compared with sunitinib, cabozantinib treatment significantly increased median PFS (8.2 v 5.6 months) and was associated with a 34% reduction in rate of progression or death (adjusted hazard ratio, 0.66; 95% CI, 0.46 to 0.95; one-sided P = .012). ORR was 46% (95% CI, 34 to 57) for cabozantinib versus 18% (95% CI, 10 to 28) for sunitinib. All-causality grade 3 or 4 adverse events were 67% for cabozantinib and 68% for sunitinib and included diarrhea (cabozantinib, 10% v sunitinib, 11%), fatigue (6% v 15%), hypertension (28% v 22%), palmar-plantar erythrodysesthesia (8% v 4%), and hematologic adverse events (3% v 22%). Conclusion Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over standard-of-care sunitinib as first-line therapy in patients with intermediate- or poor-risk mRCC.

Authors
Choueiri, TK; Halabi, S; Sanford, BL; Hahn, O; Michaelson, MD; Walsh, MK; Feldman, DR; Olencki, T; Picus, J; Small, EJ; Dakhil, S; George, DJ; Morris, MJ
MLA Citation
Choueiri, TK, Halabi, S, Sanford, BL, Hahn, O, Michaelson, MD, Walsh, MK, Feldman, DR, Olencki, T, Picus, J, Small, EJ, Dakhil, S, George, DJ, and Morris, MJ. "Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35.6 (February 2017): 591-597.
PMID
28199818
Source
epmc
Published In
Journal of Clinical Oncology
Volume
35
Issue
6
Publish Date
2017
Start Page
591
End Page
597
DOI
10.1200/jco.2016.70.7398

Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy.

Discovery of SNPs that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy.A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy.A total of 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1,000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. An SNP in VAC14 (rs875858) surpassed genome-wide significance (P = 2.12 × 10-8, adjusted P = 5.88 × 10-7). siRNA knockdown of VAC14 in stem cell-derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (P = 0.0015) and branches (P < 0.0001). Prior to docetaxel treatment, VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (P = 0.001).VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization. Clin Cancer Res; 22(19); 4890-900. ©2016 AACR.

Authors
Hertz, DL; Owzar, K; Lessans, S; Wing, C; Jiang, C; Kelly, WK; Patel, J; Halabi, S; Furukawa, Y; Wheeler, HE; Sibley, AB; Lassiter, C; Weisman, L; Watson, D; Krens, SD; Mulkey, F; Renn, CL; Small, EJ; Febbo, PG; Shterev, I; Kroetz, DL; Friedman, PN; Mahoney, JF; Carducci, MA; Kelley, MJ; Nakamura, Y; Kubo, M; Dorsey, SG; Dolan, ME; Morris, MJ; Ratain, MJ; McLeod, HL
MLA Citation
Hertz, DL, Owzar, K, Lessans, S, Wing, C, Jiang, C, Kelly, WK, Patel, J, Halabi, S, Furukawa, Y, Wheeler, HE, Sibley, AB, Lassiter, C, Weisman, L, Watson, D, Krens, SD, Mulkey, F, Renn, CL, Small, EJ, Febbo, PG, Shterev, I, Kroetz, DL, Friedman, PN, Mahoney, JF, Carducci, MA, Kelley, MJ, Nakamura, Y, Kubo, M, Dorsey, SG, Dolan, ME, Morris, MJ, Ratain, MJ, and McLeod, HL. "Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy." Clinical cancer research : an official journal of the American Association for Cancer Research 22.19 (October 2016): 4890-4900.
PMID
27143689
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
22
Issue
19
Publish Date
2016
Start Page
4890
End Page
4900
DOI
10.1158/1078-0432.ccr-15-2823

American Joint Committee on Cancer acceptance criteria for inclusion of risk models for individualized prognosis in the practice of precision medicine.

The American Joint Committee on Cancer (AJCC) has increasingly recognized the need for more personalized probabilistic predictions than those delivered by ordinal staging systems, particularly through the use of accurate risk models or calculators. However, judging the quality and acceptability of a risk model is complex. The AJCC Precision Medicine Core conducted a 2-day meeting to discuss characteristics necessary for a quality risk model in cancer patients. More specifically, the committee established inclusion and exclusion criteria necessary for a risk model to potentially be endorsed by the AJCC. This committee reviewed and discussed relevant literature before creating a checklist unique to this need of AJCC risk model endorsement. The committee identified 13 inclusion and 3 exclusion criteria for AJCC risk model endorsement in cancer. The emphasis centered on performance metrics, implementation clarity, and clinical relevance. The facilitation of personalized probabilistic predictions for cancer patients holds tremendous promise, and these criteria will hopefully greatly accelerate this process. Moreover, these criteria might be useful for a general audience when trying to judge the potential applicability of a published risk model in any clinical domain. CA Cancer J Clin 2016;66:370-374. © 2016 American Cancer Society.

Authors
Kattan, MW; Hess, KR; Amin, MB; Lu, Y; Moons, KGM; Gershenwald, JE; Gimotty, PA; Guinney, JH; Halabi, S; Lazar, AJ; Mahar, AL; Patel, T; Sargent, DJ; Weiser, MR; Compton, C
MLA Citation
Kattan, MW, Hess, KR, Amin, MB, Lu, Y, Moons, KGM, Gershenwald, JE, Gimotty, PA, Guinney, JH, Halabi, S, Lazar, AJ, Mahar, AL, Patel, T, Sargent, DJ, Weiser, MR, and Compton, C. "American Joint Committee on Cancer acceptance criteria for inclusion of risk models for individualized prognosis in the practice of precision medicine." CA: a cancer journal for clinicians 66.5 (September 2016): 370-374.
PMID
26784705
Source
epmc
Published In
Ca: A Cancer Journal for Clinicians
Volume
66
Issue
5
Publish Date
2016
Start Page
370
End Page
374
DOI
10.3322/caac.21339

Critical Assessment of Clinical Prognostic Tools in Melanoma.

The 7th edition American Joint Committee on Cancer (AJCC) melanoma staging system classifies patients according to prognosis. Significant within-stage heterogeneity remains and the inclusion of additional clinicopathologic and other host- and tumor-based prognostic factors have been proposed. Clinical prognostic tools have been developed for use in clinical practice to refine survival estimates. Little is known about the comparative features of tools in melanoma. We performed a systematic search of the scientific published literature for clinical prognostic tools in melanoma and web-based resources. A priori criteria were used to evaluate their quality and clinical relevance, and included intended clinical use, model development approaches, validation strategies, and performance metrics. We identified 17 clinical prognostic tools for primary cutaneous melanoma. Patients with stages I-III and T1 or thin melanoma were the most frequently considered populations. Seventy-five percent of tools were developed using data collected from patients diagnosed in 2006 or earlier, and the well-established factors of tumor thickness, ulceration, and age were included in 70 % of tools. Internal validity using cross-validation or bootstrapping techniques was performed for two tools only. Fewer than half were evaluated for external validity; however, when done, the appropriate statistical methodology was applied and results indicated good generalizability. Several clinical prognostic tools have the potential to refine survival estimates for individual melanoma patients; however, there is a great opportunity to improve these tools and to foster the development of new, validated tools by the inclusion of contemporary clinicopathological covariates and by using improved statistical and methodological approaches.

Authors
Mahar, AL; Compton, C; Halabi, S; Hess, KR; Gershenwald, JE; Scolyer, RA; Groome, PA
MLA Citation
Mahar, AL, Compton, C, Halabi, S, Hess, KR, Gershenwald, JE, Scolyer, RA, and Groome, PA. "Critical Assessment of Clinical Prognostic Tools in Melanoma." Annals of surgical oncology 23.9 (September 2016): 2753-2761.
PMID
27052645
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
9
Publish Date
2016
Start Page
2753
End Page
2761
DOI
10.1245/s10434-016-5212-5

Residential metal contamination and potential health risks of exposure in adobe brick houses in Potosí, Bolivia.

Potosí, Bolivia, is the site of centuries of historic and present-day mining of the Cerro Rico, a mountain known for its rich polymetallic deposits, and was the site of large-scale Colonial era silver refining operations. In this study, the concentrations of several metal and metalloid elements were quantified in adobe brick, dirt floor, and surface dust samples from 49 houses in Potosí. Median concentrations of total mercury (Hg), lead (Pb), and arsenic (As) were significantly greater than concentrations measured in Sucre, Bolivia, a non-mining town, and exceeded US-based soil screening levels. Adobe brick samples were further analyzed for bioaccessible concentrations of trace elements using a simulated gastric fluid (GF) extraction. Median GF extractable concentrations of Hg, As, and Pb were 0.085, 13.9, and 32.2% of the total element concentration, respectively. Total and GF extractable concentrations of Hg, As, and Pb were used to estimate exposure and potential health risks to children following incidental ingestion of adobe brick particles. Risks were assessed using a range of potential ingestion rates (50-1000mg/day). Overall, the results of the risk assessment show that the majority of households sampled contained concentrations of bioaccessible Pb and As, but not Hg, that represent a potential health risk. Even at the lowest ingestion rate considered, the majority of households exceeded the risk threshold for Pb, indicating that the concentrations of this metal are of particular concern. To our knowledge, this is the first study to quantify key trace elements in building materials in adobe brick houses and the results indicate that these houses are a potential source of exposure to metals and metalloids in South American mining communities. Additional studies are needed to fully characterize personal exposure and to understand potential adverse health outcomes within the community.

Authors
McEwen, AR; Hsu-Kim, H; Robins, NA; Hagan, NA; Halabi, S; Barras, O; Richter, DD; Vandenberg, JJ
MLA Citation
McEwen, AR, Hsu-Kim, H, Robins, NA, Hagan, NA, Halabi, S, Barras, O, Richter, DD, and Vandenberg, JJ. "Residential metal contamination and potential health risks of exposure in adobe brick houses in Potosí, Bolivia." The Science of the total environment 562 (August 2016): 237-246.
PMID
27100004
Source
epmc
Published In
Science of the Total Environment
Volume
562
Publish Date
2016
Start Page
237
End Page
246
DOI
10.1016/j.scitotenv.2016.03.152

Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer.

Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials.Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases.Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although men with lung metastases had better median OS (19.4 months) compared with men with liver metastases, they had significantly worse median survival duration than men with nonvisceral bone metastases (21.3 months). Men with LN-only disease had a median OS of 31.6 months. The pooled hazard ratios for death in men with lung metastases compared with men with bone with or without LN metastases and in men with any liver metastases compared with men with lung metastases were 1.14 (95% CI, 1.04 to 1.25; P = .007) and 1.52 (95% CI, 1.35 to 1.73; P < .0001), respectively.Specific sites of metastases in men with mCRPC are associated with differential OS, with successive increased lethality for lung and liver metastases compared with bone and nonvisceral involvement. These data may help in treatment decisions, the design of future clinical trials, and understanding the variation in biology of different sites of metastases in men with mCRPC.

Authors
Halabi, S; Kelly, WK; Ma, H; Zhou, H; Solomon, NC; Fizazi, K; Tangen, CM; Rosenthal, M; Petrylak, DP; Hussain, M; Vogelzang, NJ; Thompson, IM; Chi, KN; de Bono, J; Armstrong, AJ; Eisenberger, MA; Fandi, A; Li, S; Araujo, JC; Logothetis, CJ; Quinn, DI; Morris, MJ; Higano, CS; Tannock, IF; Small, EJ
MLA Citation
Halabi, S, Kelly, WK, Ma, H, Zhou, H, Solomon, NC, Fizazi, K, Tangen, CM, Rosenthal, M, Petrylak, DP, Hussain, M, Vogelzang, NJ, Thompson, IM, Chi, KN, de Bono, J, Armstrong, AJ, Eisenberger, MA, Fandi, A, Li, S, Araujo, JC, Logothetis, CJ, Quinn, DI, Morris, MJ, Higano, CS, Tannock, IF, and Small, EJ. "Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.14 (May 2016): 1652-1659.
PMID
26951312
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
14
Publish Date
2016
Start Page
1652
End Page
1659
DOI
10.1200/jco.2015.65.7270

Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3.

Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials.PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval.

Authors
Scher, HI; Morris, MJ; Stadler, WM; Higano, C; Basch, E; Fizazi, K; Antonarakis, ES; Beer, TM; Carducci, MA; Chi, KN; Corn, PG; de Bono, JS; Dreicer, R; George, DJ; Heath, EI; Hussain, M; Kelly, WK; Liu, G; Logothetis, C; Nanus, D; Stein, MN; Rathkopf, DE; Slovin, SF; Ryan, CJ; Sartor, O; Small, EJ; Smith, MR; Sternberg, CN; Taplin, M-E; Wilding, G; Nelson, PS; Schwartz, LH; Halabi, S; Kantoff, PW; Armstrong, AJ
MLA Citation
Scher, HI, Morris, MJ, Stadler, WM, Higano, C, Basch, E, Fizazi, K, Antonarakis, ES, Beer, TM, Carducci, MA, Chi, KN, Corn, PG, de Bono, JS, Dreicer, R, George, DJ, Heath, EI, Hussain, M, Kelly, WK, Liu, G, Logothetis, C, Nanus, D, Stein, MN, Rathkopf, DE, Slovin, SF, Ryan, CJ, Sartor, O, Small, EJ, Smith, MR, Sternberg, CN, Taplin, M-E, Wilding, G, Nelson, PS, Schwartz, LH, Halabi, S, Kantoff, PW, and Armstrong, AJ. "Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.12 (April 2016): 1402-1418.
PMID
26903579
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
12
Publish Date
2016
Start Page
1402
End Page
1418
DOI
10.1200/jco.2015.64.2702

Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.

Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery.Men with localized PC treated with radical prostatectomy at the Durham VA Medical Center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1 and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics an risk of PSA recurrence over time.Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; three died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N-cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence or Gleason sum were noted for SNAIL, ZEB1, vimentin or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (P=0.043), National Comprehensive Cancer Network risk (P=0.013) and PSA recurrence (hazard ratio 1.07, P=0.016).The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery.

Authors
Armstrong, AJ; Healy, P; Halabi, S; Vollmer, R; Lark, A; Kemeny, G; Ware, K; Freedland, SJ
MLA Citation
Armstrong, AJ, Healy, P, Halabi, S, Vollmer, R, Lark, A, Kemeny, G, Ware, K, and Freedland, SJ. "Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer." Prostate cancer and prostatic diseases 19.1 (March 2016): 40-45.
Website
http://hdl.handle.net/10161/10917
PMID
26458958
Source
epmc
Published In
Prostate Cancer and Prostatic Diseases
Volume
19
Issue
1
Publish Date
2016
Start Page
40
End Page
45
DOI
10.1038/pcan.2015.46

Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial.

Non-clear cell renal cell carcinomas are histologically and genetically diverse kidney cancers with variable prognoses, and their optimum initial treatment is unknown. We aimed to compare the mTOR inhibitor everolimus and the VEGF receptor inhibitor sunitinib in patients with non-clear cell renal cell carcinoma.We enrolled patients with metastatic papillary, chromophobe, or unclassified non-clear cell renal cell carcinoma with no history of previous systemic treatment. Patients were randomly assigned (1:1) to receive everolimus (10 mg/day) or sunitinib (50 mg/day; 6-week cycles of 4 weeks with treatment followed by 2 weeks without treatment) administered orally until disease progression or unacceptable toxicity. Randomisation was stratified by Memorial Sloan Kettering Cancer Center risk group and papillary histology. The primary endpoint was progression-free survival in the intention-to-treat population using the RECIST 1.1 criteria. Safety was assessed in all patients who were randomly assigned to treatment. This study is registered with ClinicalTrials.gov, number NCT01108445.Between Sept 23, 2010, and Oct 28, 2013, 108 patients were randomly assigned to receive either sunitinib (n=51) or everolimus (n=57). As of December, 2014, 87 progression-free survival events had occurred with two remaining active patients, and the trial was closed for the primary analysis. Sunitinib significantly increased progression-free survival compared with everolimus (8·3 months [80% CI 5·8-11·4] vs 5·6 months [5·5-6·0]; hazard ratio 1·41 [80% CI 1·03-1·92]; p=0·16), although heterogeneity of the treatment effect was noted on the basis of histological subtypes and prognostic risk groups. No unexpected toxic effects were reported, and the most common grade 3-4 adverse events were hypertension (12 [24%] of 51 patients in the sunitinib group vs one [2%] of 57 patients in the everolimus group), infection (six [12%] vs four [7%]), diarrhoea (five [10%] vs one [2%]), pneumonitis (none vs five [9%]), stomatitis (none vs five [9%]), and hand-foot syndrome (four [8%] vs none).In patients with metastatic non-clear cell renal cell carcinoma, sunitinib improved progression-free survival compared with everolimus. Future trials of novel agents should account for heterogeneity in disease outcomes based on genetic, histological, and prognostic factors.Novartis and Pfizer.

Authors
Armstrong, AJ; Halabi, S; Eisen, T; Broderick, S; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Hainsworth, JD; Kollmannsberger, CK; Logan, TF; Puzanov, I; Pickering, LM; Ryan, CW; Protheroe, A; Lusk, CM; Oberg, S; George, DJ
MLA Citation
Armstrong, AJ, Halabi, S, Eisen, T, Broderick, S, Stadler, WM, Jones, RJ, Garcia, JA, Vaishampayan, UN, Picus, J, Hawkins, RE, Hainsworth, JD, Kollmannsberger, CK, Logan, TF, Puzanov, I, Pickering, LM, Ryan, CW, Protheroe, A, Lusk, CM, Oberg, S, and George, DJ. "Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial." The Lancet. Oncology 17.3 (March 2016): 378-388.
PMID
26794930
Source
epmc
Published In
The Lancet Oncology
Volume
17
Issue
3
Publish Date
2016
Start Page
378
End Page
388
DOI
10.1016/s1470-2045(15)00515-x

High Dimensional Variable Selection with Error Control.

Background. The iterative sure independence screening (ISIS) is a popular method in selecting important variables while maintaining most of the informative variables relevant to the outcome in high throughput data. However, it not only is computationally intensive but also may cause high false discovery rate (FDR). We propose to use the FDR as a screening method to reduce the high dimension to a lower dimension as well as controlling the FDR with three popular variable selection methods: LASSO, SCAD, and MCP. Method. The three methods with the proposed screenings were applied to prostate cancer data with presence of metastasis as the outcome. Results. Simulations showed that the three variable selection methods with the proposed screenings controlled the predefined FDR and produced high area under the receiver operating characteristic curve (AUROC) scores. In applying these methods to the prostate cancer example, LASSO and MCP selected 12 and 8 genes and produced AUROC scores of 0.746 and 0.764, respectively. Conclusions. We demonstrated that the variable selection methods with the sequential use of FDR and ISIS not only controlled the predefined FDR in the final models but also had relatively high AUROC scores.

Authors
Kim, S; Halabi, S
MLA Citation
Kim, S, and Halabi, S. "High Dimensional Variable Selection with Error Control." BioMed research international 2016 (January 2016): 8209453-.
PMID
27597974
Source
epmc
Published In
BioMed Research International
Volume
2016
Publish Date
2016
Start Page
8209453
DOI
10.1155/2016/8209453

The Development of Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP).

New systemic therapies have prolonged the lives of men with metastatic castration-resistant prostate cancer (mCRPC). Use of these therapies in the adjuvant setting when the disease may be micrometastatic and potentially more sensitive to therapies may decrease mortality from prostate cancer. However, the conduct of adjuvant prostate cancer clinical trials is hampered by taking longer than a decade to reach the meaningful endpoint of overall survival (OS) and the fact that many men never die from prostate cancer, even if they relapse. A validated intermediate clinical endpoint (ICE) in prostate cancer that is a robust surrogate for OS has yet to be defined. This paper details the plans, process, and progress of the international Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group to pool individual patient data from all available clinical trials of radiation or prostatectomy for localized disease and conduct the requisite analyses to determine whether an ICE can be identified. This paper further details the challenges and the a priori statistical analytical plans and strategies to define an ICE for adjuvant prostate cancer clinical trials. In addition, a brief review of the health economic analyses to model the benefits to patients, society and manufacturers is detailed. If successful, the results from this work will provide a robust surrogate for OS that will expedite the design and conduct of future adjuvant therapy trials using new agents that have proven activity in mCRPC. Moreover, it will also define the health economic benefits to patients and societies.

Authors
Sweeney, C; Nakabayashi, M; Regan, M; Xie, W; Hayes, J; Keating, N; Li, S; Philipson, T; Buyse, M; Halabi, S; Kantoff, P; Sartor, AO; Soule, H; Mahal, B
MLA Citation
Sweeney, C, Nakabayashi, M, Regan, M, Xie, W, Hayes, J, Keating, N, Li, S, Philipson, T, Buyse, M, Halabi, S, Kantoff, P, Sartor, AO, Soule, H, and Mahal, B. "The Development of Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP)." Journal of the National Cancer Institute 107.12 (December 2015): djv261-.
PMID
26409187
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
107
Issue
12
Publish Date
2015
Start Page
djv261
DOI
10.1093/jnci/djv261

Refining Prognosis in Lung Cancer: A Report on the Quality and Relevance of Clinical Prognostic Tools.

Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biological, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer.A systematic search of the scientific literature for clinical prognostic tools in lung cancer published from January 1, 1996 to January 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics.Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small-cell lung cancer. All tools for small-cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only 11 were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision points and prioritized inclusion of established prognostic factors over emerging factors.Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation.

Authors
Mahar, AL; Compton, C; McShane, LM; Halabi, S; Asamura, H; Rami-Porta, R; Groome, PA
MLA Citation
Mahar, AL, Compton, C, McShane, LM, Halabi, S, Asamura, H, Rami-Porta, R, and Groome, PA. "Refining Prognosis in Lung Cancer: A Report on the Quality and Relevance of Clinical Prognostic Tools." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 10.11 (November 2015): 1576-1589.
PMID
26313682
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
10
Issue
11
Publish Date
2015
Start Page
1576
End Page
1589
DOI
10.1097/jto.0000000000000652

A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance).

Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely.This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray® platform for TaqMan® RT-qPCR. The dataset was randomly divided at 2:1 ratio into training (n = 221) and testing (n = 103) sets to develop a multigene prognostic signature.Gene expressions were measured in 324 patients. In the training set, multiple models testing 424 candidate genes identified a prognostic signature containing 8 genes plus MSKCC clinical risk factors. In the testing set, the time dependent (td) AUC for a prognostic model containing the 8 genes with and without MSKCC risk factors were 0.72 and 0.69, respectively. The tdAUC for the clinical risk factors alone was 0.61. Additional primary mRCCs from patients with mRCC (n = 12) were sampled in multiple sites and standard deviations of gene expressions within a tumor were used as a measure of heterogeneity. All 8 genes in the final prognostic model met our criteria for minimal heterogeneity.A molecular prognostic signature based on 8 genes was developed and is ready for external validation in this patient population and other related settings such as nonmetastatic RCC.

Authors
Kim, HL; Halabi, S; Li, P; Mayhew, G; Simko, J; Nixon, AB; Small, EJ; Rini, B; Morris, MJ; Taplin, M-E; George, D
MLA Citation
Kim, HL, Halabi, S, Li, P, Mayhew, G, Simko, J, Nixon, AB, Small, EJ, Rini, B, Morris, MJ, Taplin, M-E, and George, D. "A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance)." EBioMedicine 2.11 (November 2015): 1814-1820.
PMID
26870806
Source
epmc
Published In
EBioMedicine
Volume
2
Issue
11
Publish Date
2015
Start Page
1814
End Page
1820
DOI
10.1016/j.ebiom.2015.09.012

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

Authors
Gillessen, S; Omlin, A; Attard, G; de Bono, JS; Efstathiou, E; Fizazi, K; Halabi, S; Nelson, PS; Sartor, O; Smith, MR; Soule, HR; Akaza, H; Beer, TM; Beltran, H; Chinnaiyan, AM; Daugaard, G; Davis, ID; De Santis, M; Drake, CG; Eeles, RA; Fanti, S; Gleave, ME; Heidenreich, A; Hussain, M; James, ND; Lecouvet, FE; Logothetis, CJ; Mastris, K; Nilsson, S; Oh, WK; Olmos, D; Padhani, AR; Parker, C; Rubin, MA; Schalken, JA; Scher, HI; Sella, A; Shore, ND; Small, EJ; Sternberg, CN; Suzuki, H et al.
MLA Citation
Gillessen, S, Omlin, A, Attard, G, de Bono, JS, Efstathiou, E, Fizazi, K, Halabi, S, Nelson, PS, Sartor, O, Smith, MR, Soule, HR, Akaza, H, Beer, TM, Beltran, H, Chinnaiyan, AM, Daugaard, G, Davis, ID, De Santis, M, Drake, CG, Eeles, RA, Fanti, S, Gleave, ME, Heidenreich, A, Hussain, M, James, ND, Lecouvet, FE, Logothetis, CJ, Mastris, K, Nilsson, S, Oh, WK, Olmos, D, Padhani, AR, Parker, C, Rubin, MA, Schalken, JA, Scher, HI, Sella, A, Shore, ND, Small, EJ, Sternberg, CN, and Suzuki, H et al. "Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015." Annals of oncology : official journal of the European Society for Medical Oncology 26.8 (August 2015): 1589-1604.
PMID
26041764
Source
epmc
Published In
Annals of Oncology
Volume
26
Issue
8
Publish Date
2015
Start Page
1589
End Page
1604
DOI
10.1093/annonc/mdv257

A novel test to compare two treatments based on endpoints involving both nonfatal and fatal events.

In a clinical trial comparing two treatment groups, one commonly-used endpoint is time to death. Another is time until the first nonfatal event (if there is one) or until death (if not). Both endpoints have drawbacks. The wrong choice may adversely affect the value of the study by impairing power if deaths are too few (with the first endpoint) or by lessening the role of mortality if not (with the second endpoint). We propose a compromise that provides a simple test based on the time to death if the patient has died or time since randomization augmented by an increment otherwise. The test applies the ordinary two-sample Wilcoxon statistic to these values. The formula for the increment (the same for experimental and control patients) must be specified before the trial starts. In the simplest (and perhaps most useful) case, the increment assumes only two values, according to whether or not the (surviving) patient had a nonfatal event. More generally, the increment depends on the time of the first nonfatal event, if any, and the time since randomization. The test has correct Type I error even though it does not handle censoring in a customary way. For conditions where investigators would face no easy (advance) choice between the two older tests, simulation results favor the new test. An example using a renal-cancer trial is presented.

Authors
Potthoff, RF; Halabi, S
MLA Citation
Potthoff, RF, and Halabi, S. "A novel test to compare two treatments based on endpoints involving both nonfatal and fatal events." Pharmaceutical statistics 14.4 (July 2015): 273-283.
PMID
25894200
Source
epmc
Published In
Pharmaceutical Statistics: the Journal of Applied Statistics in the Pharmaceutical Industry
Volume
14
Issue
4
Publish Date
2015
Start Page
273
End Page
283
DOI
10.1002/pst.1683

Reply to progression-free survival: Does a correlation with survival justify its role as a surrogate clinical endpoint?

Authors
Becker, A; Eichelberg, C; Sun, M
MLA Citation
Becker, A, Eichelberg, C, and Sun, M. "Reply to progression-free survival: Does a correlation with survival justify its role as a surrogate clinical endpoint?." Cancer 121.11 (June 1, 2015): 1906-1907.
Source
crossref
Published In
Cancer
Volume
121
Issue
11
Publish Date
2015
Start Page
1906
End Page
1907
DOI
10.1002/cncr.29255

Mercury hair levels and factors that influence exposure for residents of Huancavelica, Peru.

Between 1564 and 1810, nearly 17,000 metric tons of mercury (Hg) vapor was released to the environment during cinnabar refining in the small town of Huancavelica, Peru. The present study characterizes individual exposure to mercury using total and speciated Hg from residential samples, total Hg in hair, and self-reported questionnaire data regarding factors influencing exposure (e.g., frequency of fish consumption, occupation). Total Hg concentrations in hair from 118 participants ranged from 0.10 to 3.6 µg/g, similar to concentrations found in the USA and lower than concentrations in other Hg-exposed populations around the world. Pearson's correlation coefficients for data in this study suggest that there is a positive correlation between concentrations of total Hg in hair and concentrations of total Hg in adobe bricks, dirt floors, and surface dust; however, these correlations are not statistically significant. Results of a one-way analysis of variance (ANOVA) identified that total Hg concentrations in hair were significantly related to gender (p < 0.001), living in a neighborhood where smelters were previously located (p = 0.021), smoking status (p = 0.003), frequency of house cleaning (p = 0.019), and frequency of fish consumption (p = 0.046). These results highlight the need for further studies to better characterize Hg exposure in Huancavelica, particularly as related to residential contamination. A comprehensive analysis of residential Hg contamination and exposure in Huancavelica will guide the development and implementation of mitigation and remediation strategies in the community to reduce potential health risks from residential Hg exposure.

Authors
Hagan, N; Robins, N; Hsu-Kim, H; Halabi, S; Espinoza Gonzales, RD; Ecos, E; Richter, D; Vandenberg, J
MLA Citation
Hagan, N, Robins, N, Hsu-Kim, H, Halabi, S, Espinoza Gonzales, RD, Ecos, E, Richter, D, and Vandenberg, J. "Mercury hair levels and factors that influence exposure for residents of Huancavelica, Peru." Environmental geochemistry and health 37.3 (June 2015): 507-514.
PMID
25467206
Source
epmc
Published In
Environmental Geochemistry and Health
Volume
37
Issue
3
Publish Date
2015
Start Page
507
End Page
514
DOI
10.1007/s10653-014-9665-9

Progression-free survival: does a correlation with survival justify its role as a surrogate clinical endpoint?

Authors
Halabi, S; Rini, BI; Escudier, B; Stadler, WM; Small, EJ
MLA Citation
Halabi, S, Rini, BI, Escudier, B, Stadler, WM, and Small, EJ. "Progression-free survival: does a correlation with survival justify its role as a surrogate clinical endpoint?." Cancer 121.11 (June 2015): 1906-.
PMID
25677867
Source
epmc
Published In
Cancer
Volume
121
Issue
11
Publish Date
2015
Start Page
1906
DOI
10.1002/cncr.29252

Final clinical results of a randomized phase II international trial of everolimus vs. sunitinib in patients with metastatic non-clear cell renal cell carcinoma (ASPEN)

Authors
Armstrong, AJ; Broderick, S; Eisen, T; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Hainsworth, JD; Kollmannsberger, CK; Logan, TF; Puzanov, I; Pickering, LM; Ryan, CW; Protheroe, A; Lusk, CM; Oberg, S; Halabi, S; George, DJ
MLA Citation
Armstrong, AJ, Broderick, S, Eisen, T, Stadler, WM, Jones, RJ, Garcia, JA, Vaishampayan, UN, Picus, J, Hawkins, RE, Hainsworth, JD, Kollmannsberger, CK, Logan, TF, Puzanov, I, Pickering, LM, Ryan, CW, Protheroe, A, Lusk, CM, Oberg, S, Halabi, S, and George, DJ. "Final clinical results of a randomized phase II international trial of everolimus vs. sunitinib in patients with metastatic non-clear cell renal cell carcinoma (ASPEN)." May 20, 2015.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
33
Issue
15
Publish Date
2015

Bevacizumab and the risk of arterial and venous thromboembolism in patients with metastatic, castration-resistant prostate cancer treated on Cancer and Leukemia Group B (CALGB) 90401 (Alliance).

Bevacizumab is associated with an increased risk of arterial thromboembolism (ATE); however, its effect on venous thromboembolism (VTE) remains controversial. Scant data exist on the factors that increase the risk of ATE/VTE in patients with prostate cancer. The authors investigated the association of bevacizumab treatment and clinical factors with ATE/VTE risk in patients who were treated on Cancer and Leukemia Group B (CALGB) trial 90401.Patients with metastatic, castration-resistant prostate cancer were randomized to receive docetaxel and prednisone with or without bevacizumab once every 21 days. Cycle-to-event Cox regression models were used to investigate the association of bevacizumab with the incidence of grade 3 or greater (≥ 3) ATE and VTE. Age, prior ATE/VTE, baseline antiplatelet/anticoagulant use, and VTE risk score (based on leukocyte count, hemoglobin, platelet count, body mass index, and tumor location) were evaluated in univariate and multivariable analyses.Of 1008 randomized patients, the odds of experiencing grade ≥ 3 ATE were significantly greater in those who received bevacizumab compared with those who received placebo (odds ratio, 2.79; P = .02), whereas an opposite trend was noted for grade ≥ 3 VTE (odds ratio, 0.60; P = .08). In the multivariable analysis, bevacizumab treatment (hazard ratio [HR], 3.00; P = .01) and age (HR, 1.06; P = .02) were significantly associated with the risk of ATE; whereas age (HR, 1.05; P = .01) and VTE risk score (HR, 1.83; P = .03) were significantly associated with the risk of VTE.Bevacizumab was significantly associated with a greater risk of ATE in patients with metastatic, castration-resistant prostate cancer, but it was not significantly associated with the risk of VTE. Understanding clinical factors that increase the risk for experiencing ATE/VTE is essential to mitigate the risks and reduce the burden of these prevalent complications in cancer care.

Authors
Patel, JN; Jiang, C; Hertz, DL; Mulkey, FA; Owzar, K; Halabi, S; Ratain, MJ; Friedman, PN; Small, EJ; Carducci, MA; Mahoney, JF; Kelley, MJ; Morris, MJ; Kelly, WK; McLeod, HL
MLA Citation
Patel, JN, Jiang, C, Hertz, DL, Mulkey, FA, Owzar, K, Halabi, S, Ratain, MJ, Friedman, PN, Small, EJ, Carducci, MA, Mahoney, JF, Kelley, MJ, Morris, MJ, Kelly, WK, and McLeod, HL. "Bevacizumab and the risk of arterial and venous thromboembolism in patients with metastatic, castration-resistant prostate cancer treated on Cancer and Leukemia Group B (CALGB) 90401 (Alliance)." Cancer 121.7 (April 2015): 1025-1031.
PMID
25417775
Source
epmc
Published In
Cancer
Volume
121
Issue
7
Publish Date
2015
Start Page
1025
End Page
1031
DOI
10.1002/cncr.29169

Making progress on progression in metastatic prostate cancer.

Authors
Armstrong, AJ; Halabi, S
MLA Citation
Armstrong, AJ, and Halabi, S. "Making progress on progression in metastatic prostate cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33.12 (April 2015): 1322-1324.
PMID
25667271
Source
epmc
Published In
Journal of Clinical Oncology
Volume
33
Issue
12
Publish Date
2015
Start Page
1322
End Page
1324
DOI
10.1200/jco.2014.59.4283

Clinical phenotypes associated with circulating tumor cell enumeration in metastatic castration-resistant prostate cancer

© 2015 Elsevier Inc.Background: The presence of ≥5 circulating tumor cells (CTCs) is prognostic for shorter survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, some men have low CTCs despite widespread disease, suggesting heterogeneity in CTC phenotype or detection. The aim of this study was to evaluate the association of CTC enumeration with clinical disease characteristics and overall survival in men with mCRPC at our institution. Design: CTCs were enumerated using the CellSearch method in a prospective correlative study in men with mCRPC starting a new systemic therapy. The primary objective was to determine the clinical phenotype of the subset of men with mCRPC who have a poor prognosis and low CTCs. Secondary end points included associations of CTCs with survival and known prognostic biomarkers, before therapy and at progression. Results: At baseline, median CTC count was 16 cells and prostate-specific antigen (PSA) level was 178. ng/ml. At progression, median CTC count was 42, PSA level was 245. ng/ml, levels of lactate dehydrogenase and alkaline phosphatase rose, and level of hemoglobin dropped. The median overall survival for this heavily pretreated population was 11.2 months, and the multivariable hazard ratio for death of men with CTCs<5 vs.≥5 was 0.43 (95% CI: 0.24-0.77). Median progression-free survival was 4.4 months. CTC enumeration modestly correlated with lactate dehydrogenase and alkaline phosphatase levels but only weakly correlated with PSA and hemoglobin levels. We were unable to identify a consistent subgroup of poor prognosis men with a low number of CTCs. Conclusion: CTC enumeration appears to be prognostic in men with mCRPC and describes a phenotype of hematogenous dissemination that cannot be predicted based on standard clinical and laboratory assessments.

Authors
Bitting, RL; Healy, P; Halabi, S; George, DJ; Goodin, M; Armstrong, AJ
MLA Citation
Bitting, RL, Healy, P, Halabi, S, George, DJ, Goodin, M, and Armstrong, AJ. "Clinical phenotypes associated with circulating tumor cell enumeration in metastatic castration-resistant prostate cancer." Urologic Oncology: Seminars and Original Investigations 33.3 (March 1, 2015): 110.e1-110.e9.
Source
scopus
Published In
Urologic Oncology: Seminars and Original Investigations
Volume
33
Issue
3
Publish Date
2015
Start Page
110.e1
End Page
110.e9
DOI
10.1016/j.urolonc.2014.09.002

Clinical phenotypes associated with circulating tumor cell enumeration in metastatic castration-resistant prostate cancer.

The presence of ≥5 circulating tumor cells (CTCs) is prognostic for shorter survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, some men have low CTCs despite widespread disease, suggesting heterogeneity in CTC phenotype or detection. The aim of this study was to evaluate the association of CTC enumeration with clinical disease characteristics and overall survival in men with mCRPC at our institution.CTCs were enumerated using the CellSearch method in a prospective correlative study in men with mCRPC starting a new systemic therapy. The primary objective was to determine the clinical phenotype of the subset of men with mCRPC who have a poor prognosis and low CTCs. Secondary end points included associations of CTCs with survival and known prognostic biomarkers, before therapy and at progression.At baseline, median CTC count was 16 cells and prostate-specific antigen (PSA) level was 178 ng/ml. At progression, median CTC count was 42, PSA level was 245 ng/ml, levels of lactate dehydrogenase and alkaline phosphatase rose, and level of hemoglobin dropped. The median overall survival for this heavily pretreated population was 11.2 months, and the multivariable hazard ratio for death of men with CTCs<5 vs.≥5 was 0.43 (95% CI: 0.24-0.77). Median progression-free survival was 4.4 months. CTC enumeration modestly correlated with lactate dehydrogenase and alkaline phosphatase levels but only weakly correlated with PSA and hemoglobin levels. We were unable to identify a consistent subgroup of poor prognosis men with a low number of CTCs.CTC enumeration appears to be prognostic in men with mCRPC and describes a phenotype of hematogenous dissemination that cannot be predicted based on standard clinical and laboratory assessments.

Authors
Bitting, RL; Healy, P; Halabi, S; George, DJ; Goodin, M; Armstrong, AJ
MLA Citation
Bitting, RL, Healy, P, Halabi, S, George, DJ, Goodin, M, and Armstrong, AJ. "Clinical phenotypes associated with circulating tumor cell enumeration in metastatic castration-resistant prostate cancer." Urologic oncology 33.3 (March 2015): 110.e1-110.e9.
PMID
25595577
Source
epmc
Published In
Urologic Oncology: Seminars and Original Investigations
Volume
33
Issue
3
Publish Date
2015
Start Page
110.e1
End Page
110.e9
DOI
10.1016/j.urolonc.2014.09.002

Independent data monitoring committees: an update and overview.

An independent data monitoring committee׳s (IDMC's) duty is to ensure that the interests of the patients entered in the trial are being well served (i.e., the risk-benefit ratio is appropriate) and that the scientific integrity of the trial is maintained during the interim between trial initiation and trial completion. Industry sponsors form IDMCs to ensure an independent assessment to assure that the study participants are not exposed to unnecessary or unreasonable risks because of their trial participation and to ensure that the study is being conducted according to highest scientific and ethical standards. IDMCs are needed to analyze interim data for large randomized studies, in particular those that involve multiple sites and important clinical end points such as survival or disease progression. Ethical principles mandate that clinical trials begin with uncertainty as to which treatment is better (clinical equipoise). This uncertainty should be maintained during study conduct and analysis unless there are compelling data that emerge during the conduct of the trial. Group sequential statistical designs offer a mechanism to consider terminating a trial early and the results made public if the interim data become sufficiently compelling. Interim monitoring of safety and efficacy data is an integral part of modern clinical trials.

Authors
Sartor, O; Halabi, S
MLA Citation
Sartor, O, and Halabi, S. "Independent data monitoring committees: an update and overview." Urologic oncology 33.3 (March 2015): 143-148. (Review)
PMID
25631301
Source
epmc
Published In
Urologic Oncology: Seminars and Original Investigations
Volume
33
Issue
3
Publish Date
2015
Start Page
143
End Page
148
DOI
10.1016/j.urolonc.2014.12.013

Independent data monitoring committees: An update and overview

Authors
Sartor, O; Halabi, S
MLA Citation
Sartor, O, and Halabi, S. "Independent data monitoring committees: An update and overview." UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 33.3 (March 2015): 143-148.
Source
wos-lite
Published In
Urologic Oncology: Seminars and Original Investigations
Volume
33
Issue
3
Publish Date
2015
Start Page
143
End Page
148
DOI
10.1016/j.urolonc.2014.12.013

Sample Size Requirements and Study Duration for Testing Main Effects and Interactions in Completely Randomized Factorial Designs When Time to Event is the Outcome.

In this paper we develop the methodology for designing clinical trials with any factorial arrangement when the primary outcome is time to event. We provide a matrix formulation for calculating the sample size and study duration necessary to test any effect with a pre-specified type I error rate and power. Assuming that a time to event follows an exponential distribution, we describe the relationships between the effect size, the power, and the sample size. We present examples for illustration purposes. We provide a simulation study to verify the numerical calculations of the expected number of events and the duration of the trial. The change in the power produced by a reduced number of observations or by accruing no patients to certain factorial combinations is also described.

Authors
Moser, BK; Halabi, S
MLA Citation
Moser, BK, and Halabi, S. "Sample Size Requirements and Study Duration for Testing Main Effects and Interactions in Completely Randomized Factorial Designs When Time to Event is the Outcome." Communications in statistics: theory and methods 44.2 (January 2015): 275-285.
PMID
25530661
Source
epmc
Published In
Communication in Statistics Part A - Theory & Methods
Volume
44
Issue
2
Publish Date
2015
Start Page
275
End Page
285
DOI
10.1080/03610926.2012.705940

Reply to F. Valcamonico et al.

Authors
Smith, MR; Halabi, S; Small, EJ
MLA Citation
Smith, MR, Halabi, S, and Small, EJ. "Reply to F. Valcamonico et al." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32.32 (November 2014): 3685-.
PMID
25225438
Source
epmc
Published In
Journal of Clinical Oncology
Volume
32
Issue
32
Publish Date
2014
Start Page
3685
DOI
10.1200/jco.2014.57.3808

Adjusting for misclassification in a stratified biomarker clinical trial

Clinical trials utilizing predictive biomarkers have become a research focus in personalized medicine. We investigate the effects of biomarker misclassification on the design and analysis of stratified biomarker clinical trials. For a variety of inference problems including marker-treatment interaction in particular, we show that marker misclassification may have profound adverse effects on the coverage of confidence intervals, power of the tests, and required sample sizes. For each inferential problem, we propose methods to adjust for the classification errors. © 2014 John Wiley & Sons, Ltd.

Authors
Liu, C; Liu, A; Hu, J; Yuan, V; Halabi, S
MLA Citation
Liu, C, Liu, A, Hu, J, Yuan, V, and Halabi, S. "Adjusting for misclassification in a stratified biomarker clinical trial." Statistics in Medicine 33.18 (August 15, 2014): 3100-3113.
Source
scopus
Published In
Statistics in Medicine
Volume
33
Issue
18
Publish Date
2014
Start Page
3100
End Page
3113
DOI
10.1002/sim.6164

Adjusting for misclassification in a stratified biomarker clinical trial.

Clinical trials utilizing predictive biomarkers have become a research focus in personalized medicine. We investigate the effects of biomarker misclassification on the design and analysis of stratified biomarker clinical trials. For a variety of inference problems including marker-treatment interaction in particular, we show that marker misclassification may have profound adverse effects on the coverage of confidence intervals, power of the tests, and required sample sizes. For each inferential problem, we propose methods to adjust for the classification errors.

Authors
Liu, C; Liu, A; Hu, J; Yuan, V; Halabi, S
MLA Citation
Liu, C, Liu, A, Hu, J, Yuan, V, and Halabi, S. "Adjusting for misclassification in a stratified biomarker clinical trial." Statistics in medicine 33.18 (August 2014): 3100-3113.
PMID
24733510
Source
epmc
Published In
Statistics in Medicine
Volume
33
Issue
18
Publish Date
2014
Start Page
3100
End Page
3113
DOI
10.1002/sim.6164

ERRATA (vol 56, pg 5366, 2014)

Authors
Halabi, S
MLA Citation
Halabi, S. "ERRATA (vol 56, pg 5366, 2014)." JOURNAL OF CLINICAL ONCOLOGY 32.13 (May 1, 2014): 1387-1387.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
13
Publish Date
2014
Start Page
1387
End Page
1387
DOI
10.1200/JCO.2014.56.5366

Erratum

Authors
Halabi, S
MLA Citation
Halabi, S. "Erratum." JNCI Journal of the National Cancer Institute 106.4 (April 8, 2014): dju096-dju096.
Source
manual
Published In
Journal of the National Cancer Institute
Volume
106
Issue
4
Publish Date
2014
Start Page
dju096
End Page
dju096
DOI
10.1093/jnci/dju096

Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance).

Zoledronic acid decreases the risk for skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases but its role earlier in the natural history of the disease is unknown. This phase III study evaluated the efficacy and safety of earlier treatment with zoledronic acid in men with castration-sensitive metastatic prostate cancer.Men with castration-sensitive prostate cancer and bone metastases whose androgen-deprivation therapy was initiated within 6 months of study entry were randomly assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously every 4 weeks) or a placebo. After their disease progressed to castration-resistant status, all patients received open-label treatment with zoledronic acid. The primary end point was time to first SRE, defined as radiation to bone, clinical fracture, spinal cord compression, surgery to bone, or death as a result of prostate cancer. Target accrual was 680 patients. Primary analysis was planned after 470 SREs. The study was discontinued prematurely (645 patients; 299 SREs) after the corporate supporter withdrew study drug supply.Early zoledronic acid was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the zoledronic acid group (95% CI, 24.2 to 40.3) and 29.8 months in the placebo group (95% CI, 25.3 to 37.2; hazard ratio, 0.97; 95% CI, 0 to 1.17; one-sided stratified log-rank P = .39). Overall survival was similar between the groups (hazard ratio, 0.88; 95% CI, 0.70 to 1.12; P = .29). Rates of adverse events were similar between the groups.In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs.

Authors
Smith, MR; Halabi, S; Ryan, CJ; Hussain, A; Vogelzang, N; Stadler, W; Hauke, RJ; Monk, JP; Saylor, P; Bhoopalam, N; Saad, F; Sanford, B; Kelly, WK; Morris, M; Small, EJ
MLA Citation
Smith, MR, Halabi, S, Ryan, CJ, Hussain, A, Vogelzang, N, Stadler, W, Hauke, RJ, Monk, JP, Saylor, P, Bhoopalam, N, Saad, F, Sanford, B, Kelly, WK, Morris, M, and Small, EJ. "Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32.11 (April 2014): 1143-1150.
PMID
24590644
Source
epmc
Published In
Journal of Clinical Oncology
Volume
32
Issue
11
Publish Date
2014
Start Page
1143
End Page
1150
DOI
10.1200/jco.2013.51.6500

Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer.

Prognostic models for overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC) are dated and do not reflect significant advances in treatment options available for these patients. This work developed and validated an updated prognostic model to predict OS in patients receiving first-line chemotherapy.Data from a phase III trial of 1,050 patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401 [Alliance]). The data were randomly split into training and testing sets. A separate phase III trial served as an independent validation set. Adaptive least absolute shrinkage and selection operator selected eight factors prognostic for OS. A predictive score was computed from the regression coefficients and used to classify patients into low- and high-risk groups. The model was assessed for its predictive accuracy using the time-dependent area under the curve (tAUC).The model included Eastern Cooperative Oncology Group performance status, disease site, lactate dehydrogenase, opioid analgesic use, albumin, hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values in the high- and low-risk groups, respectively, in the testing set were 17 and 30 months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and 26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and 0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively.An updated prognostic model for OS in patients with mCRPC receiving first-line chemotherapy was developed and validated on an external set. This model can be used to predict OS, as well as to better select patients to participate in trials on the basis of their prognosis.

Authors
Halabi, S; Lin, C-Y; Kelly, WK; Fizazi, KS; Moul, JW; Kaplan, EB; Morris, MJ; Small, EJ
MLA Citation
Halabi, S, Lin, C-Y, Kelly, WK, Fizazi, KS, Moul, JW, Kaplan, EB, Morris, MJ, and Small, EJ. "Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32.7 (March 2014): 671-677.
PMID
24449231
Source
epmc
Published In
Journal of Clinical Oncology
Volume
32
Issue
7
Publish Date
2014
Start Page
671
End Page
677
DOI
10.1200/jco.2013.52.3696

Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma.

BACKGROUND: The current study was conducted to investigate the dependence between progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to explore whether PFS can be used as an intermediate endpoint of OS in this patient population. METHODS: A total of 1381 patients from 2 prospective phase 3 trials (Cancer and Leukemia Group B [CALGB] 90206 and AVOREN) of interferon-alpha with or without bevacizumab were analyzed. Both trials recruited previously untreated patients with clear cell mRCC with an Eastern Cooperative Oncology Group performance status of 0 to 2; adequate bone marrow, hepatic, cardiac, and renal function; and controlled blood pressure. The CALGB study served as the training data set, and the AVOREN study served as the testing data set. The dependence between PFS and OS was investigated using the Kendall tau for bivariate time-to-event endpoints. RESULTS: In the training data set, the median OS times among patients who experienced progressive disease at 3 months or 6 months were 6 months and 8 months, respectively, compared with 25 months and 30 months, respectively, (P < .001) in patients who did not develop disease progress. The adjusted hazard ratios (HR) were 2.6 (P < .0001) and 2.8 (P < .0001), respectively, for patients who did and did not progress at 3 months or 6 months. The dependence between PFS and OS was 0.53. These associations were confirmed in the testing data set. CONCLUSIONS: In patients with mRCC who were treated with interferon-alpha with or without bevacizumab, the PFS at 3 months and 6 months was found to be predictive of OS. A high dependence between PFS and OS was observed, suggesting that PFS may be used as a surrogate endpoint for OS. Although this is a novel observation for RCC, these findings require validation in patients with mRCC who are treated with other targeted agents.

Authors
Halabi, S; Rini, B; Escudier, B; Stadler, WM; Small, EJ
MLA Citation
Halabi, S, Rini, B, Escudier, B, Stadler, WM, and Small, EJ. "Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma." Cancer 120.1 (January 1, 2014): 52-60.
PMID
24347384
Source
pubmed
Published In
Cancer
Volume
120
Issue
1
Publish Date
2014
Start Page
52
End Page
60
DOI
10.1002/cncr.28221

A phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer

Background Phosphatase and tensin homologue (PTEN) loss is common in advanced prostate cancer, leading to constitutive activation of the PI3 kinase pathway. Temsirolimus blocks mammalian target of rapamycin (mTOR)/target of rapamycin complex 1 (TORC1), a key signaling node in this pathway; its activity in men with advanced castration-resistant metastatic prostate cancer (mCRPC) is unknown. Methods We conducted a single-arm trial of weekly intravenous temsirolimus administration in men with chemorefractory mCRPC who had ≥ 5 circulating tumor cells (CTCs) at baseline. The primary end point was the change in CTCs at 8 weeks; secondary end points were composite progression-free survival (PFS) (excluding prostate-specific antigen [PSA]), PSA and radiographic response rates, safety, and survival. At PSA/CTC progression, an anti-androgen could be added while continuing temsirolimus. Results Eleven patients were accrued out of a planned 20; the trial was stopped prematurely because of lack of efficacy/feasibility. Median age was 61 years, with 55% African-Americans and 36% Caucasian patients. Median baseline PSA level was 390 ng/dL, median baseline number of CTCs was 14 cells; 50% of patients had pain, and 63% had undergone ≥ 2 previous chemotherapy regimens. Median CTC decline was 48% and 3 patients experienced decline in CTCs to < 5. However, 73% of men had a persistently unfavorable number of CTCs (≥ 5) and only 1 patient had a ≥ 30% PSA decline. Median PFS was 1.9 months (95% confidence interval [CI], 0.9-3.1) and median overall survival (OS) was 8.8 months (95% CI, 3.1-15.6). Toxicities included grade 4 hypophosphatemia and central nervous system (CNS) hemorrhage, and frequent grade 3 fatigue, anemia, stomatitis, hypokalemia, weakness, and hyperglycemia. Conclusion Temsirolimus lacked sufficient clinical activity in men with mCRPC, despite transient CTC improvements in some men. Future studies should focus on combination approaches or novel PI3K pathway inhibitors. © 2013 Elsevier Inc. All rights reserved.

Authors
Armstrong, AJ; Shen, T; Halabi, S; Kemeny, G; Bitting, RL; Kartcheske, P; Embree, E; Morris, K; Winters, C; Jaffe, T; Fleming, M; George, DJ
MLA Citation
Armstrong, AJ, Shen, T, Halabi, S, Kemeny, G, Bitting, RL, Kartcheske, P, Embree, E, Morris, K, Winters, C, Jaffe, T, Fleming, M, and George, DJ. "A phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer." Clinical Genitourinary Cancer 11.4 (December 1, 2013): 397-406.
Source
scopus
Published In
Clinical genitourinary cancer
Volume
11
Issue
4
Publish Date
2013
Start Page
397
End Page
406
DOI
10.1016/j.clgc.2013.05.007

A phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer.

BACKGROUND: Phosphatase and tensin homologue (PTEN) loss is common in advanced prostate cancer, leading to constitutive activation of the PI3 kinase pathway. Temsirolimus blocks mammalian target of rapamycin (mTOR)/target of rapamycin complex 1 (TORC1), a key signaling node in this pathway; its activity in men with advanced castration-resistant metastatic prostate cancer (mCRPC) is unknown. METHODS: We conducted a single-arm trial of weekly intravenous temsirolimus administration in men with chemorefractory mCRPC who had ≥ 5 circulating tumor cells (CTCs) at baseline. The primary end point was the change in CTCs at 8 weeks; secondary end points were composite progression-free survival (PFS) (excluding prostate-specific antigen [PSA]), PSA and radiographic response rates, safety, and survival. At PSA/CTC progression, an anti-androgen could be added while continuing temsirolimus. RESULTS: Eleven patients were accrued out of a planned 20; the trial was stopped prematurely because of lack of efficacy/feasibility. Median age was 61 years, with 55% African-Americans and 36% Caucasian patients. Median baseline PSA level was 390 ng/dL, median baseline number of CTCs was 14 cells; 50% of patients had pain, and 63% had undergone ≥ 2 previous chemotherapy regimens. Median CTC decline was 48% and 3 patients experienced decline in CTCs to < 5. However, 73% of men had a persistently unfavorable number of CTCs (≥ 5) and only 1 patient had a ≥ 30% PSA decline. Median PFS was 1.9 months (95% confidence interval [CI], 0.9-3.1) and median overall survival (OS) was 8.8 months (95% CI, 3.1-15.6). Toxicities included grade 4 hypophosphatemia and central nervous system (CNS) hemorrhage, and frequent grade 3 fatigue, anemia, stomatitis, hypokalemia, weakness, and hyperglycemia. CONCLUSION: Temsirolimus lacked sufficient clinical activity in men with mCRPC, despite transient CTC improvements in some men. Future studies should focus on combination approaches or novel PI3K pathway inhibitors.

Authors
Armstrong, AJ; Shen, T; Halabi, S; Kemeny, G; Bitting, RL; Kartcheske, P; Embree, E; Morris, K; Winters, C; Jaffe, T; Fleming, M; George, DJ
MLA Citation
Armstrong, AJ, Shen, T, Halabi, S, Kemeny, G, Bitting, RL, Kartcheske, P, Embree, E, Morris, K, Winters, C, Jaffe, T, Fleming, M, and George, DJ. "A phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer." Clin Genitourin Cancer 11.4 (December 2013): 397-406.
PMID
23830964
Source
pubmed
Published In
Clinical genitourinary cancer
Volume
11
Issue
4
Publish Date
2013
Start Page
397
End Page
406
DOI
10.1016/j.clgc.2013.05.007

On model specification and selection of the Cox proportional hazards model.

Prognosis plays a pivotal role in patient management and trial design. A useful prognostic model should correctly identify important risk factors and estimate their effects. In this article, we discuss several challenges in selecting prognostic factors and estimating their effects using the Cox proportional hazards model. Although a flexible semiparametric form, the Cox's model is not entirely exempt from model misspecification. To minimize possible misspecification, instead of imposing traditional linear assumption, flexible modeling techniques have been proposed to accommodate the nonlinear effect. We first review several existing nonparametric estimation and selection procedures and then present a numerical study to compare the performance between parametric and nonparametric procedures. We demonstrate the impact of model misspecification on variable selection and model prediction using a simulation study and an example from a phase III trial in prostate cancer.

Authors
Lin, C-Y; Halabi, S
MLA Citation
Lin, C-Y, and Halabi, S. "On model specification and selection of the Cox proportional hazards model." Stat Med 32.26 (November 20, 2013): 4609-4623.
PMID
23784939
Source
pubmed
Published In
Statistics in Medicine
Volume
32
Issue
26
Publish Date
2013
Start Page
4609
End Page
4623
DOI
10.1002/sim.5876

Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy.

BACKGROUND: Several prognostic models for overall survival (OS) have been developed and validated in men with metastatic castration-resistant prostate cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and validate a prognostic model to predict OS in men who had progressed after first-line chemotherapy and were selected to receive second-line chemotherapy. METHODS: Data from a phase III trial in men with mCRPC who had developed progressive disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was randomly split into training (n = 507) and testing (n = 248) sets. Another dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was used for external validation. Adaptive least absolute shrinkage and selection operator selected nine prognostic factors of OS. A prognostic score was computed from the regression coefficients. The model was assessed on the testing and validation sets for its predictive accuracy using the time-dependent area under the curve (tAUC). RESULTS: The nine prognostic variables in the final model were Eastern Cooperative Oncology Group performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of hormonal use, hemoglobin, prostate specific antigen, and alkaline phosphatase. The tAUCs for this model were 0.73 (95% confidence interval [CI] = 0.72 to 0.74) and 0.70 (95% CI = 0.68 to 0.72) for the testing and validation sets, respectively. CONCLUSIONS: A prognostic model of OS in the postdocetaxel, second-line chemotherapy, mCRPC setting was developed and externally validated. This model incorporates novel prognostic factors and can be used to provide predicted probabilities for individual patients and to select patients to participate in clinical trials on the basis of their prognosis. Prospective validation is needed.

Authors
Halabi, S; Lin, C-Y; Small, EJ; Armstrong, AJ; Kaplan, EB; Petrylak, D; Sternberg, CN; Shen, L; Oudard, S; de Bono, J; Sartor, O
MLA Citation
Halabi, S, Lin, C-Y, Small, EJ, Armstrong, AJ, Kaplan, EB, Petrylak, D, Sternberg, CN, Shen, L, Oudard, S, de Bono, J, and Sartor, O. "Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy." J Natl Cancer Inst 105.22 (November 20, 2013): 1729-1737.
PMID
24136890
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
105
Issue
22
Publish Date
2013
Start Page
1729
End Page
1737
DOI
10.1093/jnci/djt280

Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy.

PURPOSE: Prostate-specific antigen (PSA) kinetics, and more specifically a ≥ 30% decline in PSA within 3 months after initiation of first-line chemotherapy with docetaxel, are associated with improvement in overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). The objective of this analysis was to evaluate post-treatment PSA kinetics as surrogates for OS in patients receiving second-line chemotherapy. PATIENTS AND METHODS: Data from a phase III trial of patients with mCRPC randomly assigned to cabazitaxel plus prednisone (C + P) or mitoxantrone plus prednisone were used. PSA decline (≥ 30% and ≥ 50%), velocity, and rise within the first 3 months of treatment were evaluated as surrogates for OS. The Prentice criteria, proportion of treatment explained (PTE), and meta-analytic approaches were used as measures of surrogacy. RESULTS: The observed hazard ratio (HR) for death for patients treated with C + P was 0.66 (95% CI, 0.55 to 0.79; P < .001). Furthermore, a ≥ 30% decline in PSA was a statistically significant predictor of OS (HR for death, 0.52; 95% CI, 0.43 to 0.64; P < .001). Adjusting for treatment effect, the HR for a ≥ 30% PSA decline was 0.50 (95% CI, 0.40 to 0.62; P < .001), but treatment remained statistically significant, thus failing the third Prentice criterion. The PTE for a ≥ 30% decline in PSA was 0.34 (95% CI, 0.11 to 0.56), indicating a lack of surrogacy for OS. The values of R(2) were < 1, suggesting that PSA decline was not surrogate for OS. CONCLUSION: Surrogacy for any PSA-based end point could not be demonstrated in this analysis. Thus, the benefits of cabazitaxel in mediating a survival benefit are not fully captured by early PSA changes.

Authors
Halabi, S; Armstrong, AJ; Sartor, O; de Bono, J; Kaplan, E; Lin, C-Y; Solomon, NC; Small, EJ
MLA Citation
Halabi, S, Armstrong, AJ, Sartor, O, de Bono, J, Kaplan, E, Lin, C-Y, Solomon, NC, and Small, EJ. "Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy." J Clin Oncol 31.31 (November 1, 2013): 3944-3950.
PMID
24101043
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
31
Issue
31
Publish Date
2013
Start Page
3944
End Page
3950
DOI
10.1200/JCO.2013.50.3201

The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance).

BACKGROUND: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODS: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTS: Baseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366). CONCLUSIONS: As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC.

Authors
Aggarwal, R; Halabi, S; Kelly, WK; George, D; Mahoney, JF; Millard, F; Stadler, WM; Morris, MJ; Kantoff, P; Monk, JP; Carducci, M; Small, EJ; Alliance for Clinical Trials in Oncology,
MLA Citation
Aggarwal, R, Halabi, S, Kelly, WK, George, D, Mahoney, JF, Millard, F, Stadler, WM, Morris, MJ, Kantoff, P, Monk, JP, Carducci, M, Small, EJ, and Alliance for Clinical Trials in Oncology, . "The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance)." Cancer 119.20 (October 15, 2013): 3636-3643.
PMID
23913744
Source
pubmed
Published In
Cancer
Volume
119
Issue
20
Publish Date
2013
Start Page
3636
End Page
3643
DOI
10.1002/cncr.28285

Prognostic Model for Predicting Survival of Patients With Metastatic Urothelial Cancer Treated With Cisplatin-Based Chemotherapy

Authors
Apolo, AB; Ostrovnaya, I; Halabi, S; Iasonos, A; Philips, GK; Rosenberg, JE; Riches, J; Small, EJ; Milowsky, MI; Bajorin, DF
MLA Citation
Apolo, AB, Ostrovnaya, I, Halabi, S, Iasonos, A, Philips, GK, Rosenberg, JE, Riches, J, Small, EJ, Milowsky, MI, and Bajorin, DF. "Prognostic Model for Predicting Survival of Patients With Metastatic Urothelial Cancer Treated With Cisplatin-Based Chemotherapy." JNCI Journal of the National Cancer Institute 105.7 (April 3, 2013): 499-503.
PMID
23411591
Source
crossref
Published In
Journal of the National Cancer Institute
Volume
105
Issue
7
Publish Date
2013
Start Page
499
End Page
503
DOI
10.1093/jnci/djt015

Reply to M A Khattak et al.

Authors
Armstrong, AJ; George, DJ; Halabi, S
MLA Citation
Armstrong, AJ, George, DJ, and Halabi, S. "Reply to M A Khattak et al." J Clin Oncol 31.7 (March 1, 2013): 972-973. (Letter)
PMID
23565533
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
31
Issue
7
Publish Date
2013
Start Page
972
End Page
973
DOI
10.1200/JCO.2012.47.7224

Prognostic and Predictive Markers in Metastatic Renal Cell Carcinoma Reply

Authors
Armstrong, AJ; George, DJ; Halabi, S
MLA Citation
Armstrong, AJ, George, DJ, and Halabi, S. "Prognostic and Predictive Markers in Metastatic Renal Cell Carcinoma Reply." JOURNAL OF CLINICAL ONCOLOGY 31.7 (March 1, 2013): 972-973.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
7
Publish Date
2013
Start Page
972
End Page
973
DOI
10.1200/JCO.2012.47.7224

The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: Results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance)

BACKGROUND Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODS In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTS Baseline characteristics between patients who did (N = 277) and did not (N = 728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P =.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P =.342), the proportion achieving a decline ≥50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P =.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P =.366). CONCLUSIONS As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC. Cancer 2013;119:3636-3643. © 2013 American Cancer Society.

Authors
Aggarwal, R; Halabi, S; Kelly, WK; George, D; Mahoney, JF; Millard, F; Stadler, WM; Morris, MJ; Kantoff, P; Monk, JP; Carducci, M; Small, EJ
MLA Citation
Aggarwal, R, Halabi, S, Kelly, WK, George, D, Mahoney, JF, Millard, F, Stadler, WM, Morris, MJ, Kantoff, P, Monk, JP, Carducci, M, and Small, EJ. "The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: Results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance)." Cancer 119.20 (2013): 3636-3643.
Source
scival
Published In
Cancer
Volume
119
Issue
20
Publish Date
2013
Start Page
3636
End Page
3643
DOI
10.1002/cncr.28285

On model specification and selection of the Cox proportional hazards model

Prognosis plays a pivotal role in patient management and trial design. A useful prognostic model should correctly identify important risk factors and estimate their effects. In this article, we discuss several challenges in selecting prognostic factors and estimating their effects using the Cox proportional hazards model. Although a flexible semiparametric form, the Cox's model is not entirely exempt from model misspecification. To minimize possible misspecification, instead of imposing traditional linear assumption, flexible modeling techniques have been proposed to accommodate the nonlinear effect. We first review several existing nonparametric estimation and selection procedures and then present a numerical study to compare the performance between parametric and nonparametric procedures. We demonstrate the impact of model misspecification on variable selection and model prediction using a simulation study and an example from a phase III trial in prostate cancer. © 2013 John Wiley & Sons, Ltd. © 2013 John Wiley & Sons, Ltd.

Authors
Lin, CY; Halabi, S
MLA Citation
Lin, CY, and Halabi, S. "On model specification and selection of the Cox proportional hazards model." Statistics in Medicine 32.26 (2013): 4609-4623.
Source
scival
Published In
Statistics in Medicine
Volume
32
Issue
26
Publish Date
2013
Start Page
4609
End Page
4623
DOI
10.1002/sim.5876

Residential mercury contamination in adobe brick homes in Huancavelica, Peru.

This is the first study of adobe brick contamination anywhere in the world. Huancavelica, Peru is the site of historic cinnabar refining and one of the most mercury (Hg) contaminated urban areas in the world. Over 80% of homes in Huancavelica are constructed with adobe bricks made from Hg contaminated soil. In this study we measured total Hg concentrations in adobe brick, dirt floor, surface dust, and air samples from the interior of 60 adobe brick houses located in four neighborhoods. Concentrations of total Hg in adobe bricks, dirt floors, and surface dust ranged from 8.00 to 1070 µg/g, 3.06 to 926 µg/g, and 0.02 to 9.69 µg/wipe, respectively, with statistically significant differences between the four neighborhoods. Concentrations of Hg in adobe brick and dirt floor samples in Huancavelica were orders of magnitude higher than in Ayacucho, a non-mining town in Peru. A strong correlation exists between total Hg concentrations in adobe bricks and dirt floors which confirms that adobe bricks were being made on-site and not purchased from an off-site source. A strong correlation between surface dust and adobe bricks and dirt floors indicates that walls and floors serve as indoor sources of Hg contamination. Elemental Hg vapor concentrations were below detection (<0.5 µg/m(3)) in most homes; however in homes with detectable levels, concentrations up to 5.1 µg/m(3) were observed. No statistically significant differences in Hg vapor measurements were observed between neighborhoods. This study demonstrates that building materials used widely in developing communities, such as adobe bricks, may be a substantial source of residential Hg exposure in silver or gold refining communities where Hg is produced or used for amalgamation in artisanal gold production.

Authors
Hagan, N; Robins, N; Hsu-Kim, H; Halabi, S; Espinoza Gonzales, RD; Richter, DD; Vandenberg, J
MLA Citation
Hagan, N, Robins, N, Hsu-Kim, H, Halabi, S, Espinoza Gonzales, RD, Richter, DD, and Vandenberg, J. "Residential mercury contamination in adobe brick homes in Huancavelica, Peru. (Published online)" PLoS One 8.9 (2013): e75179-.
PMID
24040399
Source
pubmed
Published In
PloS one
Volume
8
Issue
9
Publish Date
2013
Start Page
e75179
DOI
10.1371/journal.pone.0075179

Measurement of affective and activity pain interference using the Brief Pain Inventory (BPI): Cancer and Leukemia Group B 70903.

OBJECTIVE: The Brief Pain Inventory (BPI) was designed to yield separate scores for pain intensity and interference. It has been proposed that the pain interference factor can be further broken down into unique factors of affective (e.g., mood) and activity (e.g., work) interference. The purpose of this analysis was to confirm this affective/activity interference dichotomy. PATIENTS AND METHODS: A retrospective confirmatory factor analysis was completed for a sample of 184 individuals diagnosed with castrate-resistant prostate cancer (age 40-86, mean = 65.46, 77% White non-Hispanic) who had been administered the BPI as part of Cancer and Leukemia Group B trial 9480. A one-factor model was compared against two-factor and three-factor models that were developed based on the design of the instrument. RESULTS: Root mean squared error of approximation (0.075), comparative fit index (0.971), and change in chi-square, given the corresponding change in degrees of freedom (13.33, P < 0.05) values for the three-factor model (i.e., pain intensity, activity interference, and affective interference), were statistically superior in comparison with the one- and two-factor models. This three-factor structure was found to be invariant across age, mean prostate-specific antigen, and hemoglobin levels. CONCLUSIONS: These results confirm that the BPI can be used to quantify the degree to which pain separately interferes with affective and activity aspects of a patient's everyday life. These findings will provide clinical trialists, pharmaceutical sponsors, and regulators with confidence in the flexibility of the BPI as they consider the use of this instrument to assist with understanding the patient experience as it relates to treatment.

Authors
Atkinson, TM; Halabi, S; Bennett, AV; Rogak, L; Sit, L; Li, Y; Kaplan, E; Basch, E; Cancer and Leukemia Group B,
MLA Citation
Atkinson, TM, Halabi, S, Bennett, AV, Rogak, L, Sit, L, Li, Y, Kaplan, E, Basch, E, and Cancer and Leukemia Group B, . "Measurement of affective and activity pain interference using the Brief Pain Inventory (BPI): Cancer and Leukemia Group B 70903." Pain Med 13.11 (November 2012): 1417-1424.
PMID
23110676
Source
pubmed
Published In
Pain Medicine
Volume
13
Issue
11
Publish Date
2012
Start Page
1417
End Page
1424
DOI
10.1111/j.1526-4637.2012.01498.x

Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin.

PURPOSE: Lactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and regulated by the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR)-containing complex 1 (PI3K/Akt/TORC1) pathway as well as tumor hypoxia/necrosis. High serum LDH levels are associated with poor prognosis in patients with cancer, including renal cell carcinoma (RCC). We tested whether serum LDH is prognostic and has predictive value in patients with metastatic RCC receiving an mTOR inhibitor. PATIENTS AND METHODS: We evaluated pretreatment and post-treatment serum LDH in 404 poor-risk patients with RCC treated with the TORC1 inhibitor temsirolimus or interferon alfa in an international phase III randomized trial. The proportional hazards model was used to test for the prognostic and predictive association of LDH in predicting overall survival (OS). RESULTS: Mean baseline serum normalized LDH was 1.23 times the upper limit of normal (ULN; range, 0.05 to 28.5 × ULN). The multivariable hazard ratio for death was 2.81 (95% CI, 2.01 to 3.94; P < .001) for patients with LDH more than 1 × ULN versus patients with LDH ≤ 1 × ULN. The LDH-treatment interaction term was statistically significant for OS (P = .016). Among 140 patients with LDH above the ULN, OS was significantly improved with temsirolimus (6.9 v 4.2 months; P < .002). Among 264 patients with normal LDH, OS was not significantly improved with temsirolimus as compared with interferon therapy (11.7 v 10.4 months; P = .514). CONCLUSION: Serum LDH is a prognostic and a predictive biomarker for the survival benefit conferred by TORC1 inhibition in poor-risk RCC. Further investigation of the predictive role of LDH as a measure of benefit with PI3K/TORC1 pathway inhibition in other RCC risk groups and other tumor types is warranted.

Authors
Armstrong, AJ; George, DJ; Halabi, S
MLA Citation
Armstrong, AJ, George, DJ, and Halabi, S. "Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin." J Clin Oncol 30.27 (September 20, 2012): 3402-3407.
PMID
22891270
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
30
Issue
27
Publish Date
2012
Start Page
3402
End Page
3407
DOI
10.1200/JCO.2011.40.9631

Efficacy of peripheral androgen blockade in prostate cancer patients with biochemical failure after definitive local therapy: results of Cancer and Leukemia Group B (CALGB) 9782.

BACKGROUND: The treatment for prostate cancer patients with biochemical failure after local therapy remains controversial. Peripheral androgen blockade using a combination of a 5-alpha reductase inhibitor and an antiandrogen may allow control of the prostate-specific antigen (PSA). Because testosterone levels are not suppressed, this approach may be associated with less morbidity than conventional gonadal androgen suppression. METHODS: All patients had undergone previous definitive local therapy and had evidence of a rising PSA >1ng/mL, with no evidence of recurrent disease. Patients received both finasteride, 5 mg orally per day, and flutamide, 250 mg orally 3× a day. Patients were followed for a PSA response and quality of life assessment. RESULTS: Ninety-nine of 101 accrued patients were eligible. A ≥80% PSA decline was seen in 96 (96%) patients. The median time to PSA progression was 85 months. With a median follow-up of 10 years, the median survival time had not been reached, and the 5-year overall survival rate was 87%. Toxicity was mild, with 18 patients stopping for toxicity; 15 had diarrhea, 4 had gynecomastia, and 3 had transaminase elevation. Baseline Functional Assessment of Cancer Therapy Prostate Module and Treatment Outcome Index scores decreased by 5 points each at 6 months after enrollment. CONCLUSIONS: The use of the finasteride/flutamide combination is feasible, and results in PSA declines of ≥80% in 96% of patients with serologic progression after definitive local therapy. There were no unexpected toxicities, and the change in quality of life was mild. Further evaluation of this or a similar regimen in a controlled clinical trial is warranted.

Authors
Monk, JP; Halabi, S; Picus, J; Hussain, A; Philips, G; Kaplan, E; Ahles, T; Gu, L; Vogelzang, N; Kelly, WK; Small, EJ; Cancer and Leukemia Group B,
MLA Citation
Monk, JP, Halabi, S, Picus, J, Hussain, A, Philips, G, Kaplan, E, Ahles, T, Gu, L, Vogelzang, N, Kelly, WK, Small, EJ, and Cancer and Leukemia Group B, . "Efficacy of peripheral androgen blockade in prostate cancer patients with biochemical failure after definitive local therapy: results of Cancer and Leukemia Group B (CALGB) 9782." Cancer 118.17 (September 1, 2012): 4139-4147.
PMID
22180287
Source
pubmed
Published In
Cancer
Volume
118
Issue
17
Publish Date
2012
Start Page
4139
End Page
4147
DOI
10.1002/cncr.26732

Estimations of historical atmospheric mercury concentrations from mercury refining and present-day soil concentrations of total mercury in Huancavelica, Peru.

Detailed Spanish records of cinnabar mining and mercury production during the colonial period in Huancavelica, Peru were examined to estimate historical health risks to the community from exposure to elemental mercury (Hg) vapor resulting from cinnabar refining operations. Between 1564 and 1810, nearly 17,000 metric tons of Hg were released to the atmosphere in Huancavelica from Hg production. AERMOD was used with estimated emissions and source characteristics to approximate historic atmospheric concentrations of mercury vapor. Modeled 1-hour and long-term concentrations were compared with present-day inhalation reference values for elemental Hg. Estimated 1-hour maximum concentrations for the entire community exceeded present-day occupational inhalation reference values, while some areas closest to the smelters exceeded present-day emergency response guideline levels. Estimated long-term maximum concentrations for the entire community exceeded the EPA Reference Concentration (RfC) by a factor of 30 to 100, with areas closest to the smelters exceeding the RfC by a factor of 300 to 1000. Based on the estimated historical concentrations of Hg vapor in the community, the study also measured the extent of present-day contamination throughout the community through soil sampling and analysis. Total Hg in soils sampled from 20 locations ranged from 1.75 to 698 mg/kg and three adobe brick samples ranging from 47.4 to 284 mg/kg, consistent with other sites of mercury mining and use. The results of the soil sampling indicate that the present-day population of Huancavelica is exposed to levels of mercury from legacy contamination which is currently among the highest worldwide, consequently placing them at potential risk of adverse health outcomes.

Authors
Robins, NA; Hagan, N; Halabi, S; Hsu-Kim, H; Gonzales, RDE; Morris, M; Woodall, G; Richter, DD; Heine, P; Zhang, T; Bacon, A; Vandenberg, J
MLA Citation
Robins, NA, Hagan, N, Halabi, S, Hsu-Kim, H, Gonzales, RDE, Morris, M, Woodall, G, Richter, DD, Heine, P, Zhang, T, Bacon, A, and Vandenberg, J. "Estimations of historical atmospheric mercury concentrations from mercury refining and present-day soil concentrations of total mercury in Huancavelica, Peru." Sci Total Environ 426 (June 1, 2012): 146-154.
PMID
22542225
Source
pubmed
Published In
Science of the Total Environment
Volume
426
Publish Date
2012
Start Page
146
End Page
154
DOI
10.1016/j.scitotenv.2012.03.082

Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401.

PURPOSE: A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m(2) intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity. RESULTS: In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005). CONCLUSION: Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity.

Authors
Kelly, WK; Halabi, S; Carducci, M; George, D; Mahoney, JF; Stadler, WM; Morris, M; Kantoff, P; Monk, JP; Kaplan, E; Vogelzang, NJ; Small, EJ
MLA Citation
Kelly, WK, Halabi, S, Carducci, M, George, D, Mahoney, JF, Stadler, WM, Morris, M, Kantoff, P, Monk, JP, Kaplan, E, Vogelzang, NJ, and Small, EJ. "Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401." J Clin Oncol 30.13 (May 1, 2012): 1534-1540.
PMID
22454414
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
30
Issue
13
Publish Date
2012
Start Page
1534
End Page
1540
DOI
10.1200/JCO.2011.39.4767

Adjustment on the Type I Error Rate for a Clinical Trial Monitoring for both Intermediate and Primary Endpoints.

In many clinical trials, a single endpoint is used to answer the primary question and forms the basis for monitoring the experimental therapy. Many trials are lengthy in duration and investigators are interested in using an intermediate endpoint for an accelerated approval, but will rely on the primary endpoint (such as, overall survival) for the full approval of the drug by the Food and Drug Administration. We have designed a clinical trial where both intermediate (progression-free survival, (PFS)) and primary endpoints (overall survival, (OS)) are used for monitoring the trial so the overall type I error rate is preserved at the pre-specified alpha level of 0.05. A two-stage procedure is used. In the first stage, the Bonferroni correction was used where the global type I error rate was allocated to each of the endpoints. In the next stage, the O'Brien-Fleming approach was used to design the boundary for the interim and final analysis for each endpoint. Data were generated assuming several parametric copulas with exponential marginals. Different degrees of dependence, as measured by Kendall's τ, between OS and PFS were assumed: 0 (independence) 0.3, 0.5 and 0.70. This approach is applied to an example in a prostate cancer trial.

Authors
Halabi, S
MLA Citation
Halabi, S. "Adjustment on the Type I Error Rate for a Clinical Trial Monitoring for both Intermediate and Primary Endpoints." Journal of biometrics & biostatistics 7 (May 2012): 15-.
PMID
24466469
Source
epmc
Published In
Journal of Biometrics and Biostatistics
Volume
7
Publish Date
2012
Start Page
15

MEASUREMENT OF AFFECTIVE AND ACTIVITY PAIN INTERFERENCE USING THE BRIEF PAIN INVENTORY

Authors
Atkinson, TM; Small, EJ; Rogak, L; Sit, L; Barragan, N; Shaw, M; Pollick, L; Ryan, SJ; Heon, N; Bennett, AV; Kaplan, E; Halabi, S; Basch, E
MLA Citation
Atkinson, TM, Small, EJ, Rogak, L, Sit, L, Barragan, N, Shaw, M, Pollick, L, Ryan, SJ, Heon, N, Bennett, AV, Kaplan, E, Halabi, S, and Basch, E. "MEASUREMENT OF AFFECTIVE AND ACTIVITY PAIN INTERFERENCE USING THE BRIEF PAIN INVENTORY." ANNALS OF BEHAVIORAL MEDICINE 43 (April 2012): S222-S222.
Source
wos-lite
Published In
Annals of Behavioral Medicine
Volume
43
Publish Date
2012
Start Page
S222
End Page
S222

Biomarkers in the management and treatment of men with metastatic castration-resistant prostate cancer.

CONTEXT: We have recently witnessed a rapid increase in the number of effective systemic agents for men with metastatic castration-resistant prostate cancer (CRPC), including novel hormonal therapies (abiraterone acetate and MDV3100), immunotherapies (sipuleucel-T), chemotherapies (cabazitaxel), and bone microenvironment targeting agents (denosumab, radium 223). Given the increasing complexity of treatment decisions for this disease, major research and clinical priorities are (1) finding biomarkers that enable an understanding of the natural history and complex biology of this heterogeneous malignancy, (2) defining predictive biomarkers that identify men most likely to benefit from a given therapy, and (3) identifying biomarkers of early response or progression to optimize outcomes. OBJECTIVE: In this review, we discuss existing and potential biomarkers in CRPC and how they may currently inform prognosis, aid in treatment selection (predictive value), and relate to survival outcomes (surrogacy). EVIDENCE ACQUISITION: PubMed-based literature searches and abstracts through September 2011 provided the basis for this literature review as well as expert opinion. EVIDENCE SYNTHESIS: We address blood and urine-based biomarkers such as prostate-specific antigen, lactate dehydrogenase, total and bone alkaline phosphatase and other bone turnover markers, hemoglobin, and circulating tumor cells in the context of prognosis, prediction, and patient selection for therapy. Given the inherent problems associated with defining progression-free survival in CRPC, the importance of biomarker development and the needed steps are highlighted. We place the discussion of biomarkers within the context of the design/intent of a trial and mechanism of action of a given systemic therapy. We discuss novel biomarker development and the pathway for surrogate or predictive biomarkers to become credentialed as useful tests that inform therapeutic decisions. CONCLUSIONS: A greater understanding of biomarkers in CRPC permits a more personalized approach to care that maximizes benefit and minimizes harm and can inform clinical trials tailored to men most likely to derive benefit.

Authors
Armstrong, AJ; Eisenberger, MA; Halabi, S; Oudard, S; Nanus, DM; Petrylak, DP; Sartor, AO; Scher, HI
MLA Citation
Armstrong, AJ, Eisenberger, MA, Halabi, S, Oudard, S, Nanus, DM, Petrylak, DP, Sartor, AO, and Scher, HI. "Biomarkers in the management and treatment of men with metastatic castration-resistant prostate cancer." Eur Urol 61.3 (March 2012): 549-559. (Review)
PMID
22099611
Source
pubmed
Published In
European Urology
Volume
61
Issue
3
Publish Date
2012
Start Page
549
End Page
559
DOI
10.1016/j.eururo.2011.11.009

Design issues in randomized phase II/III trials.

Phase II trials are used to show sufficient preliminary activity of a new treatment (in single-arm designs or randomized screening designs) or to select among treatments with demonstrated activity (in randomized selection designs). The treatments prioritized in a phase II trial are then tested definitively against a control treatment in a randomized phase III trial. Randomized phase II/III trials use an adaptive trial design that combines these two types of trials in one, with potential gains in time and reduced numbers of patients required to be treated. Two key considerations in designing a phase II/III trial are whether to suspend accrual while the phase II data mature and the choice of phase II target treatment effect. We discuss these phase II/III design parameters, give examples of phase II/III trials, and provide recommendations concerning efficient phase II/III trial designs.

Authors
Korn, EL; Freidlin, B; Abrams, JS; Halabi, S
MLA Citation
Korn, EL, Freidlin, B, Abrams, JS, and Halabi, S. "Design issues in randomized phase II/III trials." J Clin Oncol 30.6 (February 20, 2012): 667-671.
PMID
22271475
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
30
Issue
6
Publish Date
2012
Start Page
667
End Page
671
DOI
10.1200/JCO.2011.38.5732

Evaluating the effect of tobacco on prostate cancer outcomes with VEGF-targeted therapy.

Authors
Harzstark, AL; Halabi, S; Kelly, WK; Morris, MJ; Febbo, PG; Small, EJ
MLA Citation
Harzstark, AL, Halabi, S, Kelly, WK, Morris, MJ, Febbo, PG, and Small, EJ. "Evaluating the effect of tobacco on prostate cancer outcomes with VEGF-targeted therapy." JOURNAL OF CLINICAL ONCOLOGY 30.5 (February 10, 2012).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
30
Issue
5
Publish Date
2012

Estimation and testing of the relative risk of disease in case-control studies with a set of k matched controls per case with known prevalence of disease.

The analysis of case-control studies with matched controls per case is well documented in the medical literature. Of primary interest is the estimation of the relative risk of disease. Matched case-control studies fall into two scenarios: the probability of exposure is constant within each of the case and control groups, or the probability of exposure varies within each group. Numerous estimation procedures have been developed for both scenarios. Often these procedures are developed under the rare disease assumption, where the relative risk of disease is approximated by the odds ratio. In this paper, without making the rare disease assumption, we develop consistent estimators of the relative risk of disease for both scenarios. Exact derivations of the relative risk of disease are provided. Estimators, confidence intervals, and test statistics for the relative risk of disease are developed. We then make the following observations based on extensive simulations. First, our estimators are as close or closer to the relative risk of disease than other estimators. Second, our estimators produce mean square errors for the relative risk of disease that are as good as or better than these other estimators. Third, our confidence intervals provide accurate coverage probabilities. Therefore, these new estimators, confidence intervals, and test statistics can be used to either estimate or test the relative risk of disease in matched case-control studies.

Authors
Moser, BK; Halabi, S
MLA Citation
Moser, BK, and Halabi, S. "Estimation and testing of the relative risk of disease in case-control studies with a set of k matched controls per case with known prevalence of disease." Stat Med 31.1 (January 13, 2012): 29-44.
PMID
22162127
Source
pubmed
Published In
Statistics in Medicine
Volume
31
Issue
1
Publish Date
2012
Start Page
29
End Page
44
DOI
10.1002/sim.4414

Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809.

BACKGROUND: Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented. METHODS: Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises>1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival. RESULTS: Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%. CONCLUSIONS: In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer.

Authors
Hurwitz, MD; Halabi, S; Archer, L; McGinnis, LS; Kuettel, MR; DiBiase, SJ; Small, EJ
MLA Citation
Hurwitz, MD, Halabi, S, Archer, L, McGinnis, LS, Kuettel, MR, DiBiase, SJ, and Small, EJ. "Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809." Cancer 117.24 (December 15, 2011): 5579-5588.
PMID
22535500
Source
pubmed
Published In
Cancer
Volume
117
Issue
24
Publish Date
2011
Start Page
5579
End Page
5588
DOI
10.1002/cncr.26203

A min-max combination of biomarkers to improve diagnostic accuracy.

Diagnostic accuracy can be improved considerably by combining multiple biomarkers. Although the likelihood ratio provides optimal solution to combination of biomarkers, the method is sensitive to distributional assumptions which are often difficult to justify. Alternatively simple linear combinations can be considered whose empirical solution may encounter intensive computation when the number of biomarkers is relatively large. Moreover, the optimal linear combinations derived under multivariate normality may suffer substantial loss of efficiency if the distributions are apart from normality. In this paper, we propose a new approach that linearly combines the minimum and maximum values of the biomarkers. Such combination only involves searching for a single combination coefficient that maximizes the area under the receiver operating characteristic (ROC) curves and is thus computation-effective. Simulation results show that the min-max combination may yield larger partial or full area under the ROC curves and is more robust against distributional assumptions. The methods are illustrated using the growth-related hormones data from the Growth and Maturation in Children with Autism or Autistic Spectrum Disorder Study (Autism/ASD Study).

Authors
Liu, C; Liu, A; Halabi, S
MLA Citation
Liu, C, Liu, A, and Halabi, S. "A min-max combination of biomarkers to improve diagnostic accuracy." Stat Med 30.16 (July 20, 2011): 2005-2014.
PMID
21472763
Source
pubmed
Published In
Statistics in Medicine
Volume
30
Issue
16
Publish Date
2011
Start Page
2005
End Page
2014
DOI
10.1002/sim.4238

Investigator-initiated pilot study of sunitinib malate in patients with newly diagnosed prostate cancer prior to prostatectomy: A trial of the DoD/PCF Prostate Cancer Clinical Trials Consortium

Authors
George, DJ; Halabi, S; Zurita, AJ; Creel, P; Mundy, K; Turnbull, JD; Wood, SEY; Armstrong, AJ; Varley, RJ; Madden, J; Moul, JW
MLA Citation
George, DJ, Halabi, S, Zurita, AJ, Creel, P, Mundy, K, Turnbull, JD, Wood, SEY, Armstrong, AJ, Varley, RJ, Madden, J, and Moul, JW. "Investigator-initiated pilot study of sunitinib malate in patients with newly diagnosed prostate cancer prior to prostatectomy: A trial of the DoD/PCF Prostate Cancer Clinical Trials Consortium." May 20, 2011.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
15
Publish Date
2011

Comorbidities predict overall survival (OS) in men with metastatic castrate-resistant prostate cancer (CRPC)

Authors
Halabi, S; Kelly, WK; George, DJ; Morris, MJ; Kaplan, EB; Small, EJ
MLA Citation
Halabi, S, Kelly, WK, George, DJ, Morris, MJ, Kaplan, EB, and Small, EJ. "Comorbidities predict overall survival (OS) in men with metastatic castrate-resistant prostate cancer (CRPC)." JOURNAL OF CLINICAL ONCOLOGY 29.7 (March 1, 2011).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
29
Issue
7
Publish Date
2011

Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: final results from CALGB trial 79809.

BACKGROUND: Chemotherapy-induced ovarian failure (CIOF) is a frequent side-effect of adjuvant chemotherapy that results in rapid bone loss. We hypothesised that zoledronic acid (ZA), a third-generation amino bisphosphonate, would prevent bone loss in premenopausal women who developed CIOF. METHODS: Women (439) were randomised to intravenous (i.v.) ZA 4 mg every 3 months for 2 years starting within 1-3 months after randomization (arm A) or 1 year after randomization (arm B, controls). CIOF was prospectively defined as ≥ 3 months of amenorrhoea, follicle-stimulating hormone (FSH) ≥ 30 MIU/ml and non-pregnant at 1 year. The primary end-point was the percentage change in bone mineral density (BMD) in the lumbar spine (LS) from baseline to 12 months in the ZA and in control groups in women who developed CIOF; the secondary end-point was BMD in LS at 3 years in all randomised women. FINDINGS: One hundred and fifty (56%) met the definition of CIOF at 1 year. Overall, grade 3 toxicities of ZA were fatigue (1%) arthralgias (21%) and pain (84%). The median percent change (interquartile range, IQR) at 1 year was +1.2% (-0.5% to +2.8%) and -6.7% (-9.7% to -2.9%) p<0.001 and at 3 years was +1.0% (-1.6% to +5.2%) and -0.5% (-3.7% to +3.2%) p=0.019 in arms A and B, respectively. INTERPRETATION: ZA every 3 months is well tolerated and prevents rapid bone loss in premenopausal women that develop CIOF. Giving ZA with rather than 1 year after the start of adjuvant chemotherapy is the preferred sequence to prevent bone loss.

Authors
Shapiro, CL; Halabi, S; Hars, V; Archer, L; Weckstein, D; Kirshner, J; Sikov, W; Winer, E; Burstein, HJ; Hudis, C; Isaacs, C; Schilsky, R; Paskett, E
MLA Citation
Shapiro, CL, Halabi, S, Hars, V, Archer, L, Weckstein, D, Kirshner, J, Sikov, W, Winer, E, Burstein, HJ, Hudis, C, Isaacs, C, Schilsky, R, and Paskett, E. "Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: final results from CALGB trial 79809." Eur J Cancer 47.5 (March 2011): 683-689.
PMID
21324674
Source
pubmed
Published In
European Journal of Cancer
Volume
47
Issue
5
Publish Date
2011
Start Page
683
End Page
689
DOI
10.1016/j.ejca.2010.11.024

A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer: results from Cancer and Leukemia Group B Study 90006.

BACKGROUND: The use of docetaxel prolongs survival for patients with castrate-resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC. METHODS: This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m² docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate-specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression-free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival. RESULTS: Seventy-nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty-three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty-four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity. CONCLUSIONS: The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing.

Authors
Picus, J; Halabi, S; Kelly, WK; Vogelzang, NJ; Whang, YE; Kaplan, EB; Stadler, WM; Small, EJ; Cancer and Leukemia Group B,
MLA Citation
Picus, J, Halabi, S, Kelly, WK, Vogelzang, NJ, Whang, YE, Kaplan, EB, Stadler, WM, Small, EJ, and Cancer and Leukemia Group B, . "A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer: results from Cancer and Leukemia Group B Study 90006." Cancer 117.3 (February 1, 2011): 526-533.
PMID
20862750
Source
pubmed
Published In
Cancer
Volume
117
Issue
3
Publish Date
2011
Start Page
526
End Page
533
DOI
10.1002/cncr.25421

Estimating historical atmospheric mercury concentrations from silver mining and their legacies in present-day surface soil in Potosí, Bolivia

Detailed Spanish records of mercury use and silver production during the colonial period in Potosí, Bolivia were evaluated to estimate atmospheric emissions of mercury from silver smelting. Mercury was used in the silver production process in Potosí and nearly 32,000 metric tons of mercury were released to the environment. AERMOD was used in combination with the estimated emissions to approximate historical air concentrations of mercury from colonial mining operations during 1715, a year of relatively low silver production. Source characteristics were selected from archival documents, colonial maps and images of silver smelters in Potosí and a base case of input parameters was selected. Input parameters were varied to understand the sensitivity of the model to each parameter. Modeled maximum 1-h concentrations were most sensitive to stack height and diameter, whereas an index of community exposure was relatively insensitive to uncertainty in input parameters. Modeled 1-h and long-term concentrations were compared to inhalation reference values for elemental mercury vapor. Estimated 1-h maximum concentrations within 500 m of the silver smelters consistently exceeded present-day occupational inhalation reference values. Additionally, the entire community was estimated to have been exposed to levels of mercury vapor that exceed present-day acute inhalation reference values for the general public. Estimated long-term maximum concentrations of mercury were predicted to substantially exceed the EPA Reference Concentration for areas within 600 m of the silver smelters. A concentration gradient predicted by AERMOD was used to select soil sampling locations along transects in Potosí. Total mercury in soils ranged from 0.105 to 155 mg kg-1, among the highest levels reported for surface soils in the scientific literature. The correlation between estimated air concentrations and measured soil concentrations will guide future research to determine the extent to which the current community of Potosí and vicinity is at risk of adverse health effects from historical mercury contamination. © 2010 Elsevier Ltd.

Authors
Hagan, N; Robins, N; Hsu-Kim, H; Halabi, S; Morris, M; Woodall, G; Zhang, T; Bacon, A; Richter, DDB; Vandenberg, J
MLA Citation
Hagan, N, Robins, N, Hsu-Kim, H, Halabi, S, Morris, M, Woodall, G, Zhang, T, Bacon, A, Richter, DDB, and Vandenberg, J. "Estimating historical atmospheric mercury concentrations from silver mining and their legacies in present-day surface soil in Potosí, Bolivia." Atmospheric Environment 45.40 (January 1, 2011): 7619-7626.
Source
scopus
Published In
Atmospheric Environment
Volume
45
Issue
40
Publish Date
2011
Start Page
7619
End Page
7626
DOI
10.1016/j.atmosenv.2010.10.009

A min-max combination of biomarkers to improve diagnostic accuracy

Authors
Liu, C; Liu, A; Halabi, S
MLA Citation
Liu, C, Liu, A, and Halabi, S. "A min-max combination of biomarkers to improve diagnostic accuracy." Statistics in Medicine 30.27 (2011): 3266--.
Source
scival
Published In
Statistics in Medicine
Volume
30
Issue
27
Publish Date
2011
Start Page
3266-
DOI
10.1002/sim.4317

Bevacizumab and everolimus in renal cancer: a rational way forward.

Authors
Stadler, WM; Phillips, G; George, DJ; Halabi, S; Small, E
MLA Citation
Stadler, WM, Phillips, G, George, DJ, Halabi, S, and Small, E. "Bevacizumab and everolimus in renal cancer: a rational way forward." J Clin Oncol 28.33 (November 20, 2010): e692-e693. (Letter)
PMID
20940194
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
33
Publish Date
2010
Start Page
e692
End Page
e693
DOI
10.1200/JCO.2010.30.7934

Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer.

BACKGROUND: Tamoxifen use has been associated with increased risk of thromboembolic events (TEs) in women with breast cancer and women at high risk for the disease. Factor V Leiden (FVL) is the most common inherited clotting factor mutation and also confers increased thrombosis risk. We investigated whether FVL was associated with TE risk in women with early-stage breast cancer who took adjuvant tamoxifen. METHODS: A case-control study was conducted among 34 Cancer and Leukemia Group B (CALGB) institutions. We matched each of 124 women who had experienced a documented TE while taking adjuvant tamoxifen for breast cancer (but who were not necessarily on a CALGB treatment trial) to two control subjects (women who took adjuvant tamoxifen but did not experience TE) by age at diagnosis (+/-5 years). DNA from blood was analyzed for FVL mutations. Conditional logistic regression was used to estimate odds ratios (ORs) and to evaluate other potential factors associated with TE and tamoxifen use. All P values are based on two-sided tests. RESULTS: FVL mutations were identified in 23 (18.5%) case and 12 (4.8%) control subjects (OR = 4.66, 95% confidence interval = 2.14 to 10.14, P < .001). In the multivariable model, FVL mutation was associated with TE (OR = 4.73, 95% confidence interval = 2.10 to 10.68, P < .001). Other statistically significant factors associated with TE risk were personal history of TE and smoking. CONCLUSIONS: Among women taking adjuvant tamoxifen for early-stage breast cancer, those who had a TE were nearly five times more likely to carry a FVL mutation than those who did not have a TE. Postmenopausal women should be evaluated for the FVL mutation before prescription of adjuvant tamoxifen if a positive test would alter therapeutic decision making.

Authors
Garber, JE; Halabi, S; Tolaney, SM; Kaplan, E; Archer, L; Atkins, JN; Edge, S; Shapiro, CL; Dressler, L; Paskett, ED; Kimmick, G; Orcutt, J; Scalzo, A; Winer, E; Levine, E; Shahab, N; Berliner, N; Cancer and Leukemia Group B,
MLA Citation
Garber, JE, Halabi, S, Tolaney, SM, Kaplan, E, Archer, L, Atkins, JN, Edge, S, Shapiro, CL, Dressler, L, Paskett, ED, Kimmick, G, Orcutt, J, Scalzo, A, Winer, E, Levine, E, Shahab, N, Berliner, N, and Cancer and Leukemia Group B, . "Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer." J Natl Cancer Inst 102.13 (July 7, 2010): 942-949.
PMID
20554945
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
102
Issue
13
Publish Date
2010
Start Page
942
End Page
949
DOI
10.1093/jnci/djq211

A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALGB 90401

Authors
Kelly, WK; Halabi, S; Carducci, MA; George, DJ; Mahoney, JF; Stadler, WM; Morris, MJ; Kantoff, PW; III, MJP; Small, EJ; Grp, CL
MLA Citation
Kelly, WK, Halabi, S, Carducci, MA, George, DJ, Mahoney, JF, Stadler, WM, Morris, MJ, Kantoff, PW, III, MJP, Small, EJ, and Grp, CL. "A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALGB 90401." JOURNAL OF CLINICAL ONCOLOGY 28.18 (June 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
18
Publish Date
2010

A pharmacodynamic study of rapamycin in men with intermediate- to high-risk localized prostate cancer.

PURPOSE: Given discrepancies between preclinical and clinical observations of mammalian target of rapamycin (mTOR) inhibition in prostate cancer, we sought to determine the pharmacodynamic effects of the mTOR/TORC1 inhibitor rapamycin in men with intermediate- to high-risk prostate cancer undergoing radical prostatectomy. EXPERIMENTAL DESIGN: Rapamycin was given at 3 or 6 mg orally for 14 days before radical prostatectomy in men with multifocal Gleason sum > or =7 prostate cancer; 10 untreated control subjects were included. The primary outcome was inhibition of phosphorylation of ribosomal S6 in posttreatment radical prostatectomy versus pretreatment biopsy tumor tissue, evaluated using a Simon two-stage design for pharmacodynamic efficacy. RESULTS: Thirty-two subjects were accrued: 20 at 3 mg, 2 at 6 mg, and 10 controls. No dose-limiting toxicities were observed at 3 mg; however, two of two men enrolled at 6 mg experienced dose-limiting toxicities including thrombocytopenia and fever with grade 3 stomatitis. Adverse events observed at 3 mg included stomatitis, rash, ileus, and neutropenia. Pharmacodynamic studies showed tumor S6 phosphorylation inhibition in 50% of 10 evaluable rapamycin-treated men with sufficient paired tissue [median 58% inhibition (P = 0.049) versus 2% inhibition in controls (P = 0.75)] with no significant effect on AKT activity. We observed no change in Ki-67 or caspase-3 cleavage but noted a reduction in cytoplasmic p27 staining with increased nuclear localization with rapamycin treatment. Prostate tissue rapamycin concentrations were 3- to 4-fold higher than blood. CONCLUSIONS: At 3 mg daily, rapamycin successfully and safely inhibited prostate cancer S6 phosphorylation and achieved relatively high prostate tissue concentrations. No effect on AKT phosphorylation, tumor proliferation, or apoptosis was observed.

Authors
Armstrong, AJ; Netto, GJ; Rudek, MA; Halabi, S; Wood, DP; Creel, PA; Mundy, K; Davis, SL; Wang, T; Albadine, R; Schultz, L; Partin, AW; Jimeno, A; Fedor, H; Febbo, PG; George, DJ; Gurganus, R; De Marzo, AM; Carducci, MA
MLA Citation
Armstrong, AJ, Netto, GJ, Rudek, MA, Halabi, S, Wood, DP, Creel, PA, Mundy, K, Davis, SL, Wang, T, Albadine, R, Schultz, L, Partin, AW, Jimeno, A, Fedor, H, Febbo, PG, George, DJ, Gurganus, R, De Marzo, AM, and Carducci, MA. "A pharmacodynamic study of rapamycin in men with intermediate- to high-risk localized prostate cancer." Clin Cancer Res 16.11 (June 1, 2010): 3057-3066.
PMID
20501622
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
16
Issue
11
Publish Date
2010
Start Page
3057
End Page
3066
DOI
10.1158/1078-0432.CCR-10-0124

Impact of temsirolimus and anti-androgen therapy on circulating tumor cell (CTC) biology in men with castration-resistant metastatic prostate cancer (CRPC): A phase II study

Authors
Armstrong, AJ; Kemeny, G; Turnbull, JD; Chao, C; Winters, C; Fesko, YA; Bradley, DA; Halabi, S; George, DJ; Garcia-Blanco, M
MLA Citation
Armstrong, AJ, Kemeny, G, Turnbull, JD, Chao, C, Winters, C, Fesko, YA, Bradley, DA, Halabi, S, George, DJ, and Garcia-Blanco, M. "Impact of temsirolimus and anti-androgen therapy on circulating tumor cell (CTC) biology in men with castration-resistant metastatic prostate cancer (CRPC): A phase II study." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Serum lactate dehydrogenase (LDH) as a biomarker for survival with mTor inhibition in patients with metastatic renal cell carcinoma (RCC)

Authors
Armstrong, AJ; George, DJ; Halabi, S
MLA Citation
Armstrong, AJ, George, DJ, and Halabi, S. "Serum lactate dehydrogenase (LDH) as a biomarker for survival with mTor inhibition in patients with metastatic renal cell carcinoma (RCC)." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Use of progression-free survival (PFS) to predict overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC)

Authors
Halabi, S; Rini, BI; Stadler, WM; Small, EJ
MLA Citation
Halabi, S, Rini, BI, Stadler, WM, and Small, EJ. "Use of progression-free survival (PFS) to predict overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC)." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206.

PURPOSE: Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-alpha) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-alpha versus IFN-alpha monotherapy was conducted. PATIENTS AND METHODS: Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-alpha (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-alpha monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety. RESULTS: Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-alpha and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-alpha monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-alpha. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-alpha. Patients who developed HTN on bevacizumab plus IFN-alpha had a significantly improved PFS and OS versus patients without HTN. CONCLUSION: OS favored the bevacizumab plus IFN-alpha arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-alpha.

Authors
Rini, BI; Halabi, S; Rosenberg, JE; Stadler, WM; Vaena, DA; Archer, L; Atkins, JN; Picus, J; Czaykowski, P; Dutcher, J; Small, EJ
MLA Citation
Rini, BI, Halabi, S, Rosenberg, JE, Stadler, WM, Vaena, DA, Archer, L, Atkins, JN, Picus, J, Czaykowski, P, Dutcher, J, and Small, EJ. "Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206." J Clin Oncol 28.13 (May 1, 2010): 2137-2143.
PMID
20368558
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
13
Publish Date
2010
Start Page
2137
End Page
2143
DOI
10.1200/JCO.2009.26.5561

Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer.

A concurrent multicenter, randomized Phase II trial employing a recombinant poxviral vaccine provided evidence of enhanced median overall survival (OS) (p = 0.0061) in patients with metastatic castrate-resistant prostate cancer (mCRPC). The study reported here employed the identical vaccine in mCRPC to investigate the influence of GM-CSF with vaccine, and the influence of immunologic and prognostic factors on median OS. Thirty-two patients were vaccinated once with recombinant vaccinia containing the transgenes for prostate-specific antigen (PSA) and three costimulatory molecules. Patients received boosters with recombinant fowlpox containing the same four transgenes. Twelve of 32 patients showed declines in serum PSA post-vaccination and 2/12 showed decreases in index lesions. Median OS was 26.6 months (predicted median OS by the Halabi nomogram was 17.4 months). Patients with greater PSA-specific T-cell responses showed a trend (p = 0.055) toward enhanced survival. There was no difference in T-cell responses or survival in cohorts of patients receiving GM-CSF versus no GM-CSF. Patients with a Halabi predicted survival of <18 months (median predicted 12.3 months) had an actual median OS of 14.6 months, while those with a Halabi predicted survival of > or =18 months (median predicted survival 20.9 months) will meet or exceed 37.3 months, with 12/15 patients living longer than predicted (p = 0.035). Treg suppressive function was shown to decrease following vaccine in patients surviving longer than predicted, and increase in patients surviving less than predicted. This hypothesis-generating study provides evidence that patients with more indolent mCRPC (Halabi predicted survival > or =18 months) may best benefit from vaccine therapy.

Authors
Gulley, JL; Arlen, PM; Madan, RA; Tsang, K-Y; Pazdur, MP; Skarupa, L; Jones, JL; Poole, DJ; Higgins, JP; Hodge, JW; Cereda, V; Vergati, M; Steinberg, SM; Halabi, S; Jones, E; Chen, C; Parnes, H; Wright, JJ; Dahut, WL; Schlom, J
MLA Citation
Gulley, JL, Arlen, PM, Madan, RA, Tsang, K-Y, Pazdur, MP, Skarupa, L, Jones, JL, Poole, DJ, Higgins, JP, Hodge, JW, Cereda, V, Vergati, M, Steinberg, SM, Halabi, S, Jones, E, Chen, C, Parnes, H, Wright, JJ, Dahut, WL, and Schlom, J. "Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer." Cancer Immunol Immunother 59.5 (May 2010): 663-674.
PMID
19890632
Source
pubmed
Published In
Cancer Immunology, Immunotherapy
Volume
59
Issue
5
Publish Date
2010
Start Page
663
End Page
674
DOI
10.1007/s00262-009-0782-8

The importance of identifying and validating prognostic factors in oncology.

Prognosis plays a vital role in patient management and decision making. The assessment of prognostic factors, which relate baseline clinical and experimental covariables to outcomes, is one of the major objectives in clinical research. Historically, the impetus for the identification of prognostic factors has been the need to accurately estimate the effect of treatment adjusting for these variables. In oncology, the variability in outcome may be related to prognostic factors rather than to differences in treatments. In this article, we begin with a brief review of prognostic factors, and then subsequently offer a general discussion of their importance. Next, we describe the significance of study design before presenting various modeling approaches for identifying these factors and discussing the relative values of the different approaches. We illustrate the concepts within the framework of published and ongoing phase III trials in oncology.

Authors
Halabi, S; Owzar, K
MLA Citation
Halabi, S, and Owzar, K. "The importance of identifying and validating prognostic factors in oncology." Semin Oncol 37.2 (April 2010): e9-18. (Review)
PMID
20494694
Source
pubmed
Published In
Seminars in Oncology
Volume
37
Issue
2
Publish Date
2010
Start Page
e9
End Page
18
DOI
10.1053/j.seminoncol.2010.04.001

The COMPARE Registry: design and baseline patterns of care for men with biochemical failure after definitive treatment of localized prostate cancer.

OBJECTIVES: To define current standards of care for patients with prostate-specific antigen (PSA) failure after initial definitive local treatment of prostate cancer using Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry (COMPARE). This article describes the design of the COMPARE Registry, together with patient characteristics and prostate cancer management at enrolment. METHODS: The COMPARE Registry is a prospective, multicenter, observational study that collected data on patient characteristics, management practices, and outcomes of men presenting to their physician for the management of an increasing PSA level after definitive (surgical or radiotherapeutic) treatment of localized prostate cancer. Data collected by the physician and reported by the patient at the baseline (enrolment) visit are described. RESULTS: Between February 2004 and March 2007, 1120 men were enrolled at 150 sites throughout the United States. The men had a median age of 73 years (range, 46-95 years), were predominantly white (77%), and had a median PSA level of 7.9 ng/mL (range, 0-710.8 ng/mL) at diagnosis. Observation (74%) was the most common initial management choice at registry enrolment, and androgen-deprivation therapy (22%) was the most common initial treatment choice. CONCLUSIONS: Data from the COMPARE Registry should provide a valuable source of prospectively collected information on the contemporary management of prostate cancer and patient outcomes after PSA failure.

Authors
Sartor, O; McLeod, DG; Halabi, S; Schellhammer, PF; Scardino, PT; D'Amico, AV; Bennett, C; Wei, JT; COMPARE Registry Steering Committee,
MLA Citation
Sartor, O, McLeod, DG, Halabi, S, Schellhammer, PF, Scardino, PT, D'Amico, AV, Bennett, C, Wei, JT, and COMPARE Registry Steering Committee, . "The COMPARE Registry: design and baseline patterns of care for men with biochemical failure after definitive treatment of localized prostate cancer." Urology 75.3 (March 2010): 623-629.
PMID
19589569
Source
pubmed
Published In
Urology
Volume
75
Issue
3
Publish Date
2010
Start Page
623
End Page
629
DOI
10.1016/j.urology.2009.04.059

Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials.

BACKGROUND: Docetaxel is associated with prolonged survival in castration-resistant prostate cancer (CRPC). Platinum compounds have modest but distinct single-agent activity. Carboplatin may have greatest potential for benefit when combined with taxanes. We investigated whether there is a subset of patients with CRPC for whom the efficacy of combination taxane-estramustine-carboplatin (TEC) chemotherapy may be greatest. PATIENTS AND METHODS: Individual patient data (n = 310) were obtained from seven trials using TEC chemotherapy. Prostate-specific antigen (PSA) response was defined as > or = 50% post-therapy decline from baseline. Overall survival was defined from baseline to death from any cause. Logistic and Cox regression were used to investigate heterogeneity in outcome to TEC by patient and disease characteristics. Predicted survival probabilities were calculated from the Halabi Cancer and Leukemia Group B (CALGB) nomogram. RESULTS: The pooled PSA response proportion was 69% [95% confidence interval (CI) 56% to 80%]. There was no evidence of differential PSA response by disease characteristics. Established prognostic factors were associated with survival. The pooled 12-month survival estimate of 79% (95% CI 71% to 84%) was higher than the median 59% 12-month nomogram-predicted survival. CONCLUSIONS: TEC chemotherapy has significant clinical activity in CRPC. A randomized, controlled trial evaluating the addition of carboplatin to taxane-based chemotherapy is needed to elucidate the value of carboplatin in CRPC.

Authors
Regan, MM; O'Donnell, EK; Kelly, WK; Halabi, S; Berry, W; Urakami, S; Kikuno, N; Oh, WK
MLA Citation
Regan, MM, O'Donnell, EK, Kelly, WK, Halabi, S, Berry, W, Urakami, S, Kikuno, N, and Oh, WK. "Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials." Ann Oncol 21.2 (February 2010): 312-318.
PMID
19633053
Source
pubmed
Published In
Annals of Oncology
Volume
21
Issue
2
Publish Date
2010
Start Page
312
End Page
318
DOI
10.1093/annonc/mdp308

The development of risk groups in men with metastatic castration-resistant prostate cancer based on risk factors for PSA decline and survival.

AIMS OF THE STUDY: There are no known predictive factors of response in men receiving chemotherapy for metastatic castration-resistant prostate cancer (mCRPC). We investigated pre-treatment factors that predicted a 30% PSA decline (30% PSAD) within 3 months of starting chemotherapy, and assessed performance of a risk group classification in predicting PSA declines and overall survival (OS) in men with mCRPC. METHODS: In TAX327, 1006 men with mCRPC were randomized to receive docetaxel (D) in two schedules, or mitoxantrone (M), each with prednisone: 989 provided data on PSA decline within 3 months. Predictive factors for a 30% PSAD were identified using multivariable regression in D-treated men (n=656) and validated in M-treated men (n=333). RESULTS: Four independent risk factors predicted 30% PSAD: pain, visceral metastases, anaemia and bone scan progression. Risk groups (good: 0-1 factors, intermediate: 2 factors and poor: 3-4 factors) were developed with median OS of 25.7, 18.7 and 12.8 months (p<0.0001); 30% PSAD in 78%, 66% and 58% of men (p<0.001); and measurable disease response in 19%, 9% and 5% of men (p=0.018), respectively. In the validation cohort, similar predictive ability was noted for 30% PSAD, tumour response and OS. PCWG2 subtypes were also predictive but resulted in unequal grouping. C-indices were 0.59 and 0.62 for 30% PSAD and OS in the validation dataset, respectively. CONCLUSIONS: Risk groups have been identified and validated that predict PSAD and OS in men with mCRPC and may facilitate evaluation of new systemic regimens warranting definitive testing in comparison with docetaxel and prednisone. Prospective validation of this classification system is needed.

Authors
Armstrong, AJ; Tannock, IF; de Wit, R; George, DJ; Eisenberger, M; Halabi, S
MLA Citation
Armstrong, AJ, Tannock, IF, de Wit, R, George, DJ, Eisenberger, M, and Halabi, S. "The development of risk groups in men with metastatic castration-resistant prostate cancer based on risk factors for PSA decline and survival." Eur J Cancer 46.3 (February 2010): 517-525.
PMID
20005697
Source
pubmed
Published In
European Journal of Cancer
Volume
46
Issue
3
Publish Date
2010
Start Page
517
End Page
525
DOI
10.1016/j.ejca.2009.11.007

Arsenic trioxide in recurrent urothelial cancer: a cancer and leukemia group B phase II trial (CALGB 99903).

BACKGROUND: Arsenic trioxide is highly active in patients with acute promyelocytic leukemia. There are also preclinical data to suggest that this drug might be active in nonhematopoietic malignancies, and transitional cell carcinoma cell lines are particularly sensitive to this agent. PATIENTS AND METHODS: Twelve evaluable patients with metastatic urothelial cancer were treated with arsenic trioxide in a phase II trial conducted by the Cancer and Leukemia Group B. Eligible patients were required to have measurable urothelial cancer and a maximum of 1 previous chemotherapy regimen. Arsenic trioxide was given at a dose of 0.3 mg/kg daily for 5 days every 28 days. RESULTS: No major responses were observed; 4 patients achieved stable disease. The median survival was 6.5 months (95% CI, 3.9-13.4 months). The most commonly observed toxicities included fatigue and malaise, anemia, nausea, emesis, and constipation. CONCLUSION: Arsenic trioxide at this dose and schedule does not have significant activity in previously treated urothelial cancer and has substantial toxicity in this patient population.

Authors
Bajorin, DF; Halabi, S; Small, E
MLA Citation
Bajorin, DF, Halabi, S, and Small, E. "Arsenic trioxide in recurrent urothelial cancer: a cancer and leukemia group B phase II trial (CALGB 99903)." Clin Genitourin Cancer 7.3 (October 2009): E66-E70.
PMID
19815484
Source
pubmed
Published In
Clinical genitourinary cancer
Volume
7
Issue
3
Publish Date
2009
Start Page
E66
End Page
E70
DOI
10.3816/CGC.2009.n.026

Management of kidney cancer: Canadian Kidney Cancer Forum Consensus Update (vol 3, pg 200, 2009)

Authors
Rini, BI; Halabi, S; Rosenberg, JE; Escudier, B; Pluzanska, A; Koralewski, P; Hotte, S
MLA Citation
Rini, BI, Halabi, S, Rosenberg, JE, Escudier, B, Pluzanska, A, Koralewski, P, and Hotte, S. "Management of kidney cancer: Canadian Kidney Cancer Forum Consensus Update (vol 3, pg 200, 2009)." CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL 3.4 (August 2009): 289-289.
Source
wos-lite
Published In
Canadian Urological Association journal = Journal de l'Association des urologues du Canada
Volume
3
Issue
4
Publish Date
2009
Start Page
289
End Page
289

Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer.

PURPOSE: To explore whether progression-free survival (PFS) or biochemical PFS can be used as a predictor of overall survival (OS) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer. PATIENTS AND METHODS: Data from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled. Men were eligible if they had prostate cancer that had progressed during androgen deprivation therapy and did not receive prior treatment with chemotherapy, immunotherapy, or other nonhormonal therapy. Landmark analyses of PFS at 3 and 6 months from randomization/registration were performed to minimize lead time bias. The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS. In addition, biochemical progression using the definitions of Prostate-Specific Antigen Working Group (PSAW) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS. RESULTS: The median survival time among men who experienced progression at 3 months was 9.2 months (95% CI, 8.0 to 10.0 months) compared with 17.8 months in men who did not experience progression at 3 months (95% CI, 16.2 to 20.4 months; P < .0001). Compared with men who did not progress at 3 and at 6 months, the adjusted hazard ratios for death were 2.0 (95% CI, 1.7 to 2.4; P < .001) and 1.9 (95% CI, 1.6 to 2.4; P < .001) for men who experienced progression at 3 and 6 months, respectively. In addition, biochemical progression at 3 months predicted OS. The association between PFS and OS was 0.30 (95% confidence limits = 0.26, 0.32). CONCLUSION: PFS at 3 and 6 months and biochemical progression at 3 months predict OS. These observations require prospective validation.

Authors
Halabi, S; Vogelzang, NJ; Ou, S-S; Owzar, K; Archer, L; Small, EJ
MLA Citation
Halabi, S, Vogelzang, NJ, Ou, S-S, Owzar, K, Archer, L, and Small, EJ. "Progression-free survival as a predictor of overall survival in men with castrate-resistant prostate cancer." J Clin Oncol 27.17 (June 10, 2009): 2766-2771.
PMID
19380448
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
17
Publish Date
2009
Start Page
2766
End Page
2771
DOI
10.1200/JCO.2008.18.9159

A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102.

BACKGROUND: This phase II trial (Cancer and Leukemia Group B 90102) sought to determine the efficacy of cisplatin, standard infusion of gemcitabine and gefitinib in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: Eligible patients had previously untreated measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of zero to two and creatinine clearance >50 ml/min. Treatment consisted of cisplatin 70 mg/m(2) day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8 given every 3 weeks concurrent with gefitinib 500 mg/day orally for six cycles. Maintenance gefitinib 500 mg/day was continued for responding or stable disease. RESULTS: Fifty-four of 58 patients were assessable. Twelve patients (22%) had node-only disease, and 25 (46%) had an ECOG performance status of zero. There were 23 objective responses for an overall response rate of 42.6% [95% confidence interval (CI) 29.2% to 56.8%]. The median survival time was 15.1 months (95% CI 11.1-21.7 months) and the median time to progression was 7.4 months (95% CI 5.6-9.2 months). CONCLUSIONS: The combination of cisplatin, gemcitabine and gefitinib is well tolerated and active in advanced transitional cell carcinoma. The addition of gefitinib does not appear to improve response rate or survival in comparison to historical controls of cisplatin and gemcitabine alone.

Authors
Philips, GK; Halabi, S; Sanford, BL; Bajorin, D; Small, EJ; Cancer and Leukemia Group B,
MLA Citation
Philips, GK, Halabi, S, Sanford, BL, Bajorin, D, Small, EJ, and Cancer and Leukemia Group B, . "A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102." Ann Oncol 20.6 (June 2009): 1074-1079.
PMID
19168670
Source
pubmed
Published In
Annals of Oncology
Volume
20
Issue
6
Publish Date
2009
Start Page
1074
End Page
1079
DOI
10.1093/annonc/mdn749

PATIENT SATISFACTION WITH OBSERVATION OR HORMONAL THERAPY AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) AFTER BIOCHEMICAL FAILURE IN MEN WITH PROSTATE CANCER: RESULTS FROM THE COMPARE REGISTRY

Authors
Bennett, CL; Sartor, O; Halabi, S; Comm, COMPARER
MLA Citation
Bennett, CL, Sartor, O, Halabi, S, and Comm, COMPARER. "PATIENT SATISFACTION WITH OBSERVATION OR HORMONAL THERAPY AND HEALTH-RELATED QUALITY OF LIFE (HRQOL) AFTER BIOCHEMICAL FAILURE IN MEN WITH PROSTATE CANCER: RESULTS FROM THE COMPARE REGISTRY." JOURNAL OF UROLOGY 181.4 (April 2009): 90-90.
Source
wos-lite
Published In
The Journal of Urology
Volume
181
Issue
4
Publish Date
2009
Start Page
90
End Page
90

Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials.

BACKGROUND: Multiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups. METHODS: We combined data from all randomized double-blind placebo-controlled trials that evaluated aspirin for the prevention of colorectal adenomas. We used random-effects meta-analysis to estimate risk ratios and 95% confidence intervals (CIs) for the effect of aspirin on the occurrence of adenomas and of advanced lesions (ie, tubulovillous adenomas, villous adenomas, adenomas >or=1 cm in diameter, adenomas with high-grade dysplasia, or invasive cancer). All statistical tests were two-sided. RESULTS: We identified four clinical trials with 2967 randomly assigned participants. Each trial evaluated aspirin for the secondary prevention of colorectal adenomas. Doses of aspirin tested ranged from 81 to 325 mg/d. The average age of participants at baseline was 58 years, and 60% were male. Median follow-up was 33 months. A total of 2698 participants underwent colonoscopic follow-up and were included in the analysis of adenoma occurrence and advanced-lesion occurrence after randomization. Among these participants, adenomas were found in 424 (37%) of the 1156 participants allocated to placebo and in 507 (33%) of the 1542 participants allocated to any dose of aspirin. Advanced lesions were found in 12% of participants in the placebo group and in 9% of participants allocated to any dose of aspirin. The pooled risk ratio of any adenoma for any dose of aspirin vs placebo was 0.83 (95% CI = 0.72 to 0.96). This corresponded to an absolute risk reduction of 6.7% (95% CI = 3.2% to 10.2%). For any advanced lesion, the pooled risk ratio was 0.72 (95% CI = 0.57 to 0.90). We found no statistically significant effect modification for any of the baseline factors studied. CONCLUSION: Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.

Authors
Cole, BF; Logan, RF; Halabi, S; Benamouzig, R; Sandler, RS; Grainge, MJ; Chaussade, S; Baron, JA
MLA Citation
Cole, BF, Logan, RF, Halabi, S, Benamouzig, R, Sandler, RS, Grainge, MJ, Chaussade, S, and Baron, JA. "Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials." J Natl Cancer Inst 101.4 (February 18, 2009): 256-266.
PMID
19211452
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
101
Issue
4
Publish Date
2009
Start Page
256
End Page
266
DOI
10.1093/jnci/djn485

The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer.

The purpose of this study was to evaluate the relationship of baseline body mass index (BMI) and serum testosterone level with prostate cancer outcomes in men with castration-resistant metastatic prostate cancer (CRPC). BMI and testosterone levels were evaluated for their ability to predict overall survival (OS) and prostate-specific antigen (PSA) declines in the TAX327 clinical trial, an international phase III randomized trial of one of the two schedules of docetaxel and prednisone compared with mitoxantrone and prednisone. In this study of 1006 men with CRPC, the median serum testosterone level was 14.5 ng per 100 ml (range 0-270), the median BMI was 27 kg m(-2) (range 15.7-46.5), and 26% of men were obese or morbidly obese (BMI>or=30). Obesity was associated with younger age, lower PSA and alkaline phosphatase levels, and higher performance status, primary Gleason sum, testosterone and hemoglobin compared to absence of obesity. In multivariate analysis, neither BMI, presence of obesity, nor baseline testosterone was significantly associated with OS or PSA declines. Higher testosterone levels among obese men suggest incomplete gonadal suppression with current therapies, but these differences may not be clinically relevant in men with CRPC. There was evidence of potential hemodilution of PSA and alkaline phosphatase levels in obese men.

Authors
Armstrong, AJ; Halabi, S; de Wit, R; Tannock, IF; Eisenberger, M
MLA Citation
Armstrong, AJ, Halabi, S, de Wit, R, Tannock, IF, and Eisenberger, M. "The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer." Prostate Cancer Prostatic Dis 12.1 (2009): 88-93.
PMID
18574490
Source
pubmed
Published In
Prostate Cancer and Prostatic Diseases
Volume
12
Issue
1
Publish Date
2009
Start Page
88
End Page
93
DOI
10.1038/pcan.2008.36

Treatment Decisions for Advanced Genitourinary Cancers: From Symptoms to Risk Assessment

Context: Current and emerging treatment options for advanced prostate, renal, and bladder cancer were discussed at the annual Interactive Genitourinary Cancer Conference (IGUCC) held in February 2009 in connection with the 2nd World Congress on Controversies in Urology (CURy). Objective: To provide practical clinical guidance for physicians and to promote the implementation of recent advances in the management of genitourinary cancers through closer collaboration among urologists, medical oncologists, and radiation oncologists. Evidence acquisition: This article was developed from presentations given at IGUCC 2009. Evidence synthesis: Docetaxel treatment is established as the standard first-line treatment for patients with metastatic castrate-resistant prostate cancer (mCRPC), based on improvements in overall survival regardless of age, performance status, and pain. Treatment should be introduced according to risk-factor assessment, clinical status, and patient values and preferences. Similarly, management of senior adults with mCRPC should be individually adapted to the patient's health status rather than chronologic age, especially since the benefits and toxicity associated with docetaxel treatment are similar in senior adults and younger patients. Asymptomatic patients with adverse prognostic factors for survival such as visceral metastases, anaemia, and new bone lesions may be candidates for chemotherapy. Prognostic nomograms based on pretreatment parameters aid in identifying patients for earlier chemotherapy. Second-line treatments for CRPC patients are needed, but currently no agent has demonstrated efficacy in phase 3 clinical trials. For patients with a prior response to docetaxel, retreatment at relapse can be effective and well tolerated. There is a strong rationale for targeting angiogenesis in renal cell carcinoma (RCC), and new targeted therapies have changed treatment paradigms for RCC. In contrast, little progress has been made in the treatment of advanced bladder cancer since the introduction of cisplatin-based chemotherapy; new strategies are needed. Conclusions: Docetaxel (every 3 wk) treatment is a therapeutic option in elderly and asymptomatic mCRPC patients. Docetaxel retreatment is effective in initial responders. © 2009 European Association of Urology.

Authors
Fitzpatrick, JM; Sternberg, CN; Saad, F; Extermann, M; Caffo, O; Halabi, S; Kramer, G; Oudard, S; Wit, RD
MLA Citation
Fitzpatrick, JM, Sternberg, CN, Saad, F, Extermann, M, Caffo, O, Halabi, S, Kramer, G, Oudard, S, and Wit, RD. "Treatment Decisions for Advanced Genitourinary Cancers: From Symptoms to Risk Assessment." European Urology, Supplements 8.9 (2009): 738-746.
Source
scival
Published In
European Urology Supplements
Volume
8
Issue
9
Publish Date
2009
Start Page
738
End Page
746
DOI
10.1016/j.eursup.2009.06.001

Use of nonsteroidal antiinflammatory drugs and distal large bowel cancer in whites and African Americans.

Despite the belief that the etiology of and risk factors for rectal cancer might differ from those for colon cancer, relatively few studies have examined rectal cancer in relation to use of nonsteroidal antiinflammatory drugs (NSAIDs). The authors evaluated the association between NSAIDs and distal large bowel cancer in African Americans and whites, using data from a population-based case-control study of 1,057 incident cases of adenocarcinoma of the sigmoid colon, rectosigmoid junction, and rectum and 1,019 controls from North Carolina (2001-2006). NSAID use was inversely associated with distal large bowel cancer in whites (odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.46, 0.79). The inverse association was evident for all types of NSAIDs but was slightly stronger with prescription NSAIDs, particularly selective cyclooxygenase 2 inhibitors (OR = 0.38, 95% CI: 0.25, 0.56). Compared with whites, a relatively weak inverse association was found in African Americans (OR = 0.87, 95% CI: 0.55, 1.40), although odds ratio heterogeneity by race could not be confirmed (P = 0.21). In addition, the strength of the association with NSAIDs varied by tumor location, suggesting more potent effects for rectal and rectosigmoid cancers than for sigmoid cancer. The chemopreventive potential of NSAIDs might differ by population and by tumor characteristics.

Authors
Kim, S; Martin, C; Galanko, J; Woosley, JT; Schroeder, JC; Keku, TO; Satia, JA; Halabi, S; Sandler, RS
MLA Citation
Kim, S, Martin, C, Galanko, J, Woosley, JT, Schroeder, JC, Keku, TO, Satia, JA, Halabi, S, and Sandler, RS. "Use of nonsteroidal antiinflammatory drugs and distal large bowel cancer in whites and African Americans." Am J Epidemiol 168.11 (December 1, 2008): 1292-1300.
PMID
18945689
Source
pubmed
Published In
American Journal of Epidemiology
Volume
168
Issue
11
Publish Date
2008
Start Page
1292
End Page
1300
DOI
10.1093/aje/kwn255

Multicenter phase 2 study of neoadjuvant paclitaxel, estramustine phosphate, and carboplatin plus androgen deprivation before radiation therapy in patients with unfavorable-risk localized prostate cancer: results of Cancer and Leukemia Group B 99811.

BACKGROUND: A multicenter phase 2 trial was conducted to evaluate the safety and feasibility of radiotherapy after paclitaxel, estramustine phosphate, and carboplatin (TEC) plus androgen deprivation therapy in previously untreated unfavorable-risk localized prostate cancer patients. METHODS: Patients with localized high-risk prostate cancer were treated with 4 cycles (16 weeks) of continuous weekly paclitaxel at 80 mg/m(2) intravenously with estramustine at 280 mg orally 3 times a day for 5 days a week and carboplatin (area under the curve of 6) on Day 1 of every cycle followed by 3-dimensional conformal or intensity-modulated radiotherapy (total dose of 77.4 gray [Gy] in 1.8-Gy fractions). All patients received androgen deprivation therapy with either goserelin acetate at 3.6 mg subcutaneously or leuprolide acetate at 7.5 mg intramuscularly monthly for 6 months starting at Day 1 of therapy. Patients were evaluated for acute and late toxicities along with progression-free survival and time to prostate-specific antigen (PSA) failure associated with the multimodality therapy. RESULTS: Twenty-seven of 34 patients completed therapy and were evaluable for safety and feasibility. There was 1 patient with grade 3 nausea during chemotherapy. No other grade 3 or 4 gastrointestinal, cardiovascular, or genitourinary acute or late toxicities were reported. The most common grade 1 to 2 late toxicities were proctitis (11%), dysuria (11%), and urinary frequency/urgency (33%). Two deaths due to prostate cancer were observed. Median follow-up was 38 months among 24 surviving patients; median PSA progression-free survival was 12.1 months (95% confidence interval, 13.3-25.9). CONCLUSIONS: Neoadjuvant chemohormonal therapy with TEC followed by high-dose radiation therapy is safe and feasible in a multicenter setting.

Authors
Kelly, WK; Halabi, S; Elfiky, A; Ou, S-S; Bogart, J; Zelefsky, M; Small, E; Cancer Leukemia Group B,
MLA Citation
Kelly, WK, Halabi, S, Elfiky, A, Ou, S-S, Bogart, J, Zelefsky, M, Small, E, and Cancer Leukemia Group B, . "Multicenter phase 2 study of neoadjuvant paclitaxel, estramustine phosphate, and carboplatin plus androgen deprivation before radiation therapy in patients with unfavorable-risk localized prostate cancer: results of Cancer and Leukemia Group B 99811." Cancer 113.11 (December 1, 2008): 3137-3145.
PMID
18989865
Source
pubmed
Published In
Cancer
Volume
113
Issue
11
Publish Date
2008
Start Page
3137
End Page
3145
DOI
10.1002/cncr.23910

Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206.

PURPOSE: Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted. PATIENTS AND METHODS: Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%). CONCLUSION: Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.

Authors
Rini, BI; Halabi, S; Rosenberg, JE; Stadler, WM; Vaena, DA; Ou, S-S; Archer, L; Atkins, JN; Picus, J; Czaykowski, P; Dutcher, J; Small, EJ
MLA Citation
Rini, BI, Halabi, S, Rosenberg, JE, Stadler, WM, Vaena, DA, Ou, S-S, Archer, L, Atkins, JN, Picus, J, Czaykowski, P, Dutcher, J, and Small, EJ. "Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206." J Clin Oncol 26.33 (November 20, 2008): 5422-5428.
PMID
18936475
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
33
Publish Date
2008
Start Page
5422
End Page
5428
DOI
10.1200/JCO.2008.16.9847

Combination external beam radiation and brachytherapy boost with androgen suppression for treatment of intermediate-risk prostate cancer: an initial report of CALGB 99809.

PURPOSE: Transperineal prostate brachytherapy (TPPB) can be used with external beam radiation therapy (EBRT) to provide a high-dose conformal boost to the prostate. The results of a multicenter Phase II trial assessing safety of combination of EBRT and TPPB boost with androgen suppression (AST) in treatment of intermediate-risk prostate cancer are present here. MATERIALS AND METHODS: Patients had intermediate-risk prostate cancer. Six months of AST was administered. EBRT to the prostate and seminal vesicles was administered to 45Gy followed by TPPB using either (125)I or (103)Pd to deliver an additional 100Gy or 90Gy. Toxicity was graded using the National Cancer Institute CTC version 2 and the Radiation Therapy Oncology Group late radiation morbidity scoring systems. RESULTS: Sixty-three patients were enrolled. Median follow-up was 38 months. Side effects of AST including sexual dysfunction and vasomotor symptoms were commonly observed. Apart from erectile dysfunction, short-term Grade 2 and 3 toxicity was noted in 21% and 7%, primarily genitourinary related. Long-term Grade 2 and 3 toxicities were noted in 13% and 3%. Two patients had Grade 3 dysuria that resolved with longer follow-up. The most common Grade 2 long-term toxicity was urinary frequency (5%). No biochemical or clinical evidence of progression was noted for the entire cohort. CONCLUSIONS: In a cooperative group setting, combination EBRT and TPPB boost with 6 months of AST was generally well tolerated with expected genitourinary and gastrointestinal toxicities. Further follow-up will be required to fully assess long-term toxicity and cancer control.

Authors
Hurwitz, MD; Halabi, S; Ou, S-S; McGinnis, LS; Keuttel, MR; Dibiase, SJ; Small, EJ
MLA Citation
Hurwitz, MD, Halabi, S, Ou, S-S, McGinnis, LS, Keuttel, MR, Dibiase, SJ, and Small, EJ. "Combination external beam radiation and brachytherapy boost with androgen suppression for treatment of intermediate-risk prostate cancer: an initial report of CALGB 99809." Int J Radiat Oncol Biol Phys 72.3 (November 1, 2008): 814-819.
PMID
18407435
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
72
Issue
3
Publish Date
2008
Start Page
814
End Page
819
DOI
10.1016/j.ijrobp.2008.01.010

Flexible Frames and Control Sampling in Case-Control Studies: Weighters (Survey Statisticians) Versus Anti-Weighters (Epidemiologists).

We propose two innovations in statistical sampling for controls to enable better design of population-based case-control studies. The main innovation leads to novel solutions, without using weights, of the difficult and long-standing problem of selecting a control from persons in a household. Another advance concerns the drawing (at the outset) of the households themselves and involves random-digit dialing with atypical use of list-assisted sampling. A common element throughout is that one capitalizes on flexibility (not broadly available in usual survey settings) in choosing the frame, which specifies the population of persons from which both cases and controls come.

Authors
Potthoff, RF; Halabi, S; Schildkraut, JM; Newman, B
MLA Citation
Potthoff, RF, Halabi, S, Schildkraut, JM, and Newman, B. "Flexible Frames and Control Sampling in Case-Control Studies: Weighters (Survey Statisticians) Versus Anti-Weighters (Epidemiologists)." Am Stat 62.4 (November 1, 2008): 307-313.
PMID
19759839
Source
pubmed
Published In
The American statistician
Volume
62
Issue
4
Publish Date
2008
Start Page
307
End Page
313
DOI
10.1198/000313008X364525

A phase II study of estramustine, docetaxel, and exisulind in patients with hormone- refractory prostate cancer: results of cancer and leukemia group B trial 90004.

PURPOSE: Docetaxel/estramustine is a known active regimen in hormonerefractory prostate cancer (HRPC). A phase II study was conducted to assess the safety and efficacy of docetaxel/estramustine combined with exisulind, an apoptotic antineoplastic drug. PATIENTS AND METHODS: Eighty men with chemotherapy-naive HRPC were enrolled in a multicenter, cooperative group study. The treatment regimen consisted of oral estramustine (280 mg 3 times daily for 5 days), docetaxel 70 mg/m2, oral exisulind (250 mg twice daily), oral dexamethasone (8 mg twice daily for 3 days), and oral warfarin (2 mg daily). RESULTS: Seventy-five eligible patients were treated with a median of 6 cycles of therapy. Fortyseven patients (62.7%; 95% CI, 50.7%-73.6%) had a > or = 50% decline in prostate-specific antigen levels. Forty-six patients had measurable disease with 6 partial responses (13%; 95% CI, 4.9%-26.3%). The main grade 3/4 toxicities were neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time to first progression was 5.1 months (95% CI, 4.4-6.3 months) and the median survival time was 17.8 months (95% CI, 14.7-20.1 months). CONCLUSION: The combination of estramustine/docetaxel/exisulind was associated with significant thomboembolic toxicity despite prophylactic warfarin. The contribution of exisulind to toxicity is uncertain. Prostate-specific antigen decline, response rates, and progression-free and overall survival are similar to those reported with docetaxel/estramustine.

Authors
Dawson, NA; Halabi, S; Ou, S-S; Biggs, DD; Kessinger, A; Vogelzang, N; Clamon, GH; Nanus, DM; Kelly, WK; Small, EJ; Cancer And Leukemia Group B,
MLA Citation
Dawson, NA, Halabi, S, Ou, S-S, Biggs, DD, Kessinger, A, Vogelzang, N, Clamon, GH, Nanus, DM, Kelly, WK, Small, EJ, and Cancer And Leukemia Group B, . "A phase II study of estramustine, docetaxel, and exisulind in patients with hormone- refractory prostate cancer: results of cancer and leukemia group B trial 90004." Clin Genitourin Cancer 6.2 (September 2008): 110-116.
PMID
18824434
Source
pubmed
Published In
Clinical genitourinary cancer
Volume
6
Issue
2
Publish Date
2008
Start Page
110
End Page
116
DOI
10.3816/CGC.2008.n.017

Pain predicts overall survival in men with metastatic castration-refractory prostate cancer.

PURPOSE: Pain from castration-refractory prostate cancer (CRPC) bone metastases is a common event. Although it is assumed that pain represents an adverse prognostic factor, this variable has not been extensively evaluated. The objective of this study was to determine whether men with CRPC who had higher pain interference scores at baseline had worse clinical outcomes compared with men who had lower pain scores. PATIENTS AND METHODS: Data from three randomized phase III multicenter trials conducted by the Cancer and Leukemia Group B from 1992 to 1998 were combined. Eligible patients had progressive CRPC adenocarcinoma of the prostate, an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic functions. Seven items from the Brief Pain Inventory were used to assess the impact of pain on a range of daily activities and quality of life, each rated on a scale from 0 to 10. RESULTS: In 599 men, the median pain interference scores was 17 (interquartile range, 4 to 34), and 38% of the men had opioid analgesic use at baseline. There was a statistically significant association between pain interference scores and risk of death. The median survival times were 17.6 months (95% CI, 16.1 to 19.1 months) and 10.2 months (95% CI, 8.6 to 11.3 months; P < .001) in men with low (< 17) and high (>or= 17) pain scores, respectively. Pain was inversely associated with likelihood of prostate-specific antigen decline, objective response, and time to bone progression. CONCLUSION: This analysis demonstrates that pain is a statistically significant predictor of overall survival in men with metastatic CRPC. These results need to be validated prospectively in future phase III trials.

Authors
Halabi, S; Vogelzang, NJ; Kornblith, AB; Ou, S-S; Kantoff, PW; Dawson, NA; Small, EJ
MLA Citation
Halabi, S, Vogelzang, NJ, Kornblith, AB, Ou, S-S, Kantoff, PW, Dawson, NA, and Small, EJ. "Pain predicts overall survival in men with metastatic castration-refractory prostate cancer." J Clin Oncol 26.15 (May 20, 2008): 2544-2549.
PMID
18487572
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008
Start Page
2544
End Page
2549
DOI
10.1200/JCO.2007.15.0367

The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer

Authors
Armstrong, AJ; Halabi, S; Tannock, IF; Ronald, D; Eisenberger, MA
MLA Citation
Armstrong, AJ, Halabi, S, Tannock, IF, Ronald, D, and Eisenberger, MA. "The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure (OF) due to adjuvant chemotherapy (AdC): First results from CALGB trial 7980

Authors
Shapiro, CL; Halabi, S; Gibson, G; Weckstein, DJ; Kirshner, J; Sikov, WM; Winer, EP; Hudis, CA; Isaacs, C; Weckstein, D; Schilsky, RL; Paskett, E
MLA Citation
Shapiro, CL, Halabi, S, Gibson, G, Weckstein, DJ, Kirshner, J, Sikov, WM, Winer, EP, Hudis, CA, Isaacs, C, Weckstein, D, Schilsky, RL, and Paskett, E. "Effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure (OF) due to adjuvant chemotherapy (AdC): First results from CALGB trial 7980." JOURNAL OF CLINICAL ONCOLOGY 26.15 (May 20, 2008).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
26
Issue
15
Publish Date
2008

Tumor volume changes on 1.5 tesla endorectal MRI during neoadjuvant androgen suppression therapy for higher-risk prostate cancer and recurrence in men treated using radiation therapy results of the phase II CALGB 9682 study.

PURPOSE: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. PATIENTS AND METHODS: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). RESULTS: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. CONCLUSION: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST.

Authors
D'Amico, AV; Halabi, S; Tempany, C; Titelbaum, D; Philips, GK; Loffredo, M; McMahon, E; Sanford, B; Vogelzang, NJ; Small, EJ; Cancer and Leukemia Group B,
MLA Citation
D'Amico, AV, Halabi, S, Tempany, C, Titelbaum, D, Philips, GK, Loffredo, M, McMahon, E, Sanford, B, Vogelzang, NJ, Small, EJ, and Cancer and Leukemia Group B, . "Tumor volume changes on 1.5 tesla endorectal MRI during neoadjuvant androgen suppression therapy for higher-risk prostate cancer and recurrence in men treated using radiation therapy results of the phase II CALGB 9682 study." Int J Radiat Oncol Biol Phys 71.1 (May 1, 2008): 9-15.
PMID
18037582
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
71
Issue
1
Publish Date
2008
Start Page
9
End Page
15
DOI
10.1016/j.ijrobp.2007.09.033

Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women.

Ovarian cancer is most frequently diagnosed in postmenopausal women; however, the strongest risk predictors, pregnancy and oral contraceptive use, occur in most women in their twenties and thirties. Relatively few studies have examined how reproductive risk factors vary between pre- and postmenopausal ovarian cancer. The authors used data from a population-based, case-control study of ovarian cancer (896 cases, 967 controls) conducted in North Carolina from 1999 to 2006. Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Inverse associations with ovarian cancer were observed with duration of oral contraceptive use, later age at last use, and more recent use among premenopausal women; no significant associations were found for postmenopausal women. Analyses limited to oral contraceptive users showed that duration was a more significant predictor of risk than was timing of use. Parity was inversely associated with premenopausal but not postmenopausal ovarian cancer. Later age at pregnancy was associated with reduced risk for both pre- and postmenopausal women. Analyses among parous women showed that pregnancy timing was a stronger risk predictor than number of pregnancies. Findings suggest that associations between ovarian cancer and reproductive characteristics vary by menopausal status. Additional research is needed to further elucidate risk factors for postmenopausal disease.

Authors
Moorman, PG; Calingaert, B; Palmieri, RT; Iversen, ES; Bentley, RC; Halabi, S; Berchuck, A; Schildkraut, JM
MLA Citation
Moorman, PG, Calingaert, B, Palmieri, RT, Iversen, ES, Bentley, RC, Halabi, S, Berchuck, A, and Schildkraut, JM. "Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women." Am J Epidemiol 167.9 (May 1, 2008): 1059-1069.
PMID
18303003
Source
pubmed
Published In
American Journal of Epidemiology
Volume
167
Issue
9
Publish Date
2008
Start Page
1059
End Page
1069
DOI
10.1093/aje/kwn006

Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207.

BACKGROUND: There is no standard second-line treatment for advanced urothelial carcinoma (UC). Response rates to second-line chemotherapy for advanced UC are low and response duration is short. Bortezomib is a proteasome inhibitor with preclinical activity against UC. PATIENTS AND METHODS: Treatment consisted of bortezomib 1.3 mg/m(2) i.v. twice weekly for two consecutive weeks, followed by a 1-week break. The primary end point was objective response rate (complete response + partial response) by Response Evaluation Criteria in Solid Tumors criteria. Secondary end points included safety, toxicity, and progression-free and overall survival. RESULTS: In all, 25 patients with advanced UC previously treated with combination chemotherapy were enrolled in a multi-institutional single-arm trial from December 2003 through April 2005. Only 29% of patients had node-only metastases. Grade 3/4 drug-related toxic effects included thrombocytopenia (4%), anemia (8%), lymphopenia (8%), sensory neuropathy (6%), hyperglycemia (4%), hypernatremia (4%), fatigue (4%), neuropathic pain (6%), dehydration (4%), and vomiting (4%). No objective responses were observed [95% confidence interval (CI) = 0-12]. The median time to progression was 1.4 months (95% CI = 1.1-2.0 months), and the median survival time was 5.7 months (95% CI = 3.6-8.4 months). There were no treatment-related deaths. CONCLUSION: Although bortezomib is well tolerated, it does not have antitumor activity as second-line therapy in UC.

Authors
Rosenberg, JE; Halabi, S; Sanford, BL; Himelstein, AL; Atkins, JN; Hohl, RJ; Millard, F; Bajorin, DF; Small, EJ; Cancer and Leukemia Group B,
MLA Citation
Rosenberg, JE, Halabi, S, Sanford, BL, Himelstein, AL, Atkins, JN, Hohl, RJ, Millard, F, Bajorin, DF, Small, EJ, and Cancer and Leukemia Group B, . "Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207." Ann Oncol 19.5 (May 2008): 946-950.
PMID
18272914
Source
pubmed
Published In
Annals of Oncology
Volume
19
Issue
5
Publish Date
2008
Start Page
946
End Page
950
DOI
10.1093/annonc/mdm600

Statistical considerations for the design and analysis of Phase III clinical trials in prostate cancer.

This article reviews the basic principles involved in the design, conduct, and analysis of Phase III treatment trials in prostate cancer. It begins with a brief review of Phase III trials, and subsequently describes the process of hypothesis testing and the types of errors involved in the process of statistical inference. Next, it presents a general discussion of design considerations, including choice of endpoints, patient selection and eligibility criteria, randomization and stratification, methods to determine the required number patients, standard procedures to monitor a study, and finally how to analyze the results from randomized clinical trials.

Authors
Halabi, S
MLA Citation
Halabi, S. "Statistical considerations for the design and analysis of Phase III clinical trials in prostate cancer." Urol Oncol 26.3 (May 2008): 300-307. (Review)
PMID
18452825
Source
pubmed
Published In
Urologic Oncology: Seminars and Original Investigations
Volume
26
Issue
3
Publish Date
2008
Start Page
300
End Page
307
DOI
10.1016/j.urolonc.2006.11.007

p53 protein expression status and recurrence in men treated with radiation and androgen suppression therapy for higher-risk prostate cancer: a prospective phase II Cancer and Leukemia Group B Study (CALGB 9682).

OBJECTIVES: It has been hypothesized that abnormal p53 protein expression is associated with a worse prognosis after radiation (RT) and androgen suppression therapy (AST). This hypothesis was prospectively tested. METHODS: Between May 1997 and April 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered on a study evaluating whether the endorectal magnetic resonance imaging (eMRI)-defined change in tumor volume (TV) during neoadjuvant (n) AST was associated with prostate-specific antigen (PSA) outcome. Of these, 141 had sufficient tissue to perform immunohistochemical detection of the p53 protein expression status and 113 had complete eMRI information. Multivariable Cox regression analysis was used to assess whether p53 protein expression status predicted time to PSA failure adjusting for known prognostic factors. RESULTS: After a median follow-up of 6.9 years and adjusting for PSA level, Gleason score, clinical stage, and eMRI-defined TV change during nAST, men with abnormal compared with normal p53 expression were at increased risk of PSA failure (hazard ratio [HR]: 2.8; 95% confidence interval [CI]: 1.3-5.9; P = 0.008 for the 141; HR: 2.4; 95% CI: 1.1-5.4; P = 0.03 for the 113). Adjusted estimates of PSA failure were significantly higher (P = 0.03) in men with abnormal compared with normal p53 expression. At 5 years, these respective estimates were 33% and 18%. CONCLUSIONS: Maximizing local control and randomized trials evaluating the impact on survival of adding novel agents to maximal local therapy are warranted in men whose prostate cancer demonstrates abnormal p53 expression.

Authors
D'Amico, AV; Halabi, S; Vollmer, R; Loffredo, M; McMahon, E; Sanford, B; Archer, L; Vogelzang, NJ; Small, EJ; Kantoff, PW; Cancer and Leukemia Group B,
MLA Citation
D'Amico, AV, Halabi, S, Vollmer, R, Loffredo, M, McMahon, E, Sanford, B, Archer, L, Vogelzang, NJ, Small, EJ, Kantoff, PW, and Cancer and Leukemia Group B, . "p53 protein expression status and recurrence in men treated with radiation and androgen suppression therapy for higher-risk prostate cancer: a prospective phase II Cancer and Leukemia Group B Study (CALGB 9682)." Urology 71.5 (May 2008): 933-937.
PMID
18291508
Source
pubmed
Published In
Urology
Volume
71
Issue
5
Publish Date
2008
Start Page
933
End Page
937
DOI
10.1016/j.urology.2007.11.005

Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group.

PURPOSE: To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. METHODS: A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. RESULTS: The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or "no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. CONCLUSION: PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit.

Authors
Scher, HI; Halabi, S; Tannock, I; Morris, M; Sternberg, CN; Carducci, MA; Eisenberger, MA; Higano, C; Bubley, GJ; Dreicer, R; Petrylak, D; Kantoff, P; Basch, E; Kelly, WK; Figg, WD; Small, EJ; Beer, TM; Wilding, G; Martin, A; Hussain, M; Prostate Cancer Clinical Trials Working Group,
MLA Citation
Scher, HI, Halabi, S, Tannock, I, Morris, M, Sternberg, CN, Carducci, MA, Eisenberger, MA, Higano, C, Bubley, GJ, Dreicer, R, Petrylak, D, Kantoff, P, Basch, E, Kelly, WK, Figg, WD, Small, EJ, Beer, TM, Wilding, G, Martin, A, Hussain, M, and Prostate Cancer Clinical Trials Working Group, . "Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group." J Clin Oncol 26.7 (March 1, 2008): 1148-1159.
PMID
18309951
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Issue
7
Publish Date
2008
Start Page
1148
End Page
1159
DOI
10.1200/JCO.2007.12.4487

Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup.

BACKGROUND: The objective of this study was to determine whether cyclin E overexpression defines an etiologically distinct subgroup of ovarian cancer. METHODS: We analyzed data from 538 epithelial ovarian cancer cases and 629 controls enrolled in a population-based case-control study. Cyclin E protein overexpression was assessed using immunohistochemistry. Case-control and case-case comparisons were done to evaluate the relationship between cyclin E overexpression and epidemiologic risk factors. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. RESULTS: Case-control comparisons showed ovarian cancers with and without cyclin E overexpression have different associations with several epidemiologic risk factors. A dose-response relationship was observed between lifetime ovulatory cycles (LOC) and ovarian cancer that overexpressed cyclin E [OR, 1.8; 95% CI, 1.1-3.0 for moderately high LOC (265-390 cycles) and OR, 2.7; 95% CI, 1.6-4.5 for high LOC (>390 cycles) compared with low LOC (<265 cycles)], but no relationship was seen with cancers that lacked overexpression. The most important components of the LOC variable contributing to the differences in the association with the cyclin E subgroups of ovarian cancer were months of oral contraceptive use and months pregnant. CONCLUSIONS: Cyclin E overexpression is associated with a high number of LOC, largely influenced by oral contraceptive use and pregnancy. This suggests that cyclin E overexpression is a molecular signature characteristic of ovarian cancer cases that may arise via a pathway that involves ovulation-induced alterations.

Authors
Schildkraut, JM; Moorman, PG; Bland, AE; Halabi, S; Calingaert, B; Whitaker, R; Lee, PS; Elkins-Williams, T; Bentley, RC; Marks, JR; Berchuck, A
MLA Citation
Schildkraut, JM, Moorman, PG, Bland, AE, Halabi, S, Calingaert, B, Whitaker, R, Lee, PS, Elkins-Williams, T, Bentley, RC, Marks, JR, and Berchuck, A. "Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup." Cancer Epidemiol Biomarkers Prev 17.3 (March 2008): 585-593.
PMID
18349276
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
17
Issue
3
Publish Date
2008
Start Page
585
End Page
593
DOI
10.1158/1055-9965.EPI-07-0596

Second-line chemotherapy for advanced hormone-refractory prostate cancer.

Prostate cancer is the most common cancer occurring among men in the United States. In spite of the disease's favorable prognosis, approximately 30,000 U.S. men develop incurable metastatic disease each year, making prostate cancer the second-leading cause of cancer-related deaths among men in the United States. Although hormone-based therapies generally result in rapid responses, virtually all patients ultimately develop androgen-independent progressive disease. It is among these men with hormone-refractory prostate cancer (HRPC) that the role of chemotherapy continues to be investigated. To date, three drugs (estramustine, mitoxantrone, and docetaxel) have been approved by the US Food and Drug Administration (FDA) for first-line chemotherapy in HRPC, with other agents and combinations now under evaluation in ongoing clinical trials. Patients whose tumors progress through first-line chemotherapy have limited treatment options available to them and less than half of all men with HRPC will receive any second-line chemotherapy. To date, only one phase III randomized clinical trial has been completed in this setting and no therapies are FDA-approved. We review here the entirety of phase II and III data evaluating chemotherapy agents in second-line HRPC.

Authors
Garmey, EG; Sartor, O; Halabi, S; Vogelzang, NJ
MLA Citation
Garmey, EG, Sartor, O, Halabi, S, and Vogelzang, NJ. "Second-line chemotherapy for advanced hormone-refractory prostate cancer." Clin Adv Hematol Oncol 6.2 (February 2008): 118-132. (Review)
PMID
18347563
Source
pubmed
Published In
Clinical advances in hematology & oncology : H&O
Volume
6
Issue
2
Publish Date
2008
Start Page
118
End Page
132

Circulating levels of inflammatory cytokines and risk of colorectal adenomas.

The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-alpha in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-alpha were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between known risk factors for colorectal neoplasia and circulating levels of inflammatory cytokines and associations between inflammatory cytokines and colorectal adenomas. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines, including older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-alpha and, to a lesser degree, with CRP. For IL-6, adjusted odds ratios (OR) for colorectal adenomas were 1.79 [95% confidence interval (CI), 1.19-2.69] for the second highest plasma level and 1.85 (95% CI, 1.24-2.75) for the highest level compared with the reference level. A similar association was found with TNF-alpha, with adjusted ORs of 1.56 (95% CI, 1.03-2.36) and 1.66 (95% CI, 1.10-2.52), respectively. Our findings indicate that systemic inflammation might be involved in the early development of colorectal neoplasia.

Authors
Kim, S; Keku, TO; Martin, C; Galanko, J; Woosley, JT; Schroeder, JC; Satia, JA; Halabi, S; Sandler, RS
MLA Citation
Kim, S, Keku, TO, Martin, C, Galanko, J, Woosley, JT, Schroeder, JC, Satia, JA, Halabi, S, and Sandler, RS. "Circulating levels of inflammatory cytokines and risk of colorectal adenomas." Cancer Res 68.1 (January 1, 2008): 323-328.
PMID
18172326
Source
pubmed
Published In
Cancer Research
Volume
68
Issue
1
Publish Date
2008
Start Page
323
End Page
328
DOI
10.1158/0008-5472.CAN-07-2924

A phase II trial of cisplatin, fixed dose-rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102.

OBJECTIVE: To conduct a phase II trial to determine the efficacy of cisplatin, a fixed dose-rate infusion of gemcitabine and gefitinib (an orally active epidermal growth factor receptor tyrosine kinase inhibitor) in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: Eligible patients had previously untreated measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2 and creatinine clearance of >50 mL/min. The treatment regimen consisted of cisplatin 70 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) on day 1 and 8, administered at a fixed dose rate of 10 mg/m(2)/min, given every 3 weeks concurrent with gefitinib 500 mg/day orally for a maximum of six cycles. Maintenance gefitinib 500 mg/day was continued for responding or stable disease. RESULTS: In all, 27 patients were accrued before the study was halted because the dose-limiting toxicity (DLT) exceeded pre-established stopping rules. The DLT events were two grade 5 (one infection, one cardiovascular accident) and three with grade 4 non-haematological toxicity. In 25 evaluable patients there were nine objective responses, for an overall response rate of 36% (95% confidence interval, CI, 18-57%). The median (95% CI) survival time was 11.1 (5.2-35.3) months. CONCLUSION: The combination of cisplatin, fixed dose-rate gemcitabine and gefitinib is active in advanced TCC, although the relative contribution of gefitinib cannot be determined. However, this regimen was associated with excessive toxicity.

Authors
Philips, GK; Halabi, S; Sanford, BL; Bajorin, D; Small, EJ; Cancer and Leukaemia Group B,
MLA Citation
Philips, GK, Halabi, S, Sanford, BL, Bajorin, D, Small, EJ, and Cancer and Leukaemia Group B, . "A phase II trial of cisplatin, fixed dose-rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102." BJU Int 101.1 (January 2008): 20-25.
PMID
17922873
Source
pubmed
Published In
Bju International
Volume
101
Issue
1
Publish Date
2008
Start Page
20
End Page
25
DOI
10.1111/j.1464-410X.2007.07226.x

Sample size selection in clinical trials when population means are subject to a partial order: One-sided ordered alternatives

The statistical methodology under order restriction is very mathematical and complex. Thus, we provide a brief methodological background of order-restricted likelihood ratio tests for the normal theoretical case for the basic understanding of its applications, and relegate more technical details to the appendices. For data analysis, algorithms for computing the order-restricted estimates and computation of p-values are described. A two-step procedure is presented for obtaining the sample size in clinical trials when the minimum power, say 0.80 or 0.90 is specified, and the normal means satisfy an order restriction. Using this approach will result in reduction of 14-24% in the sample size required when one-sided ordered alternatives are used, as illustrated by several examples.

Authors
Singh, B; Halabi, S; Schell, MJ
MLA Citation
Singh, B, Halabi, S, and Schell, MJ. "Sample size selection in clinical trials when population means are subject to a partial order: One-sided ordered alternatives." Journal of Applied Statistics 35.5 (2008): 583-600.
Source
scival
Published In
Journal of Applied Statistics
Volume
35
Issue
5
Publish Date
2008
Start Page
583
End Page
600
DOI
10.1080/02664760801924780

In reply

Authors
Halabi, S; Vogelzang, NJ; Kornblith, AB; Ou, S-S; Kantoff, PW; Dawson, NA; Small, EJ
MLA Citation
Halabi, S, Vogelzang, NJ, Kornblith, AB, Ou, S-S, Kantoff, PW, Dawson, NA, and Small, EJ. "In reply." Journal of Clinical Oncology 26.25 (2008): 4216-4217.
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
25
Publish Date
2008
Start Page
4216
End Page
4217
DOI
10.1200/JCO.2008.18.5496

In reply

Authors
Scher, HI; Halabi, S; Tannock, IF; Morris, M; Sternberg, CN; Carducci, MA; Eisenberger, MA; Higano, C; Bubley, GJ; Dreicer, R; Petrylak, DP; Kantoff, P; Basch, E; Kelly, WK; Figg, WD; Small, EJ; Beer, TM; Wilding, G; Martin, A; Hussain, M
MLA Citation
Scher, HI, Halabi, S, Tannock, IF, Morris, M, Sternberg, CN, Carducci, MA, Eisenberger, MA, Higano, C, Bubley, GJ, Dreicer, R, Petrylak, DP, Kantoff, P, Basch, E, Kelly, WK, Figg, WD, Small, EJ, Beer, TM, Wilding, G, Martin, A, and Hussain, M. "In reply." Journal of Clinical Oncology 26.21 (2008): 3648-3649.
Source
scival
Published In
Journal of Clinical Oncology
Volume
26
Issue
21
Publish Date
2008
Start Page
3648
End Page
3649
DOI
10.1200/JCO.2008.17.2494

Flexible Frames and Control Sampling in Case-Control Studies

Authors
Potthoff, RF; Halabi, S; Schildkraut, JM; Newman, B
MLA Citation
Potthoff, RF, Halabi, S, Schildkraut, JM, and Newman, B. "Flexible Frames and Control Sampling in Case-Control Studies." The American Statistician 62.4 (2008): 307-313.
Source
repec
Published In
The American Statistician
Volume
62
Issue
4
Publish Date
2008
Start Page
307
End Page
313

Inverse correlation between body mass index and clinical outcomes in men with advanced castration-recurrent prostate cancer.

BACKGROUND: Obesity has a variety of adverse health outcomes, but to the authors' knowledge, the effect of obesity on outcome in patients with advanced prostate cancer is not known. For this reason, the correlation between an elevated body mass index (BMI) and clinical outcomes in patients with metastatic, castration-recurrent prostate cancer (CRPC) was evaluated. METHODS: A total of 1226 men with CRPC who were enrolled in 9 prospective clinical trials conducted by the Cancer and Leukemia Group B (CALGB) for the treatment of metastatic disease were considered. Eligible patients had progressive prostate cancer during androgen deprivation therapy (with documented castrate levels of testosterone); an Eastern Cooperative Oncology Group performance status of 0 to 2; and adequate hematologic, renal, and hepatic function. Patients were classified based on BMI as normal (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and mildly to severely obese (> or =30 kg/m(2)). RESULTS: Approximately 24% of the patients had a normal BMI, 43% were overweight, and 33% were mildly to severely obese. On multivariable analysis, BMI was found to be a statistically significant predictor of overall survival and prostate cancer-specific mortality. Compared with men with normal BMIs, the hazard ratios for death for overweight men and mildly to severely obese men were 0.80 (95% confidence interval [95% CI], 0.68-0.93; P = .001) and 0.80 (95% CI, 0.68-0.94; P = .010), respectively. CONCLUSIONS: In patients with metastatic CRPC, obesity (as defined by an elevated BMI) appears to have a protective effect against overall mortality and prostate cancer-specific mortality. Alternatively, a higher BMI may reflect different cancer biology (ie, the lack of cachexia-producing substances). Further studies to gain a more comprehensive understanding of the mechanisms behind these clinical observations are needed.

Authors
Halabi, S; Ou, S-S; Vogelzang, NJ; Small, EJ
MLA Citation
Halabi, S, Ou, S-S, Vogelzang, NJ, and Small, EJ. "Inverse correlation between body mass index and clinical outcomes in men with advanced castration-recurrent prostate cancer." Cancer 110.7 (October 1, 2007): 1478-1484.
PMID
17665494
Source
pubmed
Published In
Cancer
Volume
110
Issue
7
Publish Date
2007
Start Page
1478
End Page
1484
DOI
10.1002/cncr.22932

American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma.

PURPOSE: To update the recommendations for the use of bisphosphonates in the prevention and treatment of bone disease in multiple myeloma. The Update Committee expanded the guideline to include a discussion of osteonecrosis of the jaw (ONJ). METHODS: For the 2007 update, an Update Committee composed of members from the full panel completed a review and analysis of data published since 2002. Searches of Medline and the Cochrane Collaboration Library databases were performed. RECOMMENDATIONS: For multiple myeloma patients who have, on plain radiograph(s) or imaging studies, lytic destruction of bone or spine compression fracture from osteopenia, intravenous pamidronate 90 mg delivered over at least 2 hours or zoledronic acid 4 mg delivered over at least 15 minutes every 3 to 4 weeks is recommended. Clodronate is an alternative bisphosphonate approved worldwide, except in the United States, for oral or intravenous administration. New dosing guidelines for patients with pre-existing renal impairment were added to the zoledronic acid package insert. Although no similar dosing guidelines are available for pamidronate, the Update Committee recommends that clinicians consider reducing the initial pamidronate dose in patients with pre-existing renal impairment. Zoledronic acid has not been studied in patients with severe renal impairment and is not recommended in this setting. The Update Committee suggests that bisphosphonate treatment continue for a period of 2 years. At 2 years, physicians should seriously consider discontinuing bisphosphonates in patients with responsive or stable disease, but further use is at the discretion of the treating physician. The Update Committee also discusses measures regarding ONJ.

Authors
Kyle, RA; Yee, GC; Somerfield, MR; Flynn, PJ; Halabi, S; Jagannath, S; Orlowski, RZ; Roodman, DG; Twilde, P; Anderson, K; American Society of Clinical Oncology,
MLA Citation
Kyle, RA, Yee, GC, Somerfield, MR, Flynn, PJ, Halabi, S, Jagannath, S, Orlowski, RZ, Roodman, DG, Twilde, P, Anderson, K, and American Society of Clinical Oncology, . "American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma." J Clin Oncol 25.17 (June 10, 2007): 2464-2472.
PMID
17515569
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
17
Publish Date
2007
Start Page
2464
End Page
2472
DOI
10.1200/JCO.2007.12.1269

Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer and leukemia group B study.

PURPOSE: Adrenal androgens activate the androgen receptor and stimulate prostate cancer growth. Ketoconazole is used as an inhibitor of adrenal androgen synthesis in men with androgen-independent prostate cancer. This study analyzes the relationship between pretreatment androgen levels and outcome following ketoconazole treatment. EXPERIMENTAL DESIGN: Baseline levels of three adrenal androgens (androstenedione, dehydroepiandrostenedione, and dehydroepiandrostenedione-sulfate) and testosterone were measured. Regression models (logistic and proportional hazard) were used to assess the prognostic significance of these levels in predicting overall survival and prostate-specific antigen (PSA) response defined by Consensus Criteria. RESULTS: In 103 patients with available levels, PSA response rate was 28% and median response duration was 4.8 months. The median baseline androstenedione level was 0.64 ng/mL and was 0.88 ng/mL versus 0.53 ng/mL for those with and without a PSA response, respectively (P = 0.034). In univariate analysis, elevation of baseline androstenedione levels was predictive of PSA response [odds ratio, 2.26; 95% confidence interval (95% CI), 1.03-4.96; P = 0.043]. In multivariate analysis, both the uppermost and the middle tertile of baseline androstenedione level were associated with an improved overall survival compared with those in the lower tertile (hazard ratio, 0.59; 95% CI, 0.36-0.98; P = 0.40; hazard ratio, 0.53; 95% CI, 0.32-0.90; P = 0.018, respectively). A linear correlation was observed among all androgen levels. CONCLUSIONS: Higher androstenedione levels predict likelihood of response to ketoconazole and improved survival compared with patients with lower levels. These data suggest that therapy with ketoconazole is less effective in patients with low levels of androgen at baseline.

Authors
Ryan, CJ; Halabi, S; Ou, S-S; Vogelzang, NJ; Kantoff, P; Small, EJ
MLA Citation
Ryan, CJ, Halabi, S, Ou, S-S, Vogelzang, NJ, Kantoff, P, and Small, EJ. "Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer and leukemia group B study." Clin Cancer Res 13.7 (April 1, 2007): 2030-2037.
PMID
17404083
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
7
Publish Date
2007
Start Page
2030
End Page
2037
DOI
10.1158/1078-0432.CCR-06-2344

Trinucleotide repeat polymorphisms in the androgen receptor gene and risk of ovarian cancer.

INTRODUCTION: Androgens may play a role in the development of ovarian cancers. Two trinucleotide repeat polymorphisms have been described in exon 1 of the androgen receptor (AR) gene that may affect its function. Previous studies of ovarian cancer and AR repeat polymorphisms have been inconsistent. METHODS: We analyzed CAG and GGC repeat length polymorphisms in the AR gene using data from a population-based case-control study of ovarian cancer that included 594 cases and 681 controls. Repeat lengths were determined by fluorescent DNA fragment analysis using ABI GeneScan software. Change point models were used to determine appropriate repeat length cutoff points by race (African American versus Caucasian) for both the shorter and longer CAG and GGC repeats. RESULTS: No relationship was observed between CAG repeat length and ovarian cancer among Caucasians. Among African Americans, having a short repeat length on either allele was associated with a 2-fold increase in ovarian cancer risk (age-adjusted odds ratio, 2.2; 95% confidence interval, 1.1-4.1). Having short CAG repeat lengths for both alleles was associated with a 5-fold increased risk for developing ovarian cancer (age-adjusted odds ratio, 5.4; 95% confidence interval, 1.4-1.7). No relationship with the GGC repeat length polymorphisms was observed. CONCLUSION: These results suggest that having a short CAG repeat length in AR increases ovarian cancer risk in African Americans. The failure to observe this relationship in Caucasians may be due to the rarity of such short CAG alleles in this population or could reflect racial differences in disease etiology.

Authors
Schildkraut, JM; Murphy, SK; Palmieri, RT; Iversen, E; Moorman, PG; Huang, Z; Halabi, S; Calingaert, B; Gusberg, A; Marks, JR; Berchuck, A
MLA Citation
Schildkraut, JM, Murphy, SK, Palmieri, RT, Iversen, E, Moorman, PG, Huang, Z, Halabi, S, Calingaert, B, Gusberg, A, Marks, JR, and Berchuck, A. "Trinucleotide repeat polymorphisms in the androgen receptor gene and risk of ovarian cancer." Cancer Epidemiol Biomarkers Prev 16.3 (March 2007): 473-480.
PMID
17372242
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
16
Issue
3
Publish Date
2007
Start Page
473
End Page
480
DOI
10.1158/1055-9965.EPI-06-0868

The impact of prior radical prostatectomy in men with metastatic castration recurrent prostate cancer: a pooled analysis of 9 Cancer and Leukemia Group B Trials.

PURPOSE: A prior report suggested that radical prostatectomy may confer a survival advantage to patients with metastatic castration recurrent prostate cancer. Therefore, a pooled analysis of 9 trials performed by Cancer and Leukemia Group B was done to determine if men with metastatic castration recurrent prostate cancer who underwent prior prostatectomy had improved clinical outcomes, such as overall, prostate specific, progression-free and PSA progression-free survival, than men who did not undergo prior prostatectomy. MATERIALS AND METHODS: Data from 9 multi-institutional trials performed by Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer during androgen deprivation therapy, Eastern Cooperative Oncology Group performance status 0-2, and adequate hematological, renal and hepatic functions. The proportional hazards model was used to assess the prognostic importance of radical prostatectomy for predicting clinical outcomes. RESULTS: Of 1,238 men 310 (25%) underwent prostatectomy. Median survival was 14.7 (95% CI 12.9-16.7) and 14.5 months (95% CI 13.5-15.7) in men who did and did not undergo prostatectomy, respectively. The HR for death was 1.03 (95% CI 0.90-1.19, p = 0.65) in men with vs without prostatectomy. CONCLUSIONS: Prior prostatectomy in men with metastatic castration recurrent prostate cancer who were subsequently enrolled on clinical trials for cancer treatment had similar survival compared to men who did not undergo prior prostatectomy. These data do not support another report suggesting that prior prostatectomy confers a subsequent survival advantage in men with castration recurrent prostate cancer.

Authors
Halabi, S; Vogelzang, NJ; Ou, S-S; Small, EJ
MLA Citation
Halabi, S, Vogelzang, NJ, Ou, S-S, and Small, EJ. "The impact of prior radical prostatectomy in men with metastatic castration recurrent prostate cancer: a pooled analysis of 9 Cancer and Leukemia Group B Trials." J Urol 177.2 (February 2007): 531-534.
PMID
17222627
Source
pubmed
Published In
The Journal of Urology
Volume
177
Issue
2
Publish Date
2007
Start Page
531
End Page
534
DOI
10.1016/j.juro.2006.09.050

ASCO 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma: Guideline summary

Authors
Kyle, RA; Yee, GC; Somerfield, MR; Flynn, PJ; Halabi, S; Jagannath, S; Orlowski, RZ; Roodman, DG; Twilde, P; Anderson, K
MLA Citation
Kyle, RA, Yee, GC, Somerfield, MR, Flynn, PJ, Halabi, S, Jagannath, S, Orlowski, RZ, Roodman, DG, Twilde, P, and Anderson, K. "ASCO 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma: Guideline summary." Journal of Oncology Practice 3.4 (2007): 236--.
Source
scival
Published In
Journal of Oncology Practice
Volume
3
Issue
4
Publish Date
2007
Start Page
236-
DOI
10.1200/JOP.0748502

A phase II study of gemcitabine and capecitabine in metastatic renal cancer: a report of Cancer and Leukemia Group B protocol 90008.

BACKGROUND: The objective of this study was to verify previous reports of activity with gemcitabine plus a fluoropyrimidine in patients with metastatic renal cell cancer in a multiinstitutional setting. METHODS: Eligibility included a Zubrod performance status from 0 to 2, no prior gemcitabine or fluoropyrimidine therapy, and normal organ function. Patients received gemcitabine at a dose of 1000 mg/m2 on Days 1, 8, and 15 and capecitabine at a dose of 830 mg/m2 twice daily on Days 1 through 21 on a 28-day cycle with specified dose reductions for baseline renal insufficiency. The primary endpoint was the response rate, which was assessed every 8 weeks. The statistical plan tested the hypothesis that the response rate was 5% versus an alternative of 15%. RESULTS: Sixty patients were enrolled, and 4 of those patients never started treatment. Of the 56 evaluable patients, 79% of patients underwent prior nephrectomy, 75% of patients received prior systemic therapy, and 75% of patients had clear cell histology. Risk stratification revealed that 34%, 43%, and 16% of patients were in Risk Groups 1, 2, and 3, respectively. Toxicity (graded according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included Grade 3 or 4 neutropenia in 45% of patients, Grade 2 or greater fatigue in 32% of patients, Grade 2 or greater nausea in 29% of patients, Grade 2 or greater hand-foot reaction in 39% of patients, and Grade 2 or greater diarrhea in 22% of patients. Six patients responded (11%; 95% confidence interval, 4-22%), and the overall median survival was 14.5 months. CONCLUSIONS: Gemcitabine plus capecitabine had modest activity in patients with metastatic renal cancer, although the degree of activity and its associated toxicity would not support further evaluation in a Phase III trial of unselected patients. More focused investigations to identify patients most likely to benefit or to enhance activity with additional agents would be reasonable.

Authors
Stadler, WM; Halabi, S; Rini, B; Ernstoff, MS; Davila, E; Picus, J; Barrier, R; Small, EJ; Cancer and Leukemia Group B,
MLA Citation
Stadler, WM, Halabi, S, Rini, B, Ernstoff, MS, Davila, E, Picus, J, Barrier, R, Small, EJ, and Cancer and Leukemia Group B, . "A phase II study of gemcitabine and capecitabine in metastatic renal cancer: a report of Cancer and Leukemia Group B protocol 90008." Cancer 107.6 (September 15, 2006): 1273-1279.
PMID
16909426
Source
pubmed
Published In
Cancer
Volume
107
Issue
6
Publish Date
2006
Start Page
1273
End Page
1279
DOI
10.1002/cncr.22117

Adoptive immunotherapy by allogeneic stem cell transplantation for metastatic renal cell carcinoma: a CALGB intergroup phase II study.

A graft-versus-tumor effect through nonmyeloablative allogeneic stem cell transplantation (N-SCT) in metastatic renal cell carcinoma (RCC) has been reported. An Intergroup phase II trial was undertaken to define further the feasibility, toxicity and efficacy of this approach in a multi-institutional setting, Patients with cytokine-refractory, metastatic RCC were treated with N-SCT. The conditioning regimen was fludarabine 30 mg . m(-2) . d(-1) on day (d) -7 through d -3 and cyclophosphamide 60 mg . kg(-1) . d(-1) on d -4 and d -3. Patients received 2-8 x 10(6) CD34+ cells/kg of granulocyte colony-stimulating factor mobilized stem cells from a 6/6 HLA-matched sibling donor. Immunosuppression after transplantation included tacrolimus and methotrexate. Twenty-two patients were enrolled at 14 institutions. Greater than 90% donor T-cell chimerism was observed in 17 of 19 evaluable patients (89%) by d +120. No objective response was observed. Acute graft-versus-host disease (GVHD) was observed in 11 patients (50%). Chronic GVHD was reported in 5 patients (23%). There was 1 patient death from liver failure secondary to chronic GVHD. Regimen-related mortality was 2 of 22 (9%; liver failure, sepsis). Median survival time was 5.5 months (95% confidence interval, 3.9-12.0 months) and the median time to progression was 3.0 months (95% confidence interval, 2.3-4.2 months). N-SCT for metastatic RCC is feasible in a multi-institutional setting. Adequate donor T-cell engraftment was achieved in most patients before disease progression. A graft-versus-tumor effect was not observed in this study despite acute and chronic GVHD, thus highlighting the need for further understanding of this approach. Allogeneic SCT remains investigational in RCC.

Authors
Rini, BI; Halabi, S; Barrier, R; Margolin, KA; Avigan, D; Logan, T; Stadler, WM; McCarthy, PL; Linker, CA; Small, EJ; Cancer and Leukemia Group B, ; Eastern Cooperative Oncology Group, ; Southwestern Oncology Group,
MLA Citation
Rini, BI, Halabi, S, Barrier, R, Margolin, KA, Avigan, D, Logan, T, Stadler, WM, McCarthy, PL, Linker, CA, Small, EJ, Cancer and Leukemia Group B, , Eastern Cooperative Oncology Group, , and Southwestern Oncology Group, . "Adoptive immunotherapy by allogeneic stem cell transplantation for metastatic renal cell carcinoma: a CALGB intergroup phase II study." Biol Blood Marrow Transplant 12.7 (July 2006): 778-785.
PMID
16785067
Source
pubmed
Published In
Biology of Blood and Marrow Transplantation
Volume
12
Issue
7
Publish Date
2006
Start Page
778
End Page
785
DOI
10.1016/j.bbmt.2006.03.011

Clinical outcomes by age in men with hormone refractory prostate cancer: a pooled analysis of 8 Cancer and Leukemia Group B (CALGB) studies.

PURPOSE: We determined if age is a prognostic factor of clinical outcomes, specifically overall survival, disease-free survival and progression-free survival in men with hormone refractory prostate cancer. MATERIALS AND METHODS: Data from 8 multi-institutional trials performed by Cancer and Leukemia Group B were combined. Eligible patients had progressive adenocarcinoma of the prostate after androgen ablation, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate hematological, renal and hepatic function. The proportional hazards model stratified by study was used to assess the prognostic importance of age for predicting clinical outcomes. RESULTS: Of 1,194 men 132 (11%) were 50 to 60 years old and 120 (10%) were 80 to 89 years old. Median survival was 12.2 months (95% CI 10.6 to 13.8) in men 50 to 59 years old, 15.9 months (95% CI 14.2 to 17.6) in men 60 to 69 years old, 15.6 months (95% CI 13.8 to 16.9) in men 70 to 79 years old and 8.9 months (95% CI 6.6 to 12.1) in men 80 to 89 years old. Compared to 70 to 79-year-old men the HR for death in octogenarians was 1.3 (95% CI 1.0 to 1.6, p = 0.015). Furthermore, the HR for prostate cancer death in octogenarians was 1.3 (95% CI 1.1 to 1.7, p = 0.010) and in 50 to 59-year-old men it was 1.3 (95% CI 1.0 to 1.6, p = 0.042) compared to men 70 to 79 years old. Black men were at lower risk for death than white men (HR 0.77, 95 CI% 0.65 to 0.92, p = 0.004). CONCLUSIONS: Octogenarians and white men are at increased risk for death compared to other men with hormone refractory prostate cancer.

Authors
Halabi, S; Vogelzang, NJ; Ou, S-S; Kelly, WK; Small, EJ
MLA Citation
Halabi, S, Vogelzang, NJ, Ou, S-S, Kelly, WK, and Small, EJ. "Clinical outcomes by age in men with hormone refractory prostate cancer: a pooled analysis of 8 Cancer and Leukemia Group B (CALGB) studies." J Urol 176.1 (July 2006): 81-86.
PMID
16753374
Source
pubmed
Published In
The Journal of Urology
Volume
176
Issue
1
Publish Date
2006
Start Page
81
End Page
86
DOI
10.1016/S0022-5347(06)00566-0

Activities and accomplishments of the cancer and leukemia group B genitourinary committee.

The Cancer and Leukemia Group B Genitourinary (GU) Committee has developed a multidisciplinary approach to treatment of GU cancer and has integrated correlative science research into the major research themes of the GU Committee. In localized prostate cancer, trials have evaluated novel approaches in radiation therapy. For patients with recurrence after local therapy, a trial evaluating local recurrence with salvage prostatectomy and a study of systemic therapy with "peripheral androgen blockade" were undertaken. Major contributions have been made in developing and testing therapeutics for advanced, androgen-independent prostate cancer (ketoconazole, suramin, estramustine/docetaxel, and docetaxel/bevacizumab), and in developing predictive markers and algorithms to assess prognosis in these patients. Contributions in kidney cancer have included the development of novel trial methodology, such as the randomized discontinuation trial design, and the testing of antiangiogenics. In addition to these areas, future work of the committee will include further development of therapy for earlier-stage prostate cancer patients and bladder cancer patients.

Authors
Small, EJ; Halabi, S; Kantoff, P; D'Amico, A; Stadler, W; Kelley, WK; Mohler, J; Bajorin, D; Vogelzang, NJ
MLA Citation
Small, EJ, Halabi, S, Kantoff, P, D'Amico, A, Stadler, W, Kelley, WK, Mohler, J, Bajorin, D, and Vogelzang, NJ. "Activities and accomplishments of the cancer and leukemia group B genitourinary committee." Clin Cancer Res 12.11 Pt 2 (June 1, 2006): 3596s-3600s. (Review)
PMID
16740791
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
11 Pt 2
Publish Date
2006
Start Page
3596s
End Page
3600s
DOI
10.1158/1078-0432.CCR-06-9005

Prognostic significance of plasma scatter factor/hepatocyte growth factor levels in patients with metastatic hormone- refractory prostate cancer: results from cancer and leukemia group B 150005/9480.

BACKGROUND: Scatter factor, also known as hepatocyte growth factor (SF/HGF), is a polypeptide growth factor thought to be important in the growth and spread of prostatic carcinoma. PATIENTS AND METHODS: Scatter factor/HGF levels in pretreatment plasma samples from 171 men with metastatic hormone-refractory prostate cancer enrolled in CALGB 9480 were quantified by solid-phase, enzyme-linked immunosorbent assay. RESULTS: The Cox proportional hazards model was used to assess the prognostic importance of SF/HGF with adjustment for established prognostic factors. Median SF/HGF was 991 pg/mL (range, 212-2733 pg/mL). In a univariate analysis, although plasma SF/HGF levels above versus below the median value did not reach statistical significance (P = 0.0862), the cutoff point of > 935 pg/mL was associated with a significant reduction in overall survival (P = 0.0334). Patients with SF/HGF levels > 935 pg/mL experienced a median survival of 15 months compared with 19 months for men with SF/HGF levels < or = 935 pg/mL. In a multivariate analysis, adjusting for SF/HGF, prostate-specific antigen, lactate dehydrogenase, and performance status, only plasma alkaline phosphatase was significantly associated with overall survival (hazard ratio, 1.7; 95% confidence interval, 1.2-2.5; P = 0.0017). CONCLUSION: Higher plasma levels of SF/HGF in men with hormone-refractory prostate cancer are associated with a decreased patient survival. Currently, SF/HGF levels do not appear to be of value as a contributor to multivariate models for prediction of outcome, but the association with decreased survival suggests that SF/HGF might be a potential target for therapy.

Authors
Humphrey, PA; Halabi, S; Picus, J; Sanford, B; Vogelzang, NJ; Small, EJ; Kantoff, PW
MLA Citation
Humphrey, PA, Halabi, S, Picus, J, Sanford, B, Vogelzang, NJ, Small, EJ, and Kantoff, PW. "Prognostic significance of plasma scatter factor/hepatocyte growth factor levels in patients with metastatic hormone- refractory prostate cancer: results from cancer and leukemia group B 150005/9480." Clin Genitourin Cancer 4.4 (March 2006): 269-274.
PMID
16729910
Source
pubmed
Published In
Clinical genitourinary cancer
Volume
4
Issue
4
Publish Date
2006
Start Page
269
End Page
274
DOI
10.3816/CGC.2006.n.006

Analgesic drug use and risk of ovarian cancer.

BACKGROUND: Previous epidemiologic research suggests that analgesic use may reduce the risk of ovarian cancer, although results are not consistent. METHODS: In a population-based, case-control study, we analyzed data from 586 ovarian cancer cases and 627 matched controls in North Carolina for the relationship between analgesic use and ovarian cancer risk. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for potential confounders. RESULTS: Use of any nonsteroidal antiinflammatory drugs, including aspirin, within 5 years of diagnosis/interview was found to be associated with a reduction in the risk of ovarian cancer (adjusted OR = 0.72; 95% CI = 0.56-0.92). For use of acetaminophen, the OR was 0.78 (95% CI = 0.56-1.08). CONCLUSIONS: These data support an inverse relationship between the use of both nonsteroidal antiinflammatory drugs and acetaminophen and the risk of ovarian cancer.

Authors
Schildkraut, JM; Moorman, PG; Halabi, S; Calingaert, B; Marks, JR; Berchuck, A
MLA Citation
Schildkraut, JM, Moorman, PG, Halabi, S, Calingaert, B, Marks, JR, and Berchuck, A. "Analgesic drug use and risk of ovarian cancer." Epidemiology 17.1 (January 2006): 104-107.
PMID
16357602
Source
pubmed
Published In
Epidemiology
Volume
17
Issue
1
Publish Date
2006
Start Page
104
End Page
107

Activities and accomplishments of the Cancer and Leukemia Group B Genitourinary Committee

The Cancer and Leukemia Group B Genitourinary (GU) Committee has developed a multidisciplinary approach to treatment of GU cancer and has integrated correlative science research into the major research themes of the GU Committee. In localized prostate cancer, trials have evaluated novel approaches in radiation therapy. For patients with recurrence after local therapy, a trial evaluating local recurrence with salvage prostatectomy and a study of systemic therapy with "peripheral androgen blockade" were undertaken. Major contributions have been made in developing and testing therapeutics for advanced, androgen-independent prostate cancer (ketoconazole, suramin, estramustine/docetaxel, and docetaxel/bevacizumab), and in developing predictive markers and algorithms to assess prognosis in these patients. Contributions in kidney cancer have included the development of novel trial methodology, such as the randomized discontinuation trial design, and the testing of antiangiogenics. In addition to these areas, future work of the committee will include further development of therapy for earlier-stage prostate cancer patients and bladder cancer patients. © 2006 American Association for Cancer Research.

Authors
Small, EJ; Halabi, S; Kantoff, P; D'Amico, A; Stadler, W; Kelley, WK; Mohler, J; Bajorin, D; Vogelzang, NJ
MLA Citation
Small, EJ, Halabi, S, Kantoff, P, D'Amico, A, Stadler, W, Kelley, WK, Mohler, J, Bajorin, D, and Vogelzang, NJ. "Activities and accomplishments of the Cancer and Leukemia Group B Genitourinary Committee." Clinical Cancer Research 12.11 II (2006): 3596s-3600s.
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
11 II
Publish Date
2006
Start Page
3596s
End Page
3600s
DOI
10.1158/1078-0432.CCR-06-9005

Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study.

PURPOSE: Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients. MATERIAL AND METHODS: Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow biopsies were obtained from 184 patients who underwent an office-based, unguided bone marrow biopsy of the posterior iliac crest. RESULTS: Forty-seven of the 184 patients (25.5%) had a positive bone marrow biopsy. When considered in a multivariate logistic regression analysis, lower hemoglobin levels, higher alkaline phosphatase, and higher lactate dehydrogenase levels were associated with a higher likelihood of a positive BMBx. The median survival time was 11 months (95% confidence interval, 8.0-14) among patients with a positive BMBx compared with 23 months (95% confidence interval, 19-27) with a negative BMBx. The median time to progression and time to prostate-specific antigen progression-free survival were also significantly decreased among positive BMBx patients. No patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137 patients with a negative BMBx survived beyond 5 years. DISCUSSION: Using common laboratory values, a specific patient cohort can be defined from whom the yield of a nonguided BMBx would be high enough to justify this approach. For studies that require broader entry criteria, a more directed approach with image guidance is recommended.

Authors
Ross, RW; Halabi, S; Ou, S-S; Rajeshkumar, BR; Woda, BA; Vogelzang, NJ; Small, EJ; Taplin, M-E; Kantoff, PW; Cancer and Leukemia Group B,
MLA Citation
Ross, RW, Halabi, S, Ou, S-S, Rajeshkumar, BR, Woda, BA, Vogelzang, NJ, Small, EJ, Taplin, M-E, Kantoff, PW, and Cancer and Leukemia Group B, . "Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer--a Cancer and Leukemia Group B study." Clin Cancer Res 11.22 (November 15, 2005): 8109-8113.
PMID
16299243
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
22
Publish Date
2005
Start Page
8109
End Page
8113
DOI
10.1158/1078-0432.CCR-05-1250

Anthropometric measurements and epithelial ovarian cancer risk in African-American and White women.

Previous studies of anthropometric factors and ovarian cancer risk have been inconsistent and none have evaluated the association among African-American women. Data from a population-based, case-control study of 593 cases and 628 controls were used to evaluate ovarian cancer risk in relation to weight, height, body mass index (BMI) and waist-to-hip ratio (WHR). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed and established risk factors were adjusted for using logistic regression models, stratified by race. Among all races, weight at age 18, WHR, weight and BMI one year prior to interview were associated with elevated ovarian cancer risk. When stratified by race, the association between WHR and ovarian was similar among Whites and among African Americans. However, African-American women in the fourth quartile of height had an elevated risk of ovarian cancer (OR = 3.2; 95% CI = 1.3-7.8), but this risk was not apparent in Whites (OR = 1.0; 95% CI = 0.7-1.4). These findings support the hypothesis that obesity is an important risk factor of ovarian cancer among African-Americans and Whites and also suggest that height may be a risk factor specific to African-Americans.

Authors
Hoyo, C; Berchuck, A; Halabi, S; Bentley, RC; Moorman, P; Calingaert, B; Schildkraut, JM
MLA Citation
Hoyo, C, Berchuck, A, Halabi, S, Bentley, RC, Moorman, P, Calingaert, B, and Schildkraut, JM. "Anthropometric measurements and epithelial ovarian cancer risk in African-American and White women." Cancer Causes Control 16.8 (October 2005): 955-963.
PMID
16132804
Source
pubmed
Published In
Cancer Causes & Control
Volume
16
Issue
8
Publish Date
2005
Start Page
955
End Page
963
DOI
10.1007/s10552-005-3205-y

Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study.

OBJECTIVES: To test the hypothesis that chromogranin A (CgA) levels are prognostic in patients with metastatic hormone-refractory prostate cancer (HRPC). The extent of neuroendocrine differentiation in prostate cancer correlates with aggressive disease and with progression to HRPC. Plasma CgA levels in patients with prostate cancer may reflect the extent of the tumor neuroendocrine phenotype. METHODS: Pretreatment plasma was collected from 390 patients with metastatic HRPC enrolled in the Cancer and Leukemia Group B (CALGB) 9480 trial, a study of three different doses of suramin. Plasma CgA levels were determined in 321 samples in duplicate using a quantitative sandwich immunoassay. The proportional hazards model was used to assess the prognostic significance of CgA in predicting overall survival. RESULTS: The median plasma CgA level was 12 U/L (interquartile range 7.7 to 19.3). In univariate analysis, plasma CgA correlated inversely with survival times, with a survival time of 17 months for low CgA (less than 12 U/L, 95% CI 14 to 19) compared with 11 months for high CgA (95% CI 8 to 14, P = 0.014) and at all exploratory cutpoints, including CgA of 9.5 U/L or less versus greater than 9.5 U/L, with survival of 19 months compared with 12 months (P = 0.0015). In multivariate models (adjusting for performance status, prostate-specific antigen, and lactate dehydrogenase), the plasma CgA levels remained predictive of overall survival. CONCLUSIONS: These results support the hypothesis that serum CgA levels correlate with outcome in patients with HRPC, although the clinical significance needs to be established in confirmatory studies before incorporation of CgA measurements in clinical practice.

Authors
Taplin, M-E; George, DJ; Halabi, S; Sanford, B; Febbo, PG; Hennessy, KT; Mihos, CG; Vogelzang, NJ; Small, EJ; Kantoff, PW
MLA Citation
Taplin, M-E, George, DJ, Halabi, S, Sanford, B, Febbo, PG, Hennessy, KT, Mihos, CG, Vogelzang, NJ, Small, EJ, and Kantoff, PW. "Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study." Urology 66.2 (August 2005): 386-391.
PMID
16098367
Source
pubmed
Published In
Urology
Volume
66
Issue
2
Publish Date
2005
Start Page
386
End Page
391
DOI
10.1016/j.urology.2005.03.040

Menopausal hormones and risk of ovarian cancer.

OBJECTIVE: The objective of this study was to determine if use of menopausal hormones was associated with ovarian cancer and if risk varied by type of hormone used. STUDY DESIGN: Data from a population-based, case-control study of ovarian cancer in North Carolina (364 cases, 370 controls, all postmenopausal) were analyzed to evaluate the relationship between menopausal hormones and ovarian cancer. Logistic regression analyses were used to calculate odds ratios (OR) and 95% CIs associated with various patterns of hormone use. RESULTS: Ovarian cancer cases were more likely than controls to report long-term use (>or=10 years) of unopposed estrogens (OR 2.2; 95% CI 1.2-4.1). No relationship was observed for estrogen always used with progestin. CONCLUSION: Hormone replacement therapy used according to current recommendations should not increase risk of ovarian cancer; however, clinicians should be aware of possible increased risk among women with a long history of estrogen replacement therapy.

Authors
Moorman, PG; Schildkraut, JM; Calingaert, B; Halabi, S; Berchuck, A
MLA Citation
Moorman, PG, Schildkraut, JM, Calingaert, B, Halabi, S, and Berchuck, A. "Menopausal hormones and risk of ovarian cancer." Am J Obstet Gynecol 193.1 (July 2005): 76-82.
PMID
16021062
Source
pubmed
Published In
American Journal of Obstetrics & Gynecology
Volume
193
Issue
1
Publish Date
2005
Start Page
76
End Page
82
DOI
10.1016/j.ajog.2004.11.013

Antidepressant medication use for and risk of ovarian cancer (vol 105, pg 725, 2005)

Authors
Moorman, PG; Berchuck, A; Calingaert, B; Halabi, S; Schildkraut, AM
MLA Citation
Moorman, PG, Berchuck, A, Calingaert, B, Halabi, S, and Schildkraut, AM. "Antidepressant medication use for and risk of ovarian cancer (vol 105, pg 725, 2005)." OBSTETRICS AND GYNECOLOGY 105.6 (June 2005): 1495-1495.
Source
wos-lite
Published In
Obstetrics & Gynecology (Elsevier)
Volume
105
Issue
6
Publish Date
2005
Start Page
1495
End Page
1495

Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk.

OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase susceptibility to various types of cancer including ovarian cancer. METHODS: The TGFbetaR1 polyalanine polymorphism was genotyped in 588 ovarian cancer cases and 614 controls from a population-based case-control study in North Carolina. RESULTS: Significant racial differences in the frequency of the 6A allele were observed between Caucasian (10.7%) and African-American (2.4%) controls (P < 0.001). One or two copies of the 6A allele of the TGFbetaR1 polyalanine polymorphism was carried by 18% of all controls and 19% of cases, and there was no association with ovarian cancer risk (OR = 1.07, 95% CI 0.80-1.44). The odds ratio for 6A homozygotes was 1.81 (95% CI 0.655.06), but these comprised only 0.98% of controls and 1.70% of cases. CONCLUSIONS: The 6A allele of the TGFbetaR1 polyalanine polymorphism does not appear to increase ovarian cancer risk. Larger studies would be needed to exclude the possibility that the small fraction of individuals who are 6A homozygotes have an increased risk of ovarian or other cancers.

Authors
Spillman, MA; Schildkraut, JM; Halabi, S; Moorman, P; Calingaert, B; Bentley, RC; Marks, JR; Murphy, S; Berchuck, A
MLA Citation
Spillman, MA, Schildkraut, JM, Halabi, S, Moorman, P, Calingaert, B, Bentley, RC, Marks, JR, Murphy, S, and Berchuck, A. "Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk." Gynecol Oncol 97.2 (May 2005): 543-549.
PMID
15863158
Source
pubmed
Published In
Gynecologic Oncology
Volume
97
Issue
2
Publish Date
2005
Start Page
543
End Page
549
DOI
10.1016/j.ygyno.2005.01.025

Elevated body mass index predicts for longer overall survival duration in men with metastatic hormone-refractory prostate cancer.

Authors
Halabi, S; Small, EJ; Vogelzang, NJ
MLA Citation
Halabi, S, Small, EJ, and Vogelzang, NJ. "Elevated body mass index predicts for longer overall survival duration in men with metastatic hormone-refractory prostate cancer." J Clin Oncol 23.10 (April 1, 2005): 2434-2435. (Letter)
PMID
15800342
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
10
Publish Date
2005
Start Page
2434
End Page
2435
DOI
10.1200/JCO.2005.05.890

Antidepressant medication use [corrected] and risk of ovarian cancer.

OBJECTIVE: It has been hypothesized that antidepressants may enhance cancer growth. Previous studies of antidepressant use and ovarian cancer have been inconsistent and have been limited in their ability to examine the association with selective serotonin reuptake inhibitors (SSRIs), which are currently the antidepressants most commonly prescribed. The objective of this paper was to evaluate whether women with ovarian cancer were more likely to report past use of antidepressants than control women. METHODS: Antidepressant use was assessed in a population-based, case-control study of ovarian cancer (593 cases, 628 controls). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with antidepressant use overall and by subcategories of antidepressants. RESULTS: Antidepressant use was reported by 18% of cases and 20% of controls. No increased risk was observed for ever use of any type of antidepressant (OR 0.9, 95% CI 0.7-1.2) or for SSRIs (OR 1.0, 95% CI 0.7-1.5). There also was no evidence of increased risk with longer duration of use. Our study had greater than 80% power to detect an OR as small as 1.5. Thus, even a modest increase in risk associated with antidepressant use can be excluded with these data. CONCLUSION: Our study adds to the growing body of evidence suggesting that antidepressants do not have a significant effect on ovarian cancer risk. In particular, the data suggest that SSRIs, which are the most commonly used class of antidepressants, are not associated with an increased risk for ovarian cancer. LEVEL OF EVIDENCE: II-2.

Authors
Moorman, PG; Berchuck, A; Calingaert, B; Halabi, S; Schildkraut, JM
MLA Citation
Moorman, PG, Berchuck, A, Calingaert, B, Halabi, S, and Schildkraut, JM. "Antidepressant medication use [corrected] and risk of ovarian cancer." Obstet Gynecol 105.4 (April 2005): 725-730.
PMID
15802397
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
105
Issue
4
Publish Date
2005
Start Page
725
End Page
730
DOI
10.1097/01.AOG.0000157113.98061.eb

The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480.

UNLABELLED: Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480 (CALGB 9480)]. METHODS: 191 patients entered on CALGB 9480 had pretreatment plasma collected and centrally stored. Using a human IL-6 immunoassay, quantitative levels of IL-6 were measured in duplicate on 300 muL samples. The proportional hazard model was used to assess the prognostic significance of IL-6 in predicting overall survival. RESULTS: Median IL-6 level for the cohort of 191 patients was 4.80 pg/mL. Survival time among patients with IL-6 levels less than or equal to the median was 19 months (95% CI, 17-22) compared with 11 (95% CI, 8-14) months for patients above the median (P = 0.0004). In multivariate analysis, adjusting on performance status, lactate dehydrogenase, and prostate-specific antigen level, the hazard ratio was 1.38 (95% CI, 1.01-1.89; P = 0.043) using the median level as a cut point. Furthermore, a cut point of 13.31 pg/mL revealed robust prognostic significance with a hazard ratio of 2.02 (95% CI, 1.36-2.98; P = 0.0005). CONCLUSIONS: Plasma IL-6 level has prognostic significance in patients with metastatic HRCaP from CALGB 9480. These findings support using IL-6 levels in prognostic models and support the rationale for IL-6-targeted therapy in patients with HRCaP.

Authors
George, DJ; Halabi, S; Shepard, TF; Sanford, B; Vogelzang, NJ; Small, EJ; Kantoff, PW
MLA Citation
George, DJ, Halabi, S, Shepard, TF, Sanford, B, Vogelzang, NJ, Small, EJ, and Kantoff, PW. "The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480." Clin Cancer Res 11.5 (March 1, 2005): 1815-1820.
PMID
15756004
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
5
Publish Date
2005
Start Page
1815
End Page
1820
DOI
10.1158/1078-0432.CCR-04-1560

Erratum: Antidepressant medication use for and risk of ovarian cancer (Obstetrics and Gynecology (2005) 105 (725-730))

Authors
Moorman, PG; Berchuck, A; Calingaert, B; Halabi, S; Schildkraut, M
MLA Citation
Moorman, PG, Berchuck, A, Calingaert, B, Halabi, S, and Schildkraut, M. "Erratum: Antidepressant medication use for and risk of ovarian cancer (Obstetrics and Gynecology (2005) 105 (725-730))." Obstetrics and Gynecology 105.6 (2005): 1495--.
Source
scival
Published In
Obstetrics and Gynecology
Volume
105
Issue
6
Publish Date
2005
Start Page
1495-
DOI
10.1097/01.AOG.0000151956.00804.78

Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.

OBJECTIVE: The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of the A and B isoforms and has been associated with an increased risk of endometrial and breast cancer. In this study, we sought to determine whether this polymorphism affects ovarian cancer risk. METHODS: The +331G/A polymorphism was genotyped in a population-based, case-control study from North Carolina that included 942 Caucasian subjects (438 cases, 504 controls) and in a confirmatory group from Australia (535 cases, 298 controls). Logistic regression analysis was used to calculate age-adjusted odds ratios (OR). RESULTS: There was a suggestion of a protective effect of the +331A allele (AA or GA) against ovarian cancer in the North Carolina study [OR, 0.72; 95% confidence interval (95% CI), 0.47-1.10]. Examination of genotype frequencies by histologic type revealed that this was due to a decreased risk of endometrioid and clear cell cancers (OR, 0.30; 95% CI, 0.09-0.97). Similarly, in the Australian study, there was a nonsignificant decrease in the risk of ovarian cancer among those with the +331A allele (OR, 0.83; 95% CI, 0.51-1.35) that was strongest in the endometrioid/clear cell group (OR, 0.60; 95% CI, 0.24-1.44). In the combined U.S.-Australian data that included 174 endometrioid/clear cell cases (166 invasive, 8 borderline), the +331A allele was significantly associated with protection against this subset of ovarian cancers (OR, 0.46; 95% CI, 0.23-0.92). Preliminary evidence of a protective effect of the +331A allele against endometriosis was also noted in control subjects (OR, 0.19; 95% CI, 0.03-1.38). CONCLUSIONS: These findings suggest that the +331G/A progesterone receptor promoter polymorphism may modify the molecular epidemiologic pathway that encompasses both the development of endometriosis and its subsequent transformation into endometrioid/clear cell ovarian cancer.

Authors
Berchuck, A; Schildkraut, JM; Wenham, RM; Calingaert, B; Ali, S; Henriott, A; Halabi, S; Rodriguez, GC; Gertig, D; Purdie, DM; Kelemen, L; Spurdle, AB; Marks, J; Chenevix-Trench, G
MLA Citation
Berchuck, A, Schildkraut, JM, Wenham, RM, Calingaert, B, Ali, S, Henriott, A, Halabi, S, Rodriguez, GC, Gertig, D, Purdie, DM, Kelemen, L, Spurdle, AB, Marks, J, and Chenevix-Trench, G. "Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers." Cancer Epidemiol Biomarkers Prev 13.12 (December 2004): 2141-2147.
PMID
15598772
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
13
Issue
12
Publish Date
2004
Start Page
2141
End Page
2147

9-Nitrocamptothecin as second line chemotherapy for men with progressive, metastatic, hormone refractory prostate cancer: Results of the CALGB 99901.

BACKGROUND: Institution of early hormone therapy in the PSA era coupled with demonstration of clinical benefit with chemotherapy in hormone refractory prostate cancer (HRPC) and acceptance of PSA decline as a surrogate for response has resulted in introduction of chemotherapy earlier in the natural history of disease. There now exists a need to identify, effective agents for second line chemotherapy. 9-nitrocamptothecin (9-NC) a novel, oral camptothecin analogue was tested as second line chemotherapy for patients with progressive hormone refractory prostate cancer. PATIENTS AND METHODS: Eligible patients had metastatic hormone refractory prostate cancer with performance status (0-1) following progression on at least 1 prior cytotoxic chemotherapy. 9-NC was administered orally at the dose of 1.5 mg/m2/d for 5 days each week for 3 weeks, followed by rest for 1 week. Response was evaluated after 2 cycles according to the guidelines set forth for Phase II trials in HRPC by the PSA working group. RESULTS: Thirty-five patients were recruited to the study within a period of 6 months; 33 were evaluable for analysis. No patients had a >50% decline in PSA levels. Two out of 8 (25%) patients with measurable disease and 5/25 (20%) patients with nonmeasurable disease showed stable disease. The median time to disease and PSA progression was 2 months [95% confidence interval (CI), 0.9-2.8]. The median overall survival was 10 months (95% CI = 5-12). Seven patients are alive after a median follow-up of 23 months. CONCLUSIONS: 9-nitrocamptothecin failed to elicit clinical or PSA responses. Further study in pretreated HRPC patients is not warranted.

Authors
Amin, A; Halabi, S; Gelmann, EP; Stadler, W; Vogelzang, N; Small, E
MLA Citation
Amin, A, Halabi, S, Gelmann, EP, Stadler, W, Vogelzang, N, and Small, E. "9-Nitrocamptothecin as second line chemotherapy for men with progressive, metastatic, hormone refractory prostate cancer: Results of the CALGB 99901." Urol Oncol 22.5 (September 2004): 398-403.
PMID
15464920
Source
pubmed
Published In
Urologic Oncology: Seminars and Original Investigations
Volume
22
Issue
5
Publish Date
2004
Start Page
398
End Page
403
DOI
10.1016/j.urolonc.2004.05.002

Impact of race on survival in men with metastatic hormone-refractory prostate cancer.

OBJECTIVES: To determine whether blacks with hormone-refractory prostate cancer have shorter survival compared with whites with the same disease. METHODS: Data from eight multicenter trials (four Phase II and four randomized Phase III studies) conducted by the Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer after androgen deprivation therapy (with documented castration levels of testosterone), an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic function. The proportional hazards model was used to assess the prognostic importance of race, adjusting for important factors. All statistical tests were two-sided. RESULTS: Of the 1183 patients, 15% were blacks, 45% of patients had a Gleason sum of 8 or greater, and the median age was 71 years. Of the 1183 patients, 35% had measurable disease and 89% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Blacks were younger, had a shorter interval between diagnosis and study entry, and had greater prostate-specific antigen levels, lower hemoglobin levels, and a lower likelihood of prior prostatectomy than whites. The median survival was 15 months (95% confidence interval 12 to 18) for blacks compared with 14 months (95% confidence interval 13 to 15) for whites. In a multivariate analysis, adjusting for age, performance status, presence of visceral disease, hemoglobin, Gleason sum, prostate-specific antigen level, alkaline phosphatase, lactate dehydrogenase, and years since diagnosis, the hazard ratio was 0.85 (95% confidence interval 0.71 to 1.02, P = 0.08) for blacks compared with whites. CONCLUSIONS: No statistically significant difference was found in overall survival between blacks and whites with metastatic hormone-refractory prostate cancer.

Authors
Halabi, S; Small, EJ; Vogelzang, NJ; Barrier, RC; George, SL; Gilligan, TD
MLA Citation
Halabi, S, Small, EJ, Vogelzang, NJ, Barrier, RC, George, SL, and Gilligan, TD. "Impact of race on survival in men with metastatic hormone-refractory prostate cancer." Urology 64.2 (August 2004): 212-217.
PMID
15302462
Source
pubmed
Published In
Urology
Volume
64
Issue
2
Publish Date
2004
Start Page
212
End Page
217
DOI
10.1016/j.urology.2004.04.014

Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia.

BACKGROUND: The authors undertook a multiinstitutional Phase II cooperative group study to examine the potential of oral fish oil fatty acid supplements administered at high doses to slow weight loss and to improve quality of life in patients with malignancy-related cachexia. METHODS: Patients with advanced malignancy and weight loss > or = 2% of body weight in the preceding month took concentrated, high-dose omega-3 fatty acid capsules (7.5 g eicosapentaenoic acid plus docosahexaenoic acid for a 70 kg individual) that were supplied by the National Institutes of Health. RESULTS: Forty-three patients with moderate or severe malnutrition were enrolled. The median time receiving treatment was 1.2 months. For the 36 patients who took at least 1 capsule and did not have edema, there was a weight change ranging from -6.2 kg to +3.5 kg and an overall median weight loss of 0.8 kg. Twenty-four patients had weight stabilization (a gain of < or = 5% or a loss of < 5%), 6 patients gained > 5% of their body weight, and 6 patients lost > or = 5% of their body weight. There was marked variability in the tolerability of the capsules, and many patients had gastrointestinal side effects. There was a correlation between time receiving treatment and weight gain for the 22 patients who were able to tolerate the capsules for at least 1 month. Quality-of-life scores were superior for patients who gained weight. CONCLUSIONS: A majority of patients did not gain weight, and in that sense, the results of the study were unfavorable. However, a small but definite subset of patients had weight stabilization or weight gain. This suggests that omega-3 fatty acids have potential utility at the study doses, which were more than twice the doses used in published Phase III studies.

Authors
Burns, CP; Halabi, S; Clamon, G; Kaplan, E; Hohl, RJ; Atkins, JN; Schwartz, MA; Wagner, BA; Paskett, E
MLA Citation
Burns, CP, Halabi, S, Clamon, G, Kaplan, E, Hohl, RJ, Atkins, JN, Schwartz, MA, Wagner, BA, and Paskett, E. "Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia." Cancer 101.2 (July 15, 2004): 370-378.
PMID
15241836
Source
pubmed
Published In
Cancer
Volume
101
Issue
2
Publish Date
2004
Start Page
370
End Page
378
DOI
10.1002/cncr.20362

Sample size determination for comparing several survival curves with unequal allocations.

Ahnn and Anderson derived sample size formulae for unstratified and stratified designs assuming equal allocation of subjects to three or more treatment groups. We generalize the sample size formulae to allow for unequal allocation. In addition, we define the overall probability of death to be equal to one minus the censored proportion for the stratified design. This definition also leads to a slightly different definition of the non-centrality parameter than that of Ahnn and Anderson for the stratified case. Assuming proportional hazards, sample sizes are determined for a prespecified power, significance level, hazard ratios, allocation of subjects to several treatment groups, and known censored proportion. In the proportional hazards setting, three cases are considered: (1) exponential failures--exponential censoring, (2) exponential failures--uniform censoring, and (3) Weibull failures (assuming same shape parameter for all groups)--uniform censoring. In all three cases of the unstratified case, it is assumed that the censoring distribution is the same for all of the treatment groups. For the stratified log-rank test, it is assumed the same censoring distribution across the treatment groups and the strata. Further, formulae have been developed to provide approximate powers for the test, based upon the first two or first four-moments of the asymptotic distribution. We observe the following two major findings based on the simulations. First, the simulated power of the log-rank test does not depend on the censoring mechanism. Second, for a significance level of 0.05 and power of 0.80, the required sample size n is independent of the censoring pattern. Moreover, there is very close agreement between the exact (asymptotic) and simulated powers when a sequence of alternatives is close to the null hypothesis. Two-moment and four-moment power series approximations also yield powers in close agreement with the exact (asymptotic) power. With unequal allocations, our simulations show that the empirical powers are consistently above the target value of prespecified power of 0.80 when 50 per cent of the patients are allocated to the treatment group with the smallest hazard.

Authors
Halabi, S; Singh, B
MLA Citation
Halabi, S, and Singh, B. "Sample size determination for comparing several survival curves with unequal allocations." Stat Med 23.11 (June 15, 2004): 1793-1815.
PMID
15160409
Source
pubmed
Published In
Statistics in Medicine
Volume
23
Issue
11
Publish Date
2004
Start Page
1793
End Page
1815
DOI
10.1002/sim.1771

Cancer and Leukemia Group B 90206: A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma.

The majority of sporadic clear cell renal cell carcinoma (RCC) is characterized by loss of heterozygosity of the von Hippel-Lindau (VHL) tumor suppressor gene and somatic inactivation of the remaining VHL allele. The resulting VHL gene silencing leads to induction of hypoxia-regulated genes including vascular endothelial growth factor (VEGF). Thus, therapeutic inhibition of VEGF holds promise for treatment of this historically refractory malignancy. An antibody to VEGF (bevacizumab, Avastin) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC. Interferon-alpha (IFN-alpha) is a standard initial cytokine therapy in RCC with a modest response rate and a survival advantage demonstrated in randomized trials. We hypothesized that the addition of anti-VEGF therapy to IFN-alpha would prolong survival in untreated metastatic RCC patients. A Phase III trial is now being conducted randomizing untreated, metastatic clear cell RCC patients to IFN-alpha alone or IFN-alpha plus Avastin.

Authors
Rini, BI; Halabi, S; Taylor, J; Small, EJ; Schilsky, RL; Cancer and Leukemia Group B,
MLA Citation
Rini, BI, Halabi, S, Taylor, J, Small, EJ, Schilsky, RL, and Cancer and Leukemia Group B, . "Cancer and Leukemia Group B 90206: A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma." Clin Cancer Res 10.8 (April 15, 2004): 2584-2586.
PMID
15102658
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
10
Issue
8
Publish Date
2004
Start Page
2584
End Page
2586

Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583).

PURPOSE: Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of > or =50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy. PATIENTS AND METHODS: AiPCa patients were randomized to undergo AAWD alone (n=132), or together with K (400 mg orally [p.o.] tid) and hydrocortisone (30 mg p.o. each morning, 10 mg p.o. each evening; n=128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K. RESULTS: Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P=.0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P=.02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression. CONCLUSION: K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.

Authors
Small, EJ; Halabi, S; Dawson, NA; Stadler, WM; Rini, BI; Picus, J; Gable, P; Torti, FM; Kaplan, E; Vogelzang, NJ
MLA Citation
Small, EJ, Halabi, S, Dawson, NA, Stadler, WM, Rini, BI, Picus, J, Gable, P, Torti, FM, Kaplan, E, and Vogelzang, NJ. "Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583)." J Clin Oncol 22.6 (March 15, 2004): 1025-1033.
PMID
15020604
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
6
Publish Date
2004
Start Page
1025
End Page
1033
DOI
10.1200/JCO.2004.06.037

Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). RESULTS: HYPOTHESIS: A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. PATIENT POPULATION: The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. INTERVENTION: Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. OUTCOMES: An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. TRIAL DESIGN: The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative. CONCLUSION: Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

Authors
Scher, HI; Eisenberger, M; D'Amico, AV; Halabi, S; Small, EJ; Morris, M; Kattan, MW; Roach, M; Kantoff, P; Pienta, KJ; Carducci, MA; Agus, D; Slovin, SF; Heller, G; Kelly, WK; Lange, PH; Petrylak, D; Berg, W; Higano, C; Wilding, G; Moul, JW; Partin, AN; Logothetis, C; Soule, HR
MLA Citation
Scher, HI, Eisenberger, M, D'Amico, AV, Halabi, S, Small, EJ, Morris, M, Kattan, MW, Roach, M, Kantoff, P, Pienta, KJ, Carducci, MA, Agus, D, Slovin, SF, Heller, G, Kelly, WK, Lange, PH, Petrylak, D, Berg, W, Higano, C, Wilding, G, Moul, JW, Partin, AN, Logothetis, C, and Soule, HR. "Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group." J Clin Oncol 22.3 (February 1, 2004): 537-556.
PMID
14752077
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
3
Publish Date
2004
Start Page
537
End Page
556
DOI
10.1200/JCO.2004.07.099

Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia: A cancer and leukemia group B study

BACKGROUND. The authors undertook a multiinstitutional Phase II cooperative group study to examine the potential of oral fish oil fatty acid supplements administered at high doses to slow weight loss and to improve quality of life in patients with malignancy-related cachexia. METHODS. Patients with advanced malignancy and weight loss ≥ 2% of body weight in the preceding month took concentrated, high-dose omega-3 fatty acid capsules (7.5 g eicosapentaenoic acid plus docosahexaenoic acid for a 70 kg individual) that were supplied by the National Institutes of Health. RESULTS. Forty-three patients with moderate or severe malnutrition were enrolled. The median time receiving treatment was 1.2 months. For the 36 patients who took at least 1 capsule and did not have edema, there was a weight change ranging from -6.2 kg to +3.5 kg and an overall median weight loss of 0.8 kg. Twenty-four patients had weight stabilization (a gain of ≤ 5% or a loss of < 5%), 6 patients gained > 5% of their body weight, and 6 patients lost ≥ 5% of their body weight. There was marked variability in the tolerability of the capsules, and many patients had gastrointestinal side effects. There was a correlation between time receiving treatment and weight gain for the 22 patients who were able to tolerate the capsules for at least 1 month. Quality-of-life scores were superior for patients who gained weight. CONCLUSIONS. A majority of patients did not gain weight, and in that sense, the results of the study were unfavorable. However, a small but definite subset of patients had weight stabilization or weight gain. This suggests that omega-3 fatty acids have potential utility at the study doses, which were more than twice the doses used in published Phase III studies. © 2004 American Cancer Society.

Authors
Burns, CP; Halabi, S; Clamon, G; Kaplan, E; Hohl, RJ; Atkins, JN; Schwartz, MA; Wagner, BA; Paskett, E
MLA Citation
Burns, CP, Halabi, S, Clamon, G, Kaplan, E, Hohl, RJ, Atkins, JN, Schwartz, MA, Wagner, BA, and Paskett, E. "Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia: A cancer and leukemia group B study." Cancer 101.2 (2004): 370-378.
Source
scival
Published In
Cancer
Volume
101
Issue
2
Publish Date
2004
Start Page
370
End Page
378
DOI
10.1002/cncr.20362

A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor support in patients with hormone-refractory prostate carcinoma: Cancer and Leukemia Group B 99813.

BACKGROUND: The authors determined the safety and efficacy of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor (G-CSF) support in patients with hormone-refractory prostate carcinoma. METHODS: In the current multicenter, cooperative group study, patients with advanced prostate carcinoma whose disease progressed despite androgen deprivation therapy were treated with a combination of oral estramustine(240 mg three times per day for 5 days), 70 mg/m2 of docetaxel, and carboplatin at a dose of (area under the curve) 5. G-CSF was used to minimize the neutropenia associated with this regimen. Each cycle was repeated every 21 days. RESULTS: Forty patients were treated with a median of 7 cycles of therapy. Of the 34 evaluable patients with elevated pretreatment prostate-specific antigen (PSA) levels, 23 (68%) had a > or = 50% decline in PSA and 20 (59%) had a > or = 75% decline. Twenty-one patients had measurable disease, with 1 complete response (5%) and 10 partial responses (47%), for an overall measurable response rate of 52% (95% confidence interval [95% CI], 30-74%). The most common Grade 3 or Grade 4 toxicities (according to the National Cancer Institute Common Toxicity Criteria) included neutropenia in 23% of patients, thrombocytopenia in 13%, and fatigue in 13%. Febrile neutropenia occurred in 1 patient (3%). The overall median time to disease progression was 8.1 months (95% CI, 6-10 months) and the overall survival period was 19 months (95% CI, 13-26 months). CONCLUSIONS: The combination of estramustine, docetaxel, and carboplatin with G-CSF support was found to have significant clinical activity with an acceptable toxicity profile in patients with progressive hormone-refractory prostate carcinoma.

Authors
Oh, WK; Halabi, S; Kelly, WK; Werner, C; Godley, PA; Vogelzang, NJ; Small, EJ; Cancer and Leukemia Group B 99813,
MLA Citation
Oh, WK, Halabi, S, Kelly, WK, Werner, C, Godley, PA, Vogelzang, NJ, Small, EJ, and Cancer and Leukemia Group B 99813, . "A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor support in patients with hormone-refractory prostate carcinoma: Cancer and Leukemia Group B 99813." Cancer 98.12 (December 15, 2003): 2592-2598.
PMID
14669278
Source
pubmed
Published In
Cancer
Volume
98
Issue
12
Publish Date
2003
Start Page
2592
End Page
2598
DOI
10.1002/cncr.11829

Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663.

PURPOSE: The mechanisms responsible for prostate cancer androgen independence are diverse. Mutations of the androgen receptor (AR) gene that broaden ligand specificity have been implicated. Bone marrow specimens containing prostate tumor were obtained from men undergoing antiandrogen withdrawal for AR sequence analysis and clinical correlation. MATERIALS AND METHODS: Eligible men enrolled on a trial of antiandrogen withdrawal had a minimum prostate-specific antigen (PSA) level of 5 ng/dL that was increasing on castration therapy including an antiandrogen. With informed consent, marrow biopsies were obtained to collect prostate tumor. Additional samples were obtained from men enrolled on chemotherapy trials. AR cDNA or DNA was polymerase chain reaction-amplified, cloned, and sequenced. The AR CAG repeat length was recorded. RESULTS: One hundred eighty-four bone marrow biopsies were obtained, and 48 had prostate tumor detected by light microscopy. The ARs from these 48 samples were sequenced. Overall, five (10%) of 48 tumors had mutated ARs. AR point mutations were detected in the hormone-binding domain involved in transcription factor binding. Three mutations were novel in prostate cancer. One tumor sample had a CAG repeat length of 21, compared with germline length of 22 repeats. There was no association between detectability of AR mutations and antiandrogen withdrawal response or survival. CONCLUSION: These data suggest that AR mutations are present in approximately 10% of patients with prostate cancer who experience treatment failure with hormone therapy that included an antiandrogen. Mutations in the AR likely confer a growth advantage for a subset of progressive prostate cancers. Correlation of AR mutation with antiandrogen withdrawal response or survival could not be made.

Authors
Taplin, M-E; Rajeshkumar, B; Halabi, S; Werner, CP; Woda, BA; Picus, J; Stadler, W; Hayes, DF; Kantoff, PW; Vogelzang, NJ; Small, EJ; Cancer and Leukemia Group B Study 9663,
MLA Citation
Taplin, M-E, Rajeshkumar, B, Halabi, S, Werner, CP, Woda, BA, Picus, J, Stadler, W, Hayes, DF, Kantoff, PW, Vogelzang, NJ, Small, EJ, and Cancer and Leukemia Group B Study 9663, . "Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663." J Clin Oncol 21.14 (July 15, 2003): 2673-2678.
PMID
12860943
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
14
Publish Date
2003
Start Page
2673
End Page
2678
DOI
10.1200/JCO.2003.11.102

Analysis of survival data with missing measurements of a time-dependent binary covariate.

The objective of this study was to investigate the influence of the number and timing of a binary time-dependent covariate on the bias using the last-observation carried forward in the proportional hazards model. Under various assumptions of censoring rates, transition probabilities of the time-dependent covariate, sample size, and the log hazard-ratio for the covariate, we empirically examined the impact that the number and timing have on the bias of the estimator of the covariate. An example from the Systolic Hypertension in the Elderly Program was used. Inference on the effect of systolic blood pressure on survival is strongly affected by the number and timing of systolic blood measurements.

Authors
Halabi, S; Wun, C-C; Davis, BR
MLA Citation
Halabi, S, Wun, C-C, and Davis, BR. "Analysis of survival data with missing measurements of a time-dependent binary covariate." J Biopharm Stat 13.2 (May 2003): 253-270.
PMID
12729393
Source
pubmed
Published In
Journal of Biopharmaceutical Statistics
Volume
13
Issue
2
Publish Date
2003
Start Page
253
End Page
270
DOI
10.1081/BIP-120019270

Overview of bladder cancer trials in the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy.

Authors
Small, EJ; Halabi, S; Dalbagni, G; Pruthi, R; Phillips, G; Edelman, M; Bajorin, D; Cancer and Leukemia Group B,
MLA Citation
Small, EJ, Halabi, S, Dalbagni, G, Pruthi, R, Phillips, G, Edelman, M, Bajorin, D, and Cancer and Leukemia Group B, . "Overview of bladder cancer trials in the Cancer and Leukemia Group B." Cancer 97.8 Suppl (April 15, 2003): 2090-2098. (Review)
PMID
12673701
Source
pubmed
Published In
Cancer
Volume
97
Issue
8 Suppl
Publish Date
2003
Start Page
2090
End Page
2098
DOI
10.1002/cncr.11299

Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer.

PURPOSE: To develop and validate a model that can be used to predict the overall survival probability among metastatic hormone-refractory prostate cancer patients (HRPC). PATIENTS AND METHODS: Data from six Cancer and Leukemia Group B protocols that enrolled 1,101 patients with metastatic hormone-refractory adenocarcinoma of the prostate during the study period from 1991 to 2001 were pooled. The proportional hazards model was used to develop a multivariable model on the basis of pretreatment factors and to construct a prognostic model. The area under the receiver operating characteristic curve (ROC) was calculated as a measure of predictive discrimination. Calibration of the model predictions was assessed by comparing the predicted probability with the actual survival probability. An independent data set was used to validate the fitted model. RESULTS: The final model included the following factors: lactate dehydrogenase, prostate-specific antigen, alkaline phosphatase, Gleason sum, Eastern Cooperative Oncology Group performance status, hemoglobin, and the presence of visceral disease. The area under the ROC curve was 0.68. Patients were classified into one of four risk groups. We observed a good agreement between the observed and predicted survival probabilities for the four risk groups. The observed median survival durations were 7.5 (95% confidence interval [CI], 6.2 to 10.9), 13.4 (95% CI, 9.7 to 26.3), 18.9 (95% CI, 16.2 to 26.3), and 27.2 (95% CI, 21.9 to 42.8) months for the first, second, third, and fourth risk groups, respectively. The corresponding median predicted survival times were 8.8, 13.4, 17.4, and 22.80 for the four risk groups. CONCLUSION: This model could be used to predict individual survival probabilities and to stratify metastatic HRPC patients in randomized phase III trials.

Authors
Halabi, S; Small, EJ; Kantoff, PW; Kattan, MW; Kaplan, EB; Dawson, NA; Levine, EG; Blumenstein, BA; Vogelzang, NJ
MLA Citation
Halabi, S, Small, EJ, Kantoff, PW, Kattan, MW, Kaplan, EB, Dawson, NA, Levine, EG, Blumenstein, BA, and Vogelzang, NJ. "Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer." J Clin Oncol 21.7 (April 1, 2003): 1232-1237.
PMID
12663709
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
7
Publish Date
2003
Start Page
1232
End Page
1237
DOI
10.1200/JCO.2003.06.100

A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer.

BACKGROUND: Experimental studies in animals and observational studies in humans suggest that regular aspirin use may decrease the risk of colorectal adenomas, the precursors to most colorectal cancers. METHODS: We conducted a randomized, double-blind trial to determine the effect of aspirin on the incidence of colorectal adenomas. We randomly assigned 635 patients with previous colorectal cancer to receive either 325 mg of aspirin per day or placebo. We determined the proportion of patients with adenomas, the number of recurrent adenomas, and the time to the development of adenoma between randomization and subsequent colonoscopic examinations. Relative risks were adjusted for age, sex, cancer stage, the number of colonoscopic examinations, and the time to a first colonoscopy. The study was terminated early by an independent data and safety monitoring board when statistically significant results were reported during a planned interim analysis. RESULTS: A total of 517 randomized patients had at least one colonoscopic examination a median of 12.8 months after randomization. One or more adenomas were found in 17 percent of patients in the aspirin group and 27 percent of patients in the placebo group (P=0.004). The mean (+/-SD) number of adenomas was lower in the aspirin group than the placebo group (0.30+/-0.87 vs. 0.49+/-0.99, P=0.003 by the Wilcoxon test). The adjusted relative risk of any recurrent adenoma in the aspirin group, as compared with the placebo group, was 0.65 (95 percent confidence interval, 0.46 to 0.91). The time to the detection of a first adenoma was longer in the aspirin group than in the placebo group (hazard ratio for the detection of a new polyp, 0.64; 95 percent confidence interval, 0.43 to 0.94; P=0.022). CONCLUSIONS: Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer.

Authors
Sandler, RS; Halabi, S; Baron, JA; Budinger, S; Paskett, E; Keresztes, R; Petrelli, N; Pipas, JM; Karp, DD; Loprinzi, CL; Steinbach, G; Schilsky, R
MLA Citation
Sandler, RS, Halabi, S, Baron, JA, Budinger, S, Paskett, E, Keresztes, R, Petrelli, N, Pipas, JM, Karp, DD, Loprinzi, CL, Steinbach, G, and Schilsky, R. "A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer." N Engl J Med 348.10 (March 6, 2003): 883-890.
PMID
12621132
Source
pubmed
Published In
The New England journal of medicine
Volume
348
Issue
10
Publish Date
2003
Start Page
883
End Page
890
DOI
10.1056/NEJMoa021633

No relationship between ovarian cancer risk and progesterone receptor gene polymorphism in a population-based, case-control study in North Carolina.

Authors
Lancaster, JM; Wenham, RM; Halabi, S; Calingaert, B; Marks, JR; Moorman, PG; Bentley, RC; Berchuck, A; Schildkraut, JM
MLA Citation
Lancaster, JM, Wenham, RM, Halabi, S, Calingaert, B, Marks, JR, Moorman, PG, Bentley, RC, Berchuck, A, and Schildkraut, JM. "No relationship between ovarian cancer risk and progesterone receptor gene polymorphism in a population-based, case-control study in North Carolina." Cancer Epidemiol Biomarkers Prev 12.3 (March 2003): 226-227.
PMID
12646513
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
12
Issue
3
Publish Date
2003
Start Page
226
End Page
227

Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in metastatic prostate cancer: a nested study within CALGB 9583.

PURPOSE: To determine whether reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating prostate-specific antigen (PSA)-positive cells is a prognostic factor for survival in hormone refractory prostate cancer and to validate the prognostic importance of this test in relation to other known prognostic factors. PATIENTS AND METHODS: A single centralized laboratory received and analyzed whole blood for RT-PCR for PSA for a subset of patients enrolled on two Cancer and Leukemia Group B (CALGB) randomized trials (CALGB 9583 and CALGB 9480). Using 9583, a prognostic model was developed and an independent data set (CALGB 9480) was used to validate the fitted model. RESULTS: Of 162 patients in 9583, 91 (56%) patients were negative for RT-PCR for PSA and 71 (44%) patients were positive. The median survival time was 21 months (95% confidence interval [CI], 18 to 27 months) for RT-PCR-negative patients compared with 11 months (95% CI, 8 to 15 months) for RT-PCR-positive patients (P < or =.001). In multivariable analysis, the hazard ratio (HR) for death was 1.7 (95% CI, 1.2 to 2.4; P =.006) for positive RT-PCR patients compared with negative RT-PCR patients. A fitted model that incorporated RT-PCR for PSA and other factors was used to classify patients from 9480 into one of two risk groups: low or high. We observed good agreement between the observed and predicted survival probabilities for the two risk groups. CONCLUSION: RT-PCR to detect PSA-positive circulating cells is confirmed to be a significant prognostic factor of survival in patients with hormone refractory prostate cancer. This model could be used to stratify patients in randomized phase III trials.

Authors
Halabi, S; Small, EJ; Hayes, DF; Vogelzang, NJ; Kantoff, PW
MLA Citation
Halabi, S, Small, EJ, Hayes, DF, Vogelzang, NJ, and Kantoff, PW. "Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in metastatic prostate cancer: a nested study within CALGB 9583." J Clin Oncol 21.3 (February 1, 2003): 490-495.
PMID
12560440
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
3
Publish Date
2003
Start Page
490
End Page
495
DOI
10.1200/JCO.2003.04.104

Aspirin prevented new colorectal adenomas in patients with previous colorectal cancer

Authors
Sandler, RS; Halabi, S; Baron, JA
MLA Citation
Sandler, RS, Halabi, S, and Baron, JA. "Aspirin prevented new colorectal adenomas in patients with previous colorectal cancer." Evidence-Based Medicine 8.6 (2003): 179--.
Source
scival
Published In
Evidence-based medicine
Volume
8
Issue
6
Publish Date
2003
Start Page
179-
DOI
10.1136/ebm.8.6.179

Overview of bladder cancer trials in the cancer and leukemia group B

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy. © 2003 American Cancer Society.

Authors
Small, EJ; Halabi, S; Dalbagni, G; Pruthi, R; Phillips, G; Edelman, M; Bajorin, D
MLA Citation
Small, EJ, Halabi, S, Dalbagni, G, Pruthi, R, Phillips, G, Edelman, M, and Bajorin, D. "Overview of bladder cancer trials in the cancer and leukemia group B." Cancer 97.8 SUPPL. (2003): 2090-2098.
Source
scival
Published In
Cancer
Volume
97
Issue
8 SUPPL.
Publish Date
2003
Start Page
2090
End Page
2098

Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer

Authors
HALBI, S
MLA Citation
HALBI, S. "Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer." J Clin Oncol 21 (2003): 1232-1237.
Source
cinii-english
Published In
J Clin Oncol
Volume
21
Publish Date
2003
Start Page
1232
End Page
1237
DOI
10.1200/JCO.2003.06.100

Ovulation and ovarian cancer: a comparison of two methods for calculating lifetime ovulatory cycles (United States).

OBJECTIVE: To compare two methods for calculating lifetime ovulatory cycles (LOC) to determine if more detailed menstrual cycle information results in stronger associations with ovarian cancer. METHODS: Using data from 232 cases and 242 controls in a population-based study of ovarian cancer, we compared a standard method for calculating LOC with a second method that had more detailed information on menstrual characteristics. Odds ratios for ovarian cancer by number of LOC were estimated using unconditional logistic regression. RESULTS: The average number of LOC was 29 fewer for the second method that had more detailed menstrual cycle information, as compared to the standard method (p < 0.0001). The difference was due primarily to the second method considering episodes of missed/irregular periods. Associations between LOC and ovarian cancer were weaker for the second method than the standard method. Further analyses suggested that a reduced number of ovulatory cycles due to menstrual irregularity was associated with increased ovarian cancer risk, in contrast to the protective effects observed for fewer ovulatory cycles due to pregnancy or oral contraceptive use. CONCLUSION: Obtaining additional details on menstrual factors that affect LOC, particularly missed or irregular cycles, provides important information on ovarian cancer risk. Our data suggest that episodes of anovulation due to menstrual disturbances should be evaluated separately from anovulation due to pregnancy or oral contraceptive use.

Authors
Moorman, PG; Schildkraut, JM; Calingaert, B; Halabi, S; Vine, MF; Berchuck, A
MLA Citation
Moorman, PG, Schildkraut, JM, Calingaert, B, Halabi, S, Vine, MF, and Berchuck, A. "Ovulation and ovarian cancer: a comparison of two methods for calculating lifetime ovulatory cycles (United States)." Cancer Causes Control 13.9 (November 2002): 807-811.
PMID
12462545
Source
pubmed
Published In
Cancer Causes & Control
Volume
13
Issue
9
Publish Date
2002
Start Page
807
End Page
811

Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480.

PURPOSE: To test the hypothesis that the efficacy and toxicity of suramin in the treatment of patients with hormone-refractory prostate cancer was dose dependent. PATIENTS AND METHODS: Patients were randomized with equal probability to receive low-, intermediate-, or high-dose suramin (total doses 3.192, 5.320, and 7.661 g/m(2), respectively). Overall survival, time to progression, and response rate (prostate-specific antigen [PSA] and objective) for each treatment arm were compared. Relationships between plasma suramin concentrations and response, toxicity, and survival were also evaluated. RESULTS: Three hundred ninety patients were randomized. For the low-, intermediate-, and high-dose arms, the median survival time was 16, 14, and 13 months, respectively (P =.49). The objective response rate was 9%, 7%, and 15%, respectively (P =.10). PSA response rates were 24%, 28%, and 34%, respectively (P =.082). Landmark analyses of a 50% decline in PSA at 20 weeks showed a significant correlation with survival. There was a dose-response relationship between dose and toxicity. After adjusting for treatment arm, the measured suramin concentration was not associated with clinical response, PSA response, survival, or toxicity. CONCLUSION: Although high-dose suramin was associated with higher objective and PSA response rates, these were not statistically significant. Overall, no dose-response relationship was observed for survival or progression-free survival, but toxicity was increased with the higher dose. Patients treated with the low-dose level experienced modest toxicity, making it the preferred arm on this study. The lack of a dose-response relationship and the toxicity profile observed raise questions regarding the utility of suramin, particularly high-dose suramin, as administered on this schedule.

Authors
Small, EJ; Halabi, S; Ratain, MJ; Rosner, G; Stadler, W; Palchak, D; Marshall, E; Rago, R; Hars, V; Wilding, G; Petrylak, D; Vogelzang, NJ
MLA Citation
Small, EJ, Halabi, S, Ratain, MJ, Rosner, G, Stadler, W, Palchak, D, Marshall, E, Rago, R, Hars, V, Wilding, G, Petrylak, D, and Vogelzang, NJ. "Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480." J Clin Oncol 20.16 (August 15, 2002): 3369-3375.
PMID
12177096
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
16
Publish Date
2002
Start Page
3369
End Page
3375
DOI
10.1200/JCO.2002.10.022

A tailored intervention to aid decision-making about hormone replacement therapy.

Authors
McBride, CM; Bastian, LA; Halabi, S; Fish, L; Lipkus, IM; Bosworth, HB; Rimer, BK; Siegler, IC
MLA Citation
McBride, CM, Bastian, LA, Halabi, S, Fish, L, Lipkus, IM, Bosworth, HB, Rimer, BK, and Siegler, IC. "A tailored intervention to aid decision-making about hormone replacement therapy." Am J Public Health 92.7 (July 2002): 1112-1114.
PMID
12084693
Source
pubmed
Published In
American journal of public health
Volume
92
Issue
7
Publish Date
2002
Start Page
1112
End Page
1114

Effects of a mammography decision-making intervention at 12 and 24 months.

BACKGROUND: Most women are not getting regular mammograms, and there is confusion about several mammography-related issues, including the age at which women should begin screening. Numerous groups have called for informed decision making about mammography, but few programs have resulted. Our research is intended to fill this gap. METHODS: We conducted a randomized controlled trial, which ran from 1997 to 2000. Women aged 40 to 44 and 50 to 54, who were enrolled in Blue Cross Blue Shield of North Carolina, were randomly assigned to one of three groups: usual care (UC), tailored print (TP) materials, or TP plus tailored telephone counseling (TP+TC). We assessed the impact of tailored interventions on knowledge about breast cancer and mammography, accuracy of breast cancer risk perceptions, and use of mammography at two time points after intervention-12 and 24 months. RESULTS: At 12 and 24 months, women who received TP+TC had significantly greater knowledge and more accurate breast cancer risk perceptions. Compared to UC, they were 40% more likely to have had mammograms (odds ratio=0.9-2.1). The effect was primarily for women in their 50s. TP had significant effects for knowledge and accuracy, but women who received TP were less likely to have had mammography. CONCLUSIONS: Decision-making interventions, comprised of two tailored print interventions (booklet and newsletter), delivered a year apart, with or without two tailored telephone calls, significantly increased knowledge and accuracy of perceived breast cancer risk at 12 and 24 months post-intervention. The effect on mammography use was significant in bivariate relationships but had a much more modest impact in multivariate analyses.

Authors
Rimer, BK; Halabi, S; Sugg Skinner, C; Lipkus, IM; Strigo, TS; Kaplan, EB; Samsa, GP
MLA Citation
Rimer, BK, Halabi, S, Sugg Skinner, C, Lipkus, IM, Strigo, TS, Kaplan, EB, and Samsa, GP. "Effects of a mammography decision-making intervention at 12 and 24 months." Am J Prev Med 22.4 (May 2002): 247-257.
PMID
11988381
Source
pubmed
Published In
American Journal of Preventive Medicine
Volume
22
Issue
4
Publish Date
2002
Start Page
247
End Page
257

Higher doses of mitoxantrone among men with hormone-refractory prostate carcinoma: a Cancer and Leukemia Group B study.

BACKGROUND: Mitoxantrone in combination with a low-dose glucocorticoid has been shown to produce more favorable outcomes among men with hormone-refractory prostate carcinoma than glucocorticoid alone. Therefore, the authors sought to determine the safety and activity of higher doses of mitoxantrone in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) and a glucocorticoid in preparation for a possible Phase III trial comparing standard to dose-escalated mitoxantrone. METHODS: This Phase II trial enrolled 45 patients from October 1996 to March 1998. Twenty-one patients without pelvic irradiation (Arm I) received 21 mg/m(2) of mitoxantrone every 3 weeks, and 24 patients who had received pelvic irradiation (Arm II) were given 17 mg/m(2) on the same schedule. All patients received 40 mg of hydrocortisone in divided doses daily and GM-CSF at 500 microg/daily for a minimum of 10 days per cycle beginning on the third day of the cycle. RESULTS: In Arm I, 33% of assessable patients achieved a partial response, 50% had a > or = 50% decline in their PSA, and 35% had a > or = 75% decline in PSA values. The comparable numbers in Arm II were 24%, 48%, and 35%, respectively. The median survival times were 12 months in Arm I and 14 months in Arm II. Treatment had to be discontinued in 13% of patients because of thrombocytopenia. No other significant toxicities were encountered. CONCLUSIONS: Higher doses of mitoxantrone (17 and 21 mg/m(2)) were associated with activity comparable to many estramustine combinations and generally were well tolerated. However, because the degree and frequency of thrombocytopenia were greater than that observed with standard dose mitoxantrone (12-14 mg/m(2)), and because the median survival is apparently comparable to standard dose mitoxantrone, this approach to HRPC cannot be recommended for Phase III testing.

Authors
Levine, EG; Halabi, S; Roberts, JD; Kaplan, EB; Rago, R; Atkins, JN; Vogelzang, NJ
MLA Citation
Levine, EG, Halabi, S, Roberts, JD, Kaplan, EB, Rago, R, Atkins, JN, and Vogelzang, NJ. "Higher doses of mitoxantrone among men with hormone-refractory prostate carcinoma: a Cancer and Leukemia Group B study." Cancer 94.3 (February 1, 2002): 665-672.
PMID
11857298
Source
pubmed
Published In
Cancer
Volume
94
Issue
3
Publish Date
2002
Start Page
665
End Page
672

Women's interest in chemoprevention for breast cancer.

BACKGROUND: Chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer. Tamoxifen citrate is the only approved chemopreventive agent for breast cancer. We sought to determine whether women are interested in taking a drug to prevent breast cancer and to assess the relationship between objective and subjective breast cancer risk and interest in chemoprevention. METHODS: We conducted telephone interviews (November 3, 1997, to May 6, 1998) among a community sample of women aged 40 to 45 and 50 to 55 years enrolled in a randomized controlled trial to evaluate the efficacy of a tailored mammography decision aid. Objective breast cancer risk was measured using the 5-year Gail score. Subjective breast cancer risk was measured using perceptions of absolute risk, perceptions of comparative risk, and worry about getting breast cancer. At 12-month follow-up (November 2, 1998, to July 20, 1999), we measured interest in taking a drug to prevent breast cancer. RESULTS: Among the 1273 women surveyed, 23% were interested in taking a drug to prevent breast cancer; 8% were potentially eligible for tamoxifen therapy (5-year Gail score > or = 1.66%). Eligibility for chemoprevention, based on the 5-year Gail score, was not associated with interest in taking a drug to prevent breast cancer. Women who were worried about breast cancer were 3 times more likely to be interested in taking a drug to prevent breast cancer than those who were not worried. CONCLUSION: Women's interest in chemoprevention might arise more from worries about getting breast cancer than from their objective risk factors.

Authors
Bastian, LA; Lipkus, IM; Kuchibhatla, MN; Weng, HH; Halabi, S; Ryan, PD; Skinner, CS; Rimer, BK
MLA Citation
Bastian, LA, Lipkus, IM, Kuchibhatla, MN, Weng, HH, Halabi, S, Ryan, PD, Skinner, CS, and Rimer, BK. "Women's interest in chemoprevention for breast cancer." Arch Intern Med 161.13 (July 9, 2001): 1639-1644.
PMID
11434796
Source
pubmed
Published In
Archives of internal medicine
Volume
161
Issue
13
Publish Date
2001
Start Page
1639
End Page
1644

Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480.

PURPOSE: Plasma vascular endothelial growth factor (VEGF) levels are significantly elevated in patients with hormone-refractory prostate cancer (HRPC) compared with patients with localized disease and have been associated with disease progression in other cancer patient populations. Therefore, we measured VEGF levels in plasma prospectively collected from patients enrolled in Cancer and Leukemia Group B 9480, an intergroup study of suramin in patients with HRPC, to determine whether these levels had prognostic significance. EXPERIMENTAL DESIGN: Pretreatment plasma was collected from patients with HRPC enrolled in Cancer and Leukemia Group B 9480. In a subset of samples representative of the entire cohort, plasma VEGF levels were determined in duplicate using a Quantiglo chemiluminescent ELISA kit (R&D Systems, Minneapolis, MN). Statistical analyses were performed to determine the correlation between pretreatment plasma VEGF levels and time of overall survival. The proportional hazards model was used to assess the prognostic significance of various cut points in multivariate models. RESULTS: Plasma VEGF levels in this population ranged from 4-885 pg/ml, with a median level of 83 pg/ml. As a continuous variable, plasma VEGF levels inversely correlated with survival time (P = 0.002). Using various exploratory cut points, plasma VEGF levels appeared to correlate with survival. In multivariate models in which other prognostic factors (serum prostate-specific antigen, alkaline phosphatase, evidence of measurable disease, and hemoglobin) were included, plasma VEGF levels were significant at various cut points tested. CONCLUSION: Although these data are exploratory and need to be confirmed in an independent data set, they suggest that VEGF may have clinical significance in patients with HRPC.

Authors
George, DJ; Halabi, S; Shepard, TF; Vogelzang, NJ; Hayes, DF; Small, EJ; Kantoff, PW; Cancer and Leukemia Group B 9480,
MLA Citation
George, DJ, Halabi, S, Shepard, TF, Vogelzang, NJ, Hayes, DF, Small, EJ, Kantoff, PW, and Cancer and Leukemia Group B 9480, . "Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480." Clin Cancer Res 7.7 (July 2001): 1932-1936.
PMID
11448906
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
7
Issue
7
Publish Date
2001
Start Page
1932
End Page
1936

Age at natural menopause and the risk of epithelial ovarian cancer.

OBJECTIVE: To investigate the relationship between age at natural menopause and risk of developing epithelial ovarian cancer. METHODS: Using data from six population-based, case-control studies conducted in the United States, age at natural menopause among 1411 women with epithelial ovarian cancer and 6380 control subjects were analyzed using survival analysis methods, including Kaplan-Meier and proportional hazards models. Subjects ranged from 20 to 81 years of age. RESULTS: The median age at natural menopause was 50 years among cases compared with 51 years among controls, a difference of borderline statistical significance (P =.06). The hazard ratio for the relationship between case-control status and age at natural menopause was 1.09 (95% confidence interval 0.99, 1.20). Controlling for potential confounders including parity, oral contraceptive use, tubal ligation, smoking, and body mass index did not appreciably change this association. There was little evidence of an association between early age at natural menopause and early onset ovarian cancer (diagnosis age under 48 years). CONCLUSION: We observed a weak association between ovarian cancer risk and age at natural menopause and, among women with early onset disease, there was little evidence to suggest that early menopause is related to ovarian cancer. Thus, there seems little need for increased surveillance or screening for ovarian cancer among women with early natural menopause.

Authors
Schildkraut, JM; Cooper, GS; Halabi, S; Calingaert, B; Hartge, P; Whittemore, AS
MLA Citation
Schildkraut, JM, Cooper, GS, Halabi, S, Calingaert, B, Hartge, P, and Whittemore, AS. "Age at natural menopause and the risk of epithelial ovarian cancer." Obstet Gynecol 98.1 (July 2001): 85-90. (Review)
PMID
11430962
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
98
Issue
1
Publish Date
2001
Start Page
85
End Page
90

Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in men with hormone-refractory prostate cancer.

PURPOSE: To evaluate the prognostic significance of reverse transcriptase polymerase chain reaction (RT-PCR) detection of prostate-specific antigen (PSA) mRNA in the blood of men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Peripheral blood was obtained from 193 men enrolled on Cancer and Leukemia Group B Study 9480, a prospective randomized comparison of three doses of suramin. RNA was isolated from the samples and assayed for the presence of PSA transcripts by RT-PCR. RESULTS: RNA could be isolated in 156 (83%) of samples. PSA transcripts as measured by RT-PCR were detectable in 75 (48%) of the 156 patients. The median survival for those patients in whom no transcripts were detectable was 18 months (95% confidence interval [CI], 14 to 22 months) compared with 13 months (95% CI, 11 to 15 months) (P =.004) for those in whom transcripts were detectable. In a multivariate analysis in which other factors predictive of survival were used, RT-PCR for PSA provided independent prognostic information. CONCLUSION: RT-PCR for PSA predicts survival duration in a population of men with HRPC.

Authors
Kantoff, PW; Halabi, S; Farmer, DA; Hayes, DF; Vogelzang, NA; Small, EJ
MLA Citation
Kantoff, PW, Halabi, S, Farmer, DA, Hayes, DF, Vogelzang, NA, and Small, EJ. "Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in men with hormone-refractory prostate cancer." J Clin Oncol 19.12 (June 15, 2001): 3025-3028.
PMID
11408497
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
19
Issue
12
Publish Date
2001
Start Page
3025
End Page
3028
DOI
10.1200/JCO.2001.19.12.3025

Comparison of two methods for calculating lifetime ovulatory cycles.

Authors
Moorman, PG; Calingaert, B; Vine, M; Halabi, S; Berchuck, A; Schildkraut, JM
MLA Citation
Moorman, PG, Calingaert, B, Vine, M, Halabi, S, Berchuck, A, and Schildkraut, JM. "Comparison of two methods for calculating lifetime ovulatory cycles." AMERICAN JOURNAL OF EPIDEMIOLOGY 153.11 (June 1, 2001): S138-S138.
Source
wos-lite
Published In
American Journal of Epidemiology
Volume
153
Issue
11
Publish Date
2001
Start Page
S138
End Page
S138

Age at natural menopause and the risk of developing invasive epithelial ovarian cancer.

Authors
Halabi, S; Schildkraut, JM; Cooper, GS; Calingaert, B; Hartge, P; Whittemore, AS
MLA Citation
Halabi, S, Schildkraut, JM, Cooper, GS, Calingaert, B, Hartge, P, and Whittemore, AS. "Age at natural menopause and the risk of developing invasive epithelial ovarian cancer." AMERICAN JOURNAL OF EPIDEMIOLOGY 153.11 (June 1, 2001): S111-S111.
Source
wos-lite
Published In
American Journal of Epidemiology
Volume
153
Issue
11
Publish Date
2001
Start Page
S111
End Page
S111

The short-term impact of tailored mammography decision-making interventions.

BACKGROUND: We assessed the short-term impact of decision-making interventions on knowledge about mammography, accuracy of women's breast cancer risk perceptions, attitudes toward mammography, satisfaction with decisions, and mammography use since the intervention. METHODS: The study was conducted among women who were members of Blue Cross Blue Shield of North Carolina and were in their 40s or 50s at the time the study began in 1997. Women were randomly assigned to usual care (UC), tailored print booklets (TP) alone, or TP plus telephone counseling (TP+TC ). RESULTS: 12-month interviews were completed by 1127 women to assess short-term intervention effects. Generally, women who received TP+TC were significantly more knowledgeable about mammography and breast cancer risk and were more accurate in their breast cancer risk perceptions than women in the TP and UC groups. They also were more likely to have had a mammogram since the baseline interview. In multivariable analyses, we found significant benefits of the combination of TP+TC compared to TP and to UC for knowledge, accuracy of risk perceptions, and mammography use. DISCUSSION: For complex decision-making tasks, such as women's decisions about mammography in the face of controversy, the combination of TP and TC may be more effective than TP alone, and certainly more effective than UC. It is critical that investigators determine the topics for which TP is appropriate and the situations that require additional supportive interventions.

Authors
Rimer, BK; Halabi, S; Sugg Skinner, C; Kaplan, EB; Crawford, Y; Samsa, GP; Strigo, TS; Lipkus, IM
MLA Citation
Rimer, BK, Halabi, S, Sugg Skinner, C, Kaplan, EB, Crawford, Y, Samsa, GP, Strigo, TS, and Lipkus, IM. "The short-term impact of tailored mammography decision-making interventions." Patient Educ Couns 43.3 (June 2001): 269-285.
PMID
11384825
Source
pubmed
Published In
Patient Education and Counseling
Volume
43
Issue
3
Publish Date
2001
Start Page
269
End Page
285

Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B.

PURPOSE: To investigate the combination of docetaxel, estramustine (EM), and low-dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Combinations of EM with other antimitotic agents such as docetaxel are synergistic in vitro and show significant clinical activity in patients with HRPC. We studied intravenous administration of docetaxel 70 mg/m(2), oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. RESULTS: Of the 47 men enrolled onto this multicenter cooperative group study, 46 were assessable for response and/or toxicity. In the 24 patients with measurable disease, there were three complete and nine partial responses for a measurable disease response rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the 44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30 (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease in PSA. The combined measurable disease and biochemical response rate in all 46 assessable patients was 54% (three complete responses, 22 partial responses, 95% CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of febrile neutropenia. Other common but mild adverse effects included malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of thromboembolic events during therapy was 9%. With a median follow-up of 17 months, the median survival was 20 months. The median time to disease progression was 8 months for all patients, and 10 months for those with measurable disease. CONCLUSION: This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.

Authors
Savarese, DM; Halabi, S; Hars, V; Akerley, WL; Taplin, ME; Godley, PA; Hussain, A; Small, EJ; Vogelzang, NJ
MLA Citation
Savarese, DM, Halabi, S, Hars, V, Akerley, WL, Taplin, ME, Godley, PA, Hussain, A, Small, EJ, and Vogelzang, NJ. "Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: a final report of CALGB 9780. Cancer and Leukemia Group B." J Clin Oncol 19.9 (May 1, 2001): 2509-2516.
PMID
11331330
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
19
Issue
9
Publish Date
2001
Start Page
2509
End Page
2516
DOI
10.1200/JCO.2001.19.9.2509

Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: a cancer and leukemia group B study.

Better prognostic markers are needed for hormone-refractory prostate cancer (HRPC) patients. No single biochemical or clinical parameter can reliably predict patient response to therapy or rapidity of disease progression. Peptide factors involved in major cancer growth pathways, such as tumor angiogenesis, are attractive candidates as markers of low- and high-risk HRPC patients. We analyzed prospectively collected urine specimens from 100 of 390 HRPC patients undergoing therapy with the growth factor antagonist suramin as part of CALGB 9480. Levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assessed from day 1 of therapy (D1) and day 29 (D29) urine samples from this subset of 100 randomly selected patients. Growth factor levels were determined by standardized ELISA microtiter plate assays from a commercial (bFGF) or proprietary (VEGF) source. Pretreatment urine VEGF levels were predictive of survival. In univariate analysis, patients whose baseline urine VEGF level was < or =28 pg/ml (the median level) had an average survival of 17 months; those with baseline VEGF >28 pg/ml had a significantly shorter survival of 10 months (P = 0.024). This difference corresponded to a 60% increased risk of dying for the higher urine VEGF patients (hazard ratio, 1.62; P = 0.03) and remained significant in multivariate analysis (hazard ratio, 1.72, P = 0.02). No significant correlations between urine bFGF level or change in bFGF levels and survival were found. These results support the notion that certain peptide growth factor-mediated, mitogenic pathways are important in HRPC and that their levels can predict outcome.

Authors
Bok, RA; Halabi, S; Fei, DT; Rodriquez, CR; Hayes, DF; Vogelzang, NJ; Kantoff, P; Shuman, MA; Small, EJ
MLA Citation
Bok, RA, Halabi, S, Fei, DT, Rodriquez, CR, Hayes, DF, Vogelzang, NJ, Kantoff, P, Shuman, MA, and Small, EJ. "Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: a cancer and leukemia group B study." Cancer Res 61.6 (March 15, 2001): 2533-2536.
PMID
11289126
Source
pubmed
Published In
Cancer Research
Volume
61
Issue
6
Publish Date
2001
Start Page
2533
End Page
2536

Use of vitamins, minerals, and nutritional supplements by participants in a chemoprevention trial.

BACKGROUND: The growing use of vitamins, minerals, and nutritional supplements has the potential to influence the design and interpretation of randomized controlled trials of chemopreventive agents. To the extent that these complementary agents are effective, they could limit the ability of trials to demonstrate an effect of the agents under study. METHODS: During the course of a colorectal neoplasia chemoprevention trial using aspirin in a group of colorectal carcinoma survivors, the authors obtained information on the use of vitamins, minerals, and supplements at baseline and every 6 months. The information from 622 study participants was categorized and enumerated. RESULTS: One or more supplements were used at some time by 341 (55%) subjects. Among those who took supplements, 66% took more than 1 and 13% took 5 or more. The mean number of supplements taken was 2.6 (1.7 standard deviation). Vitamins were the most commonly used (49%), followed by minerals (22%), botanicals (13%), and others (5%). Among the vitamins, the most frequently used were multivitamins (38% of subjects), vitamin C (18%), and vitamin E (22%). Calcium (16%) was the most frequent mineral. Among users, there were no differences in supplement use by age or gender. CONCLUSIONS: Supplement use was common among colorectal carcinoma survivors enrolled in a prevention trial. Investigators should record the information on supplement use so that the possible impact of the supplements on trial endpoints can be evaluated. It may be necessary to increase the size of studies if many of the subjects take potentially effective supplements.

Authors
Sandler, RS; Halabi, S; Kaplan, EB; Baron, JA; Paskett, E; Petrelli, NJ
MLA Citation
Sandler, RS, Halabi, S, Kaplan, EB, Baron, JA, Paskett, E, and Petrelli, NJ. "Use of vitamins, minerals, and nutritional supplements by participants in a chemoprevention trial." Cancer 91.5 (March 1, 2001): 1040-1045.
PMID
11251957
Source
pubmed
Published In
Cancer
Volume
91
Issue
5
Publish Date
2001
Start Page
1040
End Page
1045

De novo establishment and cost-effectiveness of papanicolaou cytology screening services in the socialist republic of Vietnam

BACKGROUND. Cervical carcinoma is the leading cause of cancer-related death among women in the developing world. The absence of cervical screening in Vietnam and other developing countries is due in large part to the perceived expense of implementing Papanicolaou cytology screening services, although, to the authors' knowledge, the cost-effectiveness of establishing such services has never been studied in a developing country. METHODS. Using decision analytic methods, the authors assessed cost-effectiveness of Pap screening from a societal perspective in Vietnam, the world's 9th most populous developing country (estimated 1999 population, 79 million). Outcomes measured included life expectancy, cervical carcinoma incidence, cost per woman, and cost-effectiveness. RESULTS. Total costs to establish a nationwide 5-year interval Pap screening program in Vietnam will average less than $148,400 annually during the 10-year time period assumed necessary to develop the program and may be considerably lower if only high risk geographic areas are targeted. Maintenance costs will average less than $0.092 annually per woman in the target screening population. Assuming 70% program participation, cervical carcinoma incidence will decrease from 26 in 100,000 to 14.8 in 100,000, and cost-effectiveness will be $725 per discounted life-year. Several assumptions used in this analysis constitute biases against the effectiveness of Pap screening, which in reality may be significantly more cost-effective than reported here. CONCLUSIONS. Contrary to widespread belief, Pap screening in developing countries such as Vietnam is extraordinarily inexpensive and appears to be cost-effective. Because prospects are uncertain regarding useful alternatives to the Pap test, the evidence-based argument for establishing conventional Pap screening services in developing countries such as Vietnam is compelling. Population-based conventional Pap screening services have been established de novo in Vietnam and are now operational. © 2001 American Cancer Society.

Authors
Sandler, RS; Halabi, S; Kaplan, EB; Baron, JA; Paskett, E; Petrelli, NJ
MLA Citation
Sandler, RS, Halabi, S, Kaplan, EB, Baron, JA, Paskett, E, and Petrelli, NJ. "De novo establishment and cost-effectiveness of papanicolaou cytology screening services in the socialist republic of Vietnam." Cancer 91.5 (2001): 928-939.
PMID
11251944
Source
scival
Published In
Cancer
Volume
91
Issue
5
Publish Date
2001
Start Page
928
End Page
939
DOI
10.1002/1097-0142(20010301)91:5<928::AID-CNCR1082>3.0.CO;2-S

Serum prostate specific antigen as a predictor of survival in prostate cancer patients treated with second-line hormonal therapy (CALGB 9181)

Objectives: To explore whether serum prostate specific antigen (PSA) decline can be used as a prognostic factor for survival among patients with androgen-independent prostate cancer (AIPC) who are treated with a secondary hormonal therapy, megestrol acetate. Materials and Methods: One hundred forty-nine patients were randomized with equal probability to either low-dose (160 mg/day) or high-dose (640 mg/day) megestrol acetate. Patients were stratified on performance status (0-1, or 2) and on disease measurability (measurable, or evaluable disease). Results: Patients with high pretreatment PSA (≥95 ng/ml) had worse survival times than patients with low PSA (<95), with a hazard ratio of 1.6 (p = 0.003). The median survival times for patients with a ≥50% reduction in PSA at 8 weeks and those patients without a 50% reduction were 15 and 11 months, respectively (p = 0.763). A landmark analysis at 8 weeks showed that a PSA decline was significantly associated with survival. The survival time for patients whose PSA dropped below the pretreatment levels (median = 15 months) were significantly longer than for patients who did not have a decline in PSA (median = 9 months, p = 0.031). Similar significant results were observed between PSA reduction and survival when landmark analyses were performed at 12 and 16 weeks. PSA changes during the first 45 days after the initiation of therapy were significantly related to survival. The median survival time for patients whose PSA doubled during the first 45 days after treatment and for patients whose PSA did not double during the first 45 days were 10 and 14 months, respectively (p = 0.020). Conclusions: PSA decline is significantly associated with longer survival times in prostate patients treated with secondary hormonal manipulation. Longer survival time is observed among the following AIPC patients: 1) those whose pretreatment PSA were <95 ng/ml: 2) those whose PSA decline was >0% from baseline; and 3) those whose PSA did not double during the first 45 days of therapy. If these observations are generalizeable, PSA decline as a criterion of response could be used to rapidly approve new agents in patients treated with second-line hormonal therapy.

Authors
Halabi, S; Conaway, MR; Small, EJ; Vogelzang, NJ; Dawson, NA
MLA Citation
Halabi, S, Conaway, MR, Small, EJ, Vogelzang, NJ, and Dawson, NA. "Serum prostate specific antigen as a predictor of survival in prostate cancer patients treated with second-line hormonal therapy (CALGB 9181)." Prostate Journal 3.1 (2001): 18-25.
Source
scival
Published In
Prostate Journal
Volume
3
Issue
1
Publish Date
2001
Start Page
18
End Page
25
DOI
10.1046/j.1525-1411.2001.31003.x

Factors associated with repeat mammography screening.

BACKGROUND: Even organizations with differing mammography recommendations agree that regular repeat screening is required for mortality reduction. However, most studies have focused on one-time screening rather than repeat adherence. We compare trends in beliefs and health-related behaviors among women screened and adherent to the National Cancer Institute's screening mammography recommendations (on schedule), those screened at least once and nonadherent (off schedule), and those never screened. METHODS: Our data are from a baseline telephone interview conducted among 1,287 female members of Blue Cross Blue Shield of North Carolina who were aged either 40 to 44 years or 50 to 54 years. RESULTS: The 3 groups differed significantly on beliefs and health-related behaviors, with the off-schedule group almost consistently falling between the on-schedule and never screened groups. Off-schedule women were more likely than on-schedule women, but less likely than those never screened, to not have a clinical breast examination within 12 months, to be ambivalent about screening mammography, to be confused about screening guidelines, and to not be advised by a physician to get a mammogram in the past 2 years. Off-schedule women perceived their breast cancer risk as lower and were less likely to be up to date with other cancer screening tests. CONCLUSIONS: Our findings suggest that women who are off schedule are in need of mammography-promoting interventions, including recommendations from and discussion with their health care providers. Because they are more positive and knowledgeable about mammography than women who have never been screened, they may benefit from brief interventions from health care providers that highlight the importance of repeat screening.

Authors
Halabi, S; Skinner, CS; Samsa, GP; Strigo, TS; Crawford, YS; Rimer, BK
MLA Citation
Halabi, S, Skinner, CS, Samsa, GP, Strigo, TS, Crawford, YS, and Rimer, BK. "Factors associated with repeat mammography screening." J Fam Pract 49.12 (December 2000): 1104-1112.
PMID
11132060
Source
pubmed
Published In
Journal of Family Practice
Volume
49
Issue
12
Publish Date
2000
Start Page
1104
End Page
1112

Relationships among breast cancer perceived absolute risk, comparative risk, and worries.

When trying to predict breast cancer screening, it may be important to understand the relationships between perceived breast cancer risks and worries about getting breast cancer. This study examines the extent to which women's worries about breast cancer correlate with perceptions of both absolute (assessment of own) and comparative (self versus other) 10-year and lifetime risks. As part of a larger randomized intervention trial concerning hormone replacement therapy, 581 women participated in a telephone baseline survey to assess their perceptions of breast cancer risks and worries. Worries about getting breast cancer in the next 10 years and in one's lifetime were related positively to both absolute and comparative 10-year and lifetime risks. The magnitude of these relationships did not differ by time frame. Worry about breast cancer is a function of both how a woman views her own risk and how she compares her risk with that of other women. Some practitioners may encourage women to get screened for breast cancer by using emotional appeals, such as heightening women's worries about breast cancer by using risk information. Our data suggest that they should give careful consideration how best to combine, if at all, information about absolute and comparative risks. For example, if the motivation to screen is based on a sequential assessment of risk beginning with comparative and then absolute risk, creating communications that heighten perceived risk on both of these risk dimensions may be needed to evoke sufficient worry to initiate breast cancer screening.

Authors
Lipkus, IM; Kuchibhatla, M; McBride, CM; Bosworth, HB; Pollak, KI; Siegler, IC; Rimer, BK
MLA Citation
Lipkus, IM, Kuchibhatla, M, McBride, CM, Bosworth, HB, Pollak, KI, Siegler, IC, and Rimer, BK. "Relationships among breast cancer perceived absolute risk, comparative risk, and worries." Cancer Epidemiol Biomarkers Prev 9.9 (September 2000): 973-975.
PMID
11008917
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
9
Issue
9
Publish Date
2000
Start Page
973
End Page
975

The impact of abnormal mammograms on psychosocial outcomes and subsequent screening.

Few studies have examined the impact of abnormal mammograms on subsequent mammography screening and psychosocial outcomes specifically as a function of the length of time that has passed since the abnormal test result. This cross-sectional report compared breast cancer screening practices and psychosocial outcomes among three groups of women. These groups were women who (1) never had an abnormal mammogram, (2) had an abnormal mammogram 2 or more years prior to the study's baseline interview, and (3) had an abnormal mammogram within 2 years prior to the study's baseline interview. Women who had an abnormal mammogram at least 2 years prior to the baseline interview expressed greater 10-year and lifetime risks of getting breast cancer than women who never had an abnormal mammogram. Women who had abnormal mammograms, independent of when they occurred, were substantially more worried about getting breast cancer than were women who never had abnormal mammograms. Women who had an abnormal mammogram within 2 years prior to the baseline interview were more likely to be on schedule for mammography, compared with women who never had an abnormal mammogram.

Authors
Lipkus, IM; Halabi, S; Strigo, TS; Rimer, BK
MLA Citation
Lipkus, IM, Halabi, S, Strigo, TS, and Rimer, BK. "The impact of abnormal mammograms on psychosocial outcomes and subsequent screening." Psychooncology 9.5 (September 2000): 402-410.
PMID
11038478
Source
pubmed
Published In
Psycho-Oncology
Volume
9
Issue
5
Publish Date
2000
Start Page
402
End Page
410

Validation of the surveillance system for tuberculosis in Botswana.

SETTING: Gaborone and Francistown, Botswana, where surveillance data in the 1997 Electronic Tuberculosis (TB) Register suggest that 39% of pulmonary TB patients did not have pre-treatment sputum smear microscopy performed. OBJECTIVE: To determine the proportion of patients with reportedly missing pre-treatment sputum smear results in 1997 who had smears examined, and to identify stages in the system where results were lost. METHODS: Patients with pulmonary TB in 1997 who were missing pre-treatment sputum smear results in the Electronic TB Register were cross-matched with laboratory records; medical records were reviewed. RESULTS: Of 374 patients with pre-treatment sputum smear results missing, 224 (60%) actually had had a sputum smear examined in the laboratory. The proportion of pulmonary TB patients in Gaborone and Francistown who did not have sputum examined was therefore 16% instead of 39%. Most missing results (69%) had not been transcribed from the laboratory results onto the TB Treatment Card. Patients who had a negative smear result or who sought care at a clinic that was different from where their diagnostic evaluation had been initiated were more likely to have missing results. CONCLUSIONS: The actual performance of the Botswana National TB Programme with respect to sputum microscopy examination is much better than surveillance indicators suggest. In addition to sputum collection, proper recording of results needs reinforcement among health care workers to improve routine performance indicators.

Authors
Alpers, L; Chrouser, K; Halabi, S; Moeti, T; Reingold, A; Binkin, N; Kenyon, T
MLA Citation
Alpers, L, Chrouser, K, Halabi, S, Moeti, T, Reingold, A, Binkin, N, and Kenyon, T. "Validation of the surveillance system for tuberculosis in Botswana." Int J Tuberc Lung Dis 4.8 (August 2000): 737-743.
PMID
10949325
Source
pubmed
Published In
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Volume
4
Issue
8
Publish Date
2000
Start Page
737
End Page
743

Maximizing the motivational impact of feedback of lung cancer susceptibility on smokers' desire to quit.

This two-by-two factorially designed study evaluate approaches for communicating feedback of lung cancer susceptibility to smokers as a method for motivating smoking cessation. The study factors were: method of communicating feedback (by mail with telephone follow-up or in-person) and carbon monoxide feedback (yes or no). One-hundred-forty-four smokers were stratified on race and randomized to one of four conditions. Participants were surveyed at baseline and 2-month follow-up. Polymerase chain reaction (PCR) testing for the absence of the glutathione S transferase mu (GSTM1) gene was the susceptibility marker. Regardless of counseling method or carbon monoxide (CO) feedback, the majority (90%) of smokers accurately recalled the test result and 66% accurately interpreted the meaning of the test result. Smokers who received their result in person were significantly less likely to have read the result booklet than those in the telephone counseling group (OR = .28, 95%; CI .12-.62; p < .05). Neither counseling method nor CO feedback increased smokers' perceived risks for lung cancer. However, at the counseling session those who received in-person counseling were significantly less frightened by the test result than those who received telephone counseling (OR = .42, 95%; CI .20-86; p < .05) and at the 2-month follow-up those who received a CO test were significantly less frightened by their susceptibility result (OR = .40, 95%; CI .17-.92; p < .05) than those who did not have a CO test. Evaluation of further refinements in communicating the meaning of susceptibility results to motivate smoking cessation is warranted.

Authors
McBride, CM; Halabi, S; Bepler, G; Lyna, P; McIntyre, L; Lipkus, I; Albright, J; O'Briant, K
MLA Citation
McBride, CM, Halabi, S, Bepler, G, Lyna, P, McIntyre, L, Lipkus, I, Albright, J, and O'Briant, K. "Maximizing the motivational impact of feedback of lung cancer susceptibility on smokers' desire to quit." J Health Commun 5.3 (July 2000): 229-241.
PMID
11185023
Source
pubmed
Published In
Journal of Health Communication
Volume
5
Issue
3
Publish Date
2000
Start Page
229
End Page
241
DOI
10.1080/10810730050131406

A randomized study comparing standard versus moderately high dose megestrol acetate for patients with advanced prostate carcinoma: cancer and leukemia group B study 9181.

BACKGROUND: Megestrol acetate (MA) is a synthetic progestin with reported activity in both hormone-sensitive and hormone-refractory prostate carcinoma (HRPC). Based on limited data suggesting a possible dose-response effect, a trial was initiated to compare standard versus moderately high dose MA in HRPC. METHODS: One hundred forty-nine men with hormone-refractory prostate carcinoma were randomized to receive oral MA either at 160 mg/day (low dose) or 640 mg/day (high dose). Patients were stratified by performance status and measurable versus evaluable disease. The primary end point was tumor response. Secondary end points were survival, quality-of-life measures, and prostate specific antigen (PSA) decline. RESULTS: The median survival times of 11.2 months for patients who received the low dose and 12.1 months for patients who received the high dose therapy were not significantly different. Best response was equivalent in the 2 arms: 2 partial responses and 22 patients with stable disease for the 160 mg/day dose, and 1 partial response and 28 patients with stable disease for the 640 mg/day dose. A greater than 50% decline in PSA occurred in 13.8% and 8.8% of patients in the low and high dose treatment arms, respectively. There were no differences in the toxicity or quality-of-life outcomes between the two arms. Poorer performance status (2 vs. 0-1), greater than 5% weight loss, higher baseline PSA, and measurable disease all predicted shorter survival. CONCLUSIONS: MA has limited activity in hormone-refractory prostate carcinoma, and there is no apparent dose-response correlation.

Authors
Dawson, NA; Conaway, M; Halabi, S; Winer, EP; Small, EJ; Lake, D; Vogelzang, NJ
MLA Citation
Dawson, NA, Conaway, M, Halabi, S, Winer, EP, Small, EJ, Lake, D, and Vogelzang, NJ. "A randomized study comparing standard versus moderately high dose megestrol acetate for patients with advanced prostate carcinoma: cancer and leukemia group B study 9181." Cancer 88.4 (February 15, 2000): 825-834.
PMID
10679652
Source
pubmed
Published In
Cancer
Volume
88
Issue
4
Publish Date
2000
Start Page
825
End Page
834

Increased weight & body fatness associated with chemotherapy for breast cancer ... & what can be done?

Authors
Demark-Wahnefried, W; Halabi, S; Hars, V; Winer, E; Marcom, PK; Blackwell, K; Harris, L; Rimer, BK
MLA Citation
Demark-Wahnefried, W, Halabi, S, Hars, V, Winer, E, Marcom, PK, Blackwell, K, Harris, L, and Rimer, BK. "Increased weight & body fatness associated with chemotherapy for breast cancer .. & what can be done?." CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION 9.2 (February 2000): 236-236.
Source
wos-lite
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
9
Issue
2
Publish Date
2000
Start Page
236
End Page
236

Prognostic factors in early-onset epithelial ovarian cancer: a population-based study.

OBJECTIVE: To investigate the clinical prognostic factors that influence ovarian cancer survival in women with early-onset epithelial ovarian cancer using population-based data. METHODS: Subjects in the current study were from a population-based series of 197 patients with invasive ovarian cancer and 60 patients with ovarian cancer of low malignant potential who were identified from the Cancer and Steroid Hormone study. All subjects were between 20 and 54 years of age at diagnosis for ovarian cancer. Epidemiologic data were obtained from each participant. Immunohistochemical staining was performed to assess p53 expression in paraffin-embedded ovarian cancers. Univariate and multivariate analyses for survival were conducted using the proportional hazards model to test the prognostic significance of several clinicopathologic factors among subjects. RESULTS: Among women with invasive tumors, the proportional hazards model revealed that advanced stage at diagnosis [hazard ratio = 4.1, 95% confidence interval (CI) = 2.5, 6.6], age at diagnosis 46-54 (hazard ratio = 2.0, 95% CI = 1.3, 3.0), and overexpression of p53 (hazard ratio = 1.5, 95% CI = 1.1, 2.3) were significantly associated with decreased survival. CONCLUSION: These results provide evidence that stage, age, and p53 overexpression are independent predictors of decreased survival in women with invasive ovarian cancer diagnosed younger than age 55. Further investigation of the effect of age at diagnosis on the relationship between p53 overexpression and ovarian cancer survival is warranted.

Authors
Schildkraut, JM; Halabi, S; Bastos, E; Marchbanks, PA; McDonald, JA; Berchuck, A
MLA Citation
Schildkraut, JM, Halabi, S, Bastos, E, Marchbanks, PA, McDonald, JA, and Berchuck, A. "Prognostic factors in early-onset epithelial ovarian cancer: a population-based study." Obstet Gynecol 95.1 (January 2000): 119-127.
PMID
10636514
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
95
Issue
1
Publish Date
2000
Start Page
119
End Page
127

Can tailored interventions increase mammography use among HMO women?

BACKGROUND: Telephone counseling and tailored print communications have emerged as promising methods for promoting mammography screening. However, there has been little research testing, within the same randomized field trial, of the efficacy of these two methods compared to a high-quality usual care system for enhancing screening. This study addressed the question: Compared to usual care, is tailored telephone counseling more effective than tailored print materials for promoting mammography screening? DESIGN: Three-year randomized field trial. PARTICIPANTS: One thousand ninety-nine women aged 50 and older recruited from a health maintenance organization in North Carolina. INTERVENTION: Women were randomized to 1 of 3 groups: (1) usual care, (2) tailored print communications, and (3) tailored telephone counseling. MAIN OUTCOME: Adherence to mammography screening based on self-reports obtained during 1995, 1996, and 1997. RESULTS: Compared to usual care alone, telephone counseling promoted a significantly higher proportion of women having mammograms on schedule (71% vs 61%) than did tailored print (67% vs 61%) but only after the first year of intervention (during 1996). Furthermore, compared to usual care, telephone counseling was more effective than tailored print materials at promoting being on schedule with screening during 1996 and 1997 among women who were off-schedule during the previous year. CONCLUSIONS: The effects of the intervention were most pronounced after the first intervention. Compared to usual care, telephone counseling seemed particularly effective at promoting change among nonadherent women, the group for whom the intervention was developed. These results suggest that telephone counseling, rather than tailored print, might be the preferred first-line intervention for getting nonadherent women on schedule for mammography screening. Many questions would have to be answered about why the tailored print intervention was not more powerful. Nevertheless, it is clear that additional interventions will be needed to maintain women's adherence to mammography. Medical Subject Headings (MeSH): mammography screening, telephone counseling, tailored print communications, barriers.

Authors
Lipkus, IM; Rimer, BK; Halabi, S; Strigo, TS
MLA Citation
Lipkus, IM, Rimer, BK, Halabi, S, and Strigo, TS. "Can tailored interventions increase mammography use among HMO women?." Am J Prev Med 18.1 (January 2000): 1-10.
PMID
10808977
Source
pubmed
Published In
American Journal of Preventive Medicine
Volume
18
Issue
1
Publish Date
2000
Start Page
1
End Page
10

Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473.

The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of fish oil fatty acid capsules containing omega-3 fatty acid ethyl esters. Twenty-two patients with neoplastic disease not amenable to curative therapy who had lost 2% of body weight over a previous 1 month time period were given an escalating dose of fish oil fatty acids. The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation. This means that a 70-kg patient can generally tolerate up to 21 1-g capsules/day containing 13.1 g of eicosapentaenoic acid + docosahexaenoic acid, the two major omega-3 fatty acids. Dose-limiting toxicity was gastrointestinal, mainly diarrhea, and a poorly described toxicity designated as "unable to tolerate in esophagus or stomach." A patient with chronic lymphocytic leukemia taking the fish oil provided an unusual opportunity to perform a detailed biochemical study of the effect of fish oil capsules on the lipids of malignant cells at several sequential time points in treatment. Studies of the malignant lymphocytes, serum, and whole blood of this one patient revealed an increase in eicosapentaenoic acid, the major component of the fish oil capsules, during fish oil capsule treatment. This study provides a scientific basis for the selection of omega-3 fatty acid doses for future studies in cancer. The maximum tolerated dose found is considerably higher than anticipated from published studies of many human diseases. The observation of a modification of the lipids of leukemic cells, serum, and blood in a patient with chronic leukemia provides a biochemical basis for a possible effect of fish oil supplements on cancer cachexia and tumor growth.

Authors
Burns, CP; Halabi, S; Clamon, GH; Hars, V; Wagner, BA; Hohl, RJ; Lester, E; Kirshner, JJ; Vinciguerra, V; Paskett, E
MLA Citation
Burns, CP, Halabi, S, Clamon, GH, Hars, V, Wagner, BA, Hohl, RJ, Lester, E, Kirshner, JJ, Vinciguerra, V, and Paskett, E. "Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473." Clin Cancer Res 5.12 (December 1999): 3942-3947.
PMID
10632323
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
5
Issue
12
Publish Date
1999
Start Page
3942
End Page
3947

Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. RESULT: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. CONCLUSION: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.

Authors
Bubley, GJ; Carducci, M; Dahut, W; Dawson, N; Daliani, D; Eisenberger, M; Figg, WD; Freidlin, B; Halabi, S; Hudes, G; Hussain, M; Kaplan, R; Myers, C; Oh, W; Petrylak, DP; Reed, E; Roth, B; Sartor, O; Scher, H; Simons, J; Sinibaldi, V; Small, EJ; Smith, MR; Trump, DL; Wilding, G
MLA Citation
Bubley, GJ, Carducci, M, Dahut, W, Dawson, N, Daliani, D, Eisenberger, M, Figg, WD, Freidlin, B, Halabi, S, Hudes, G, Hussain, M, Kaplan, R, Myers, C, Oh, W, Petrylak, DP, Reed, E, Roth, B, Sartor, O, Scher, H, Simons, J, Sinibaldi, V, Small, EJ, Smith, MR, Trump, DL, and Wilding, G. "Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group." J Clin Oncol 17.11 (November 1999): 3461-3467.
PMID
10550143
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
17
Issue
11
Publish Date
1999
Start Page
3461
End Page
3467
DOI
10.1200/JCO.1999.17.11.3461

A phase II study of docetaxel (Taxotere), estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: preliminary results of cancer and leukemia group B Trial 9780.

Combinations of estramustine with other antimitotic agents, such as docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA), are synergistic in vitro and show significant clinical activity in hormone-refractory prostate cancer (HRPC). We have studied intravenous docetaxel 70 mg/m2, oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. Of the 47 men who were enrolled, 40 are evaluable for response and/or toxicity. One patient (3%) has had a complete response and eight (20%) have had a partial response, yielding a total objective response rate of 23%. Of 39 patients with elevated pretreatment prostate-specific antigen levels who have had at least one posttreatment prostate-specific antigen measurement, 27 (69%) have had > or =50% decreases and 21 (54%) have had > or =75% decreases in prostate-specific antigen levels. Toxicity is modest but manageable. This therapy is efficacious and well tolerated in HRPC and should be compared in phase III trials with other drugs active in HRPC, such as mitoxantrone and hydrocortisone.

Authors
Savarese, D; Taplin, ME; Halabi, S; Hars, V; Kreis, W; Vogelzang, N
MLA Citation
Savarese, D, Taplin, ME, Halabi, S, Hars, V, Kreis, W, and Vogelzang, N. "A phase II study of docetaxel (Taxotere), estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: preliminary results of cancer and leukemia group B Trial 9780." Semin Oncol 26.5 Suppl 17 (October 1999): 39-44.
PMID
10604268
Source
pubmed
Published In
Seminars in Oncology
Volume
26
Issue
5 Suppl 17
Publish Date
1999
Start Page
39
End Page
44

A phase II study of docetaxel (Taxotere), estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: Preliminary results of cancer and leukemia group B trial 9780

Authors
Savarese, D; Taplin, ME; Halabi, S; Hars, V; Kreis, W; Vogelzang, N; Cancer, LGB
MLA Citation
Savarese, D, Taplin, ME, Halabi, S, Hars, V, Kreis, W, Vogelzang, N, and Cancer, LGB. "A phase II study of docetaxel (Taxotere), estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: Preliminary results of cancer and leukemia group B trial 9780." SEMINARS IN ONCOLOGY 26.5 (October 1999): 39-44.
Source
wos-lite
Published In
Seminars in Oncology
Volume
26
Issue
5
Publish Date
1999
Start Page
39
End Page
44

Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study.

PURPOSE: Approximately 40,000 men die each year of hormone-refractory prostate cancer (HRPC). The results of treatment with chemotherapy have been disappointing to date, with no trials demonstrating a benefit with respect to survival duration. Corticosteroids and mitoxantrone each have been shown to be active agents in this disease. The purpose of this study was to demonstrate an advantage of mitoxantrone and hydrocortisone (M+H) over hydrocortisone alone with respect to survival duration. PATIENTS AND METHODS: Two hundred forty-two patients with HRPC were randomized to receive either M+H or hydrocortisone alone. Patients were monitored for survival, time to disease progression, time to treatment failure, response, and quality-of-life (QOL) parameters. RESULTS: Treatment in both arms was well tolerated. Although there was a delay in time to treatment failure and disease progression in favor of M+H over hydrocortisone alone, there was no difference in overall survival (12.3 months for M+H v 12.6 months for hydrocortisone alone). There was an indication that QOL was better with M+H, in particular with respect to pain control. CONCLUSION: M+H generated more frequent responses and a delay in both time to treatment failure and disease progression compared with hydrocortisone alone. In addition, there was a possible benefit of M+H with respect to pain control over hydrocortisone alone. No improvement in survival was observed. Although M+H could be viewed as a palliative option for patients with HRPC, new drugs and novel strategies are needed to improve survival for this disease.

Authors
Kantoff, PW; Halabi, S; Conaway, M; Picus, J; Kirshner, J; Hars, V; Trump, D; Winer, EP; Vogelzang, NJ
MLA Citation
Kantoff, PW, Halabi, S, Conaway, M, Picus, J, Kirshner, J, Hars, V, Trump, D, Winer, EP, and Vogelzang, NJ. "Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study." J Clin Oncol 17.8 (August 1999): 2506-2513.
PMID
10561316
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
17
Issue
8
Publish Date
1999
Start Page
2506
End Page
2513
DOI
10.1200/JCO.1999.17.8.2506

Confusion about mammography: prevalence and consequences.

Over the last decade, there has been significant controversy about the schedule on which women, particularly women in their 40s, should have mammograms. The purpose of the analysis reported here was to assess whether women in their 40s and 50s were confused as a result of the controversy following the January 1997 National Institutes of Health Consensus Development Conference on Breast Cancer Screening For Women Ages 40-49. We also examined if confusion was related to being off schedule for mammography. The study sample included 1287 women recruited from a random sample of 2165 Blue Cross/Blue Shield of North Carolina members. The data described in this analysis were derived from a baseline telephone interview conducted as part of a larger intervention trial. Study measures included a variety of sociodemographic, medical, belief, and behavioral variables. Overall, 28% of women were confused, and 35% were off schedule. Although a higher proportion of women in their 40s than 50s were confused, more women in their 50s were off schedule. Confusion was a significant predictor for the outcome being off schedule. Predictors of confusion included several belief variables, risk perceptions, age (40s), whether the woman had a regular physician, and whether she had enough information about mammography. Healthcare providers should ask some simple questions to determine if women are confused and then seek to meet their information needs.

Authors
Rimer, BK; Halabi, S; Strigo, TS; Crawford, Y; Lipkus, IM
MLA Citation
Rimer, BK, Halabi, S, Strigo, TS, Crawford, Y, and Lipkus, IM. "Confusion about mammography: prevalence and consequences." J Womens Health Gend Based Med 8.4 (May 1999): 509-520.
PMID
10839706
Source
pubmed
Published In
Journal of Women's Health & Gender-Based Medicine
Volume
8
Issue
4
Publish Date
1999
Start Page
509
End Page
520
DOI
10.1089/jwh.1.1999.8.509

p53, c-erbB2, and PCNA status in benign, proliferative and malignant ovarian surface epithelial neoplasms: a study of 75 cases.

Low malignant potential tumors of the ovary are believed to behave in a manner intermediate to their benign and malignant counterparts. However, recent evidence suggests these lesions are in fact benign and better classified as proliferative. Based on our previous work and evaluating p53, c-erbB2, and PCNA status in a full spectrum of ovarian surface epithelial tumors, with emphasis on low malignant potential tumors, we tested this hypothesis. Immunohistochemical stains with monoclonal antibodies were used on 75 archival ovarian neoplasms. The results demonstrated anti-p53 reactivity in 30 carcinomas (40%), 2 of which were proliferative, and no reactivity in the benign tumors. Overexpression of c-erbB2 was seen in 31 malignant neoplasms (64.5%), 4 of which were proliferative (22.1%), and none in benign tumors. The PCNA proliferative index showed means of 42.8%, 22.8%, and 14.9% with benign, low malignant potential, and malignant tumors, respectively. Predicting immunoreactivity in carcinomas for anti-PCNA (Student t test), anti-p53, and anti-c-erbB2 (Pearson chi2 test) versus a lack of immunoreactivity in proliferative tumors indicate P values of .001, <.001, and <.001, respectively. These data show significant differences in the expression of these markers in ovarian tumors and suggest a possible role for these oncogenes as supplemental tools in diagnostic pathology. Further, our findings also support the designation of proliferative as opposed to the current nomenclature of low malignant potential tumors.

Authors
Anreder, MB; Freeman, SM; Merogi, A; Halabi, S; Marrogi, AJ
MLA Citation
Anreder, MB, Freeman, SM, Merogi, A, Halabi, S, and Marrogi, AJ. "p53, c-erbB2, and PCNA status in benign, proliferative and malignant ovarian surface epithelial neoplasms: a study of 75 cases." Arch Pathol Lab Med 123.4 (April 1999): 310-316.
PMID
10320143
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
123
Issue
4
Publish Date
1999
Start Page
310
End Page
316
DOI
10.1043/0003-9985(1999)123<0310:PCEAPS>2.0.CO;2

A phase II study of docetaxel (Taxotere), estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: Preliminary results of cancer and leukemia group B trial 9780

Combinations of estramustine with other antimitotic agents, such as docetaxel (Taxotere; Rhone-Poulenc Rorer, Collegeville, PA), are synergistic in vitro and show significant clinical activity in hormone-refractory prostate cancer (HRPC). We have studied intravenous docetaxel 70 mg/m2, oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. Of the 47 men who were enrolled, 40 are evaluable for response and/or toxicity. One patient (3%) has had a complete response and eight (20%) have had a partial response, yielding a total objective response rate of 23%. Of 39 patients with elevated pretreatment prostate-specific antigen levels who have had at least one posttreatment prostate-specific antigen measurement, 27 (69%) have had ≥50% decreases and 21 (54%) have had ≥75% decreases in prostate-specific antigen levels. Toxicity is modest but manageable. This therapy is efficacious and well tolerated in HRPC and should be compared in phase III trials with other drugs active in HRPC, such as mitoxantrone and hydrocortisone.

Authors
Savarese, D; Taplin, M-E; Halabi, S; Hars, V; Kreis, W; Vogelzang, N
MLA Citation
Savarese, D, Taplin, M-E, Halabi, S, Hars, V, Kreis, W, and Vogelzang, N. "A phase II study of docetaxel (Taxotere), estramustine, and low-dose hydrocortisone in men with hormone-refractory prostate cancer: Preliminary results of cancer and leukemia group B trial 9780." Seminars in Oncology 26.5 SUPPL. 17 (1999): 39-44.
Source
scival
Published In
Seminars in Oncology
Volume
26
Issue
5 SUPPL. 17
Publish Date
1999
Start Page
39
End Page
44

Detection of low level benzene exposure in supermarket wrappers by urinary muconic acid

Women who use the 'hot wire' and 'cool rod' machines to wrap meat in supermarkets are potentially exposed to low levels of benzene and polycyclic aromatic hydrocarbons present in fumes emitted during the thermal decomposition of the plastic used to wrap meat. In order to evaluate whether the benzene metabolite trans, trans-muconic acid (MA) can be used to monitor these low levels, we collected urine samples from supermarket workers, and assayed the urine for MA. Geometric mean after-shift MA levels were highest for subjects who used the 'hot wire' machine, i.e. > 300 ng mg-1 creatinine (Cr). The corresponding levels for subjects who used the 'cool rod' machine were similar to those for subjects who did not use either type of machine, and were much lower. These results indicate that urinary muconic acid has some potential for use in monitoring benzene exposures of less than 1 part per million (ppm). The study detected very high background MA levels (exceeding 2000 ng mg-1 Cr) in some subjects, suggesting that individuals in the general population without occupational exposure to benzene may have urinary MA levels equivalent to exposure to up to 2 ppm benzene in ambient air. However, since non-benzene sources of the metabolite cannot be completely ruled out as partially responsible for these high levels, the public health significance of this finding is not known at the moment.

Authors
Johnson, ES; Halabi, S; Netto, G; Lucier, G; Bechtold, W; Henderson, R
MLA Citation
Johnson, ES, Halabi, S, Netto, G, Lucier, G, Bechtold, W, and Henderson, R. "Detection of low level benzene exposure in supermarket wrappers by urinary muconic acid." Biomarkers 4.2 (1999): 106-117.
Source
scival
Published In
Biomarkers
Volume
4
Issue
2
Publish Date
1999
Start Page
106
End Page
117

Attitudes and knowledge associated with being undecided about hormone replacement therapy: Results from a community sample

Authors
Bastian, LA; McBride, CM; Halabi, S; Fish, LJ; Skinner, CS; Kaplan, EB; Bosworth, HB; Rimer, BK; Siegler, IC
MLA Citation
Bastian, LA, McBride, CM, Halabi, S, Fish, LJ, Skinner, CS, Kaplan, EB, Bosworth, HB, Rimer, BK, and Siegler, IC. "Attitudes and knowledge associated with being undecided about hormone replacement therapy: Results from a community sample." WOMENS HEALTH ISSUES 9.6 (1999): 330-337.
Source
wos-lite
Published In
Women's Health Issues
Volume
9
Issue
6
Publish Date
1999
Start Page
330
End Page
337

Serum androgens: associations with prostate cancer risk and hair patterning.

Authors
Demark-Wahnefried, W; Halabi, S; Paulson, DF
MLA Citation
Demark-Wahnefried, W, Halabi, S, and Paulson, DF. "Serum androgens: associations with prostate cancer risk and hair patterning." J Androl 19.5 (September 1998): 631-. (Letter)
PMID
9796625
Source
pubmed
Published In
Journal of Andrology
Volume
19
Issue
5
Publish Date
1998
Start Page
631

Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: the Washington, DC, Dilated Cardiomyopathy Study.

Although cardiac transplantation offers prolonged survival and improved quality of life to patients with end-stage heart failure, many patients with idiopathic dilated cardiomyopathy do not undergo this procedure. Possible barriers to cardiac transplantation were examined among 138 patients with idiopathic dilated cardiomyopathy from five hospitals in Washington, DC. Patients underwent follow-up for approximately 5 years. The patients or a close family member were interviewed at baseline about socioeconomic factors and medical history. The patients or their next-of-kin were recontacted at 1-year intervals to determine patients' vital status and to obtain information about cardiac transplantation. Overall, the cumulative survival at 12 and 60 months was 75.8% and 37.3%, respectively. Only 3.6% (5 of 138) of the patients underwent cardiac transplantation, and 19 (13.8%) patients had been placed on a waiting list for a heart transplant. Black race and nonmarried status were inversely associated with cardiac transplantation. Factors associated with not having been placed on a waiting list included older age, lower income, and lack of private health insurance. Black race was found to be significantly, but inversely associated with cardiac transplantation while older age was inversely associated with having been placed on a waiting list after adjusting for sex, race, education, and private insurance. These findings suggest that black patients with idiopathic dilated cardiomyopathy are less likely to undergo cardiac transplantation.

Authors
Coughlin, SS; Halabi, S; Metayer, C
MLA Citation
Coughlin, SS, Halabi, S, and Metayer, C. "Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: the Washington, DC, Dilated Cardiomyopathy Study." J Natl Med Assoc 90.6 (June 1998): 342-348.
PMID
9640904
Source
pubmed
Published In
Journal of the National Medical Association
Volume
90
Issue
6
Publish Date
1998
Start Page
342
End Page
348

Letter to the editor

Authors
Demark-Wahnefried, W; Halabi, S; Paulson, DF
MLA Citation
Demark-Wahnefried, W, Halabi, S, and Paulson, DF. "Letter to the editor." Journal of Andrology 19.5 (1998): 631--.
Source
scival
Published In
Journal of Andrology
Volume
19
Issue
5
Publish Date
1998
Start Page
631-

Untitled

Authors
Demark-Wahnefried, W; Halabi, S; Paulson, DF
MLA Citation
Demark-Wahnefried, W, Halabi, S, and Paulson, DF. "Untitled." JOURNAL OF ANDROLOGY 19.5 (1998): 631-631.
Source
wos-lite
Published In
Journal of Andrology
Volume
19
Issue
5
Publish Date
1998
Start Page
631
End Page
631

Relationship between lifetime ovulatory cycles and overexpression of mutant p53 in epithelial ovarian cancer - Response

Authors
Schildkraut, JM; Bastos, E; Halabi, S; Berchuck, A
MLA Citation
Schildkraut, JM, Bastos, E, Halabi, S, and Berchuck, A. "Relationship between lifetime ovulatory cycles and overexpression of mutant p53 in epithelial ovarian cancer - Response." JOURNAL OF THE NATIONAL CANCER INSTITUTE 89.22 (November 19, 1997): 1727-1727.
Source
wos-lite
Published In
Journal of the National Cancer Institute
Volume
89
Issue
22
Publish Date
1997
Start Page
1727
End Page
1727

Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: The Washington, DC dilated cardiomyopathy study

Authors
Coughlin, SS; Halabi, S; Metayer, C
MLA Citation
Coughlin, SS, Halabi, S, and Metayer, C. "Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: The Washington, DC dilated cardiomyopathy study." CIRCULATION 94.8 (October 15, 1996): 4043-4043.
Source
wos-lite
Published In
Circulation
Volume
94
Issue
8
Publish Date
1996
Start Page
4043
End Page
4043

Correlation between selected environmental exposures and karyotype in acute myelocytic leukemia.

Many bone marrow cytogenetic abnormalities in acute myelogenous leukemia (AML) are tumor specific, clonal, nonrandom, and related to prognosis; it has been hypothesized that they may be markers of exposure to etiological agents. A previous report from our institution revealed several such associations; the purpose of the current study was to determine whether previous findings were present in a new group of patients. Subjects included 84 newly diagnosed AML patients (French-American-British M1 and M2); exposure data were gathered using self-report questionnaires at the time of registration. Two sets of comparisons were made: (a) patients with all (AA) or some (AN) cytogenetically abnormal cells versus those with normal karyotypes (NN) and (b) patients with specific abnormalities [-5/5q-, -7/7q-, +8, t(8;21)] versus all others. Odds ratios (ORs) were 4.64 for the association between prior cytotoxic therapy and -5/5q- and 6.38 for the association with -7/7q-, but were <1.00 for +8 and t(8;21). There were no ORs > 2.0 for specific abnormalities in any of the other exposures evaluated (cigarette smoking, alcohol use, occupational exposure to organic chemicals, paints, or pesticides/herbicides), with the exception of exposure to paints and -7/7q- (OR, 7.50). The ORs for AA/AN versus NN patients were 1.43 and 3.81 for smoking and alcohol use, and weak dose-response trends were present. The most consistent positive associations between the two series were for prior cytotoxic therapy (-5/5q-; -7/7q-), cigarette smoking (AA/AN versus NN) and alcohol use (AA/AN versus NN). Reasoning from the known association between prior cytotoxic therapy and -7/7q-, we would have predicted relatively high ORs (> 4.0) if specific abnormalities acted as markers for the exposures assessed, but none were present. However, in both series, AA/AN patients were more likely to smoke and use alcohol than were NN patients, and weak dose-response patterns were present for both. This finding suggests that both smoking and alcohol use may play a role in the pathogenesis of cytogenetic abnormalities in AML-M1/M2; however, the mechanism by which they work and whether they are involved in the etiology of these diseases remain unclear.

Authors
Crane, MM; Strom, SS; Halabi, S; Berman, EL; Fueger, JJ; Spitz, MR; Keating, MJ
MLA Citation
Crane, MM, Strom, SS, Halabi, S, Berman, EL, Fueger, JJ, Spitz, MR, and Keating, MJ. "Correlation between selected environmental exposures and karyotype in acute myelocytic leukemia." Cancer Epidemiol Biomarkers Prev 5.8 (August 1996): 639-644.
PMID
8824367
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
5
Issue
8
Publish Date
1996
Start Page
639
End Page
644

Epirubicin and ifosfamide in metastatic breast cancer.

In a randomized, phase II trial, we evaluated the effectiveness of continued chemotherapy with epirubicin/ ifosfamide versus unmaintained treatment interruption in advanced metastatic breast cancer. Three hundred fifty-seven patients were enrolled and 331 were evaluable for response. Complete response was achieved in 25 patients (8%) and partial response in 121 patients (37%). Pretreatment status correlated significantly with response (complete and partial response). While 54% of unpretreated patients responded, only 42% of the patients responded who had been pretreated with adjuvant chemotherapy and 33% who had been pretreated in the metastatic stage of disease; 69 patients (21%) had disease progression. Of 11 patients pretreated in both the adjuvant and metastatic setting, only two responded. Toxicity of treatment was mild, with leukopenia being the treatment-limiting factor. Thrombocyte levels were not altered significantly by treatment. Thus, there seems to be room for dose escalation using granulocyte colony-stimulating factor. There was no considerable cardiotoxicity, central nervous system toxicity, or cystitis observed. The low rate of cardiotoxicity appeared to be related to dose fractionation of epirubicin. After randomization of patients to treatment interruption versus continuation of chemotherapy, a longer relapse-free survival was observed for patients who continued chemotherapy (mean relapse-free survival, 2+ months); however, this did not translate into prolonged survival. The cumulative scores of toxicity and quality of life parameters showed increasing superiority for treatment interruption. Therefore, a strategy of treatment until maximum response and subsequent treatment interruption seems to be superior to treatment continuation.

Authors
Becher, R; Kloke, O; Hayungs, J; Hartwich, G; Bartels, H; Szanto, J; Wolf, E; Illiger, HJ; Halabi, S; Rieche, K; Hering, KG; Ohl, S; DeDycker, R; Huhn, R; Fischedick, AR; Höfeler, H; Pielken, HJ; Hawig, I; Hirche, H; Seeber, S
MLA Citation
Becher, R, Kloke, O, Hayungs, J, Hartwich, G, Bartels, H, Szanto, J, Wolf, E, Illiger, HJ, Halabi, S, Rieche, K, Hering, KG, Ohl, S, DeDycker, R, Huhn, R, Fischedick, AR, Höfeler, H, Pielken, HJ, Hawig, I, Hirche, H, and Seeber, S. "Epirubicin and ifosfamide in metastatic breast cancer." Semin Oncol 23.3 Suppl 7 (June 1996): 28-33.
PMID
8711499
Source
pubmed
Published In
Seminars in Oncology
Volume
23
Issue
3 Suppl 7
Publish Date
1996
Start Page
28
End Page
33

The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer.

Cervical cancer is the second leading cause of death from cancer in women worldwide, and recent epidemiological studies have strongly implicated the sexually transmitted human papillomavirus (HPV) as a causative agent. The ability of high-risk HPVs to contribute to malignant progression seems to depend on expression of the viral E6 and E7 oncogenes. The E6 oncoprotein forms a complex with the cellular tumor suppressor protein p53, leading to degradation of p53 via ubiquitin-dependent proteolysis. Thus, E6 expression results in the loss of p53 function in cells, including stimulation of apoptosis and inhibition of the expression of the antiapoptotic protein bcl-2. Recently, we found increased bcl-2 expression in cervical carcinoma cell lines containing mutated or E6-inactivated p53 (X. L. Liang, S. Mungal, A. Ayscue, J. D. Meissner, P. Wodnicki, G. Gordon, S. Lockett, and B. Herman. J. Cell. Biochem., 57: 509-520, 1995). Based on these findings, we examined Papanicolaou smears from 94 women with varying degrees of cervical disease for the presence or absence of p53, HPV-16/18 E6, and bcl-2 proteins using immunofluorescence microscopy. Our findings indicate that there is a statistically significant, inverse association between the presence of p53 and invasive cervical disease [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7]. Moreover, the odds of being diagnosed with an invasive stage of cervical cancer were 3.7 times higher (95% CI, 1.6-8.8) for women positive for the E6 protein and 17 times higher (95% CI, 5.5-58.3) for women positive for the bcl-2 protein compared with women negative for E6 and bcl-2. Women with invasive cervical cancer were also 4.59 times more likely to test positive for the presence of more than one marker (95% CI, 1.8-11.8). Chi(2) analysis demonstrated a strong association between the presence of E6 and bcl-2 (P < 0.001) as well as between the presence of E6 of bcl-2 and diagnosis (P = 0.015 and < 0.001, respectively). In the multivariate analysis, the presence of bcl-2 (OR, 18.8; 95% CI, 5.5-67.8) and age at diagnosis (> or = 50 years; OR, 7.8; 95% CI, 2.5-24.5) showed significant association with Invasive cervical disease. These findings indicate that: (a) the presence of the bcl-2 protein is strongly associated with the development of invasive cervical disease: (b) the pattern of the presence of high-risk HPV-E6, p53, and bcl-2 proteins may be useful for identifying women at increased risk for the development of invasive cervical cancer; and (c) a defect in apoptosis may partially underlie the development of cervical cancer.

Authors
Pillai, MR; Halabi, S; McKalip, A; Jayaprakash, PG; Rajalekshmi, TN; Nair, MK; Herman, B
MLA Citation
Pillai, MR, Halabi, S, McKalip, A, Jayaprakash, PG, Rajalekshmi, TN, Nair, MK, and Herman, B. "The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer." Cancer Epidemiol Biomarkers Prev 5.5 (May 1996): 329-335.
PMID
9162297
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
5
Issue
5
Publish Date
1996
Start Page
329
End Page
335

Oncogene profile in pre versus postmenopausal women with breast carcinoma: Evidence of different p53 mutation patterns

Authors
Munshi, A; Marrogi, OL; Halabi, S; Merogi, AI; Freeman, SM; Marrogi, AI
MLA Citation
Munshi, A, Marrogi, OL, Halabi, S, Merogi, AI, Freeman, SM, and Marrogi, AI. "Oncogene profile in pre versus postmenopausal women with breast carcinoma: Evidence of different p53 mutation patterns." FASEB JOURNAL 10.6 (April 30, 1996): 839-839.
Source
wos-lite
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
10
Issue
6
Publish Date
1996
Start Page
839
End Page
839

Automated image microscopy

Authors
Wodnicki, P; Lockett, S; Pillai, MR; Halabi, S; McKalip, A; Herman, B
MLA Citation
Wodnicki, P, Lockett, S, Pillai, MR, Halabi, S, McKalip, A, and Herman, B. "Automated image microscopy." Chemical Analysis 137 (1996): 31-54.
Source
scival
Published In
Chemical Analysis : a Series of Monographs on Analytical Chemistry and Its Applications
Volume
137
Publish Date
1996
Start Page
31
End Page
54

Epirubicin and ifosfamide in metastatic breast cancer

In a randomized, phase II trial, we evaluated the effectiveness of continued chemotherapy with epirubicin/ifosfamide versus unmaintained treatment interruption in advanced metastatic breast cancer. Three hundred fifty-seven patients were enrolled and 331 were evaluable for response. Complete response was achieved in 25 patients (8%) and partial response in 121 patients (37%). Pretreatment status correlated significantly with response (complete and partial response). While 54% of unpretreated patients responded, only 42% of the patients responded who had been pretreated with adjuvant chemotherapy and 33% who had been pretreated in the metastatic stage of disease; 69 patients (21%) had disease progression. Of 11 patients pretreated in both the adjuvant and metastatic setting, only two responded. Toxicity of treatment was mild, with leukopenia being the treatment-limiting factor. Thrombocyte levels were not altered significantly by treatment. Thus, there seems to be room for dose escalation using granulocyte colony- stimulating factor. There was no considerable cardiotoxicity, central nervous system toxicity, or cystitis observed. The low rate of cardiotoxicity appeared to be related to dose fractionation of epirubicin. After randomization of patients to treatment interruption versus continuation of chemotherapy, a longer relapse-free survival was observed for patients who continued chemotherapy (mean relapse-free survival, 2+ months); however, this did not translate into prolonged survival. The cumulative scores of toxicity and quality of life parameters showed increasing superiority for treatment interruption. Therefore, a strategy of treatment until maximum response and subsequent treatment interruption seems to be superior to treatment continuation.

Authors
Becher, R; Kloke, O; Hayungs, J; Hartwich, G; Bartels, H; Szanto, J; Wolf, E; Illiger, H-J; Halabi, S; Rieche, K; Hering, KG; Ohl, S; DeDycker, R; Huhn, R; Fischedick, A-R; Hofeler, H; Pielken, HJ; Hawig, I; Hirche, H; Seeber, S
MLA Citation
Becher, R, Kloke, O, Hayungs, J, Hartwich, G, Bartels, H, Szanto, J, Wolf, E, Illiger, H-J, Halabi, S, Rieche, K, Hering, KG, Ohl, S, DeDycker, R, Huhn, R, Fischedick, A-R, Hofeler, H, Pielken, HJ, Hawig, I, Hirche, H, and Seeber, S. "Epirubicin and ifosfamide in metastatic breast cancer." Seminars in Oncology 23.3 SUPPL. 7 (1996): 28-33.
Source
scival
Published In
Seminars in Oncology
Volume
23
Issue
3 SUPPL. 7
Publish Date
1996
Start Page
28
End Page
33

Frequent detection of bcl-2/JH translocations in human blood and organ samples by a quantitative polymerase chain reaction assay.

Using an ultrasensitive assay involving the PCR, we have examined the frequency of a follicular lymphoma-associated translocation in peripheral blood from 132 individuals, most of whom were healthy blood donors. This translocation occurs between the bcl-2 proto-oncogene and the JH gene region and prolongs the life of lymphocytes. At a level of sensitivity of 1 translocation-bearing cell per 5 x 10(6) cells, almost one-half of healthy human adults had this translocation in the mononuclear fraction of peripheral blood. However, the range of frequency of these translocations spanned almost three orders of magnitude among translocation-positive individuals. Furthermore, there was a statistically significant increase with age in the percentage of individuals who were translocation positive. Such an age correlation was also seen for the percentage of blood donors with rather high translocation frequencies (> or = 20 per 5 x 10(6) peripheral blood mononuclear cells). However, the blood donor who had by far the highest concentration of this translocation was a healthy 35-year-old male containing approximately 900 apparently monoclonal, translocation-bearing cells per 5 x 10(6) peripheral blood mononuclear cells. Our findings suggest that some individuals who may be at risk for follicular lymphoma might be able to be identified by this PCR assay on peripheral blood. Also, these data may help explain the age dependence of the occurrence of this cancer.

Authors
Ji, W; Qu, GZ; Ye, P; Zhang, XY; Halabi, S; Ehrlich, M
MLA Citation
Ji, W, Qu, GZ, Ye, P, Zhang, XY, Halabi, S, and Ehrlich, M. "Frequent detection of bcl-2/JH translocations in human blood and organ samples by a quantitative polymerase chain reaction assay." Cancer Res 55.13 (July 1, 1995): 2876-2882.
PMID
7796416
Source
pubmed
Published In
Cancer Research
Volume
55
Issue
13
Publish Date
1995
Start Page
2876
End Page
2882

Validation of a breast cancer risk assessment model in women with a positive family history.

BACKGROUND: Gail et al. developed a statistical model for estimating the risk of developing breast cancer in white women screened annually with mammography. This model is used for counseling and for admission to clinical trials. PURPOSE: We evaluated the model prospectively in a cohort of women with a family history of breast cancer. METHODS: We followed women who participated in the American Cancer Society 1987 Texas Breast Screening Project. The model was evaluated by comparing the observed (O) and expected (E) numbers of breast cancers using composite background rates from both the Breast Cancer Detection and Demonstration Project and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Data were partitioned by adherence to American Cancer Society screening guidelines. RESULTS: The Gail et al. model predicted the risk well among women who adhered to the American Cancer Society guidelines (O/E = 1.12; 95% confidence interval = 0.75-1.61) but overpredicted risk for women who did not adhere to the guidelines. There was an indication that the model overpredicted risk for women younger than 60 years old and underpredicted risk in women aged 60 years and older. CONCLUSIONS: Overall, the Gail et al. model accurately predicts risk in women with a family history of breast cancer and who adhere to American Cancer Society screening guidelines. Thus, the model should be used as it was intended, for women who receive annual mammograms.

Authors
Bondy, ML; Lustbader, ED; Halabi, S; Ross, E; Vogel, VG
MLA Citation
Bondy, ML, Lustbader, ED, Halabi, S, Ross, E, and Vogel, VG. "Validation of a breast cancer risk assessment model in women with a positive family history." J Natl Cancer Inst 86.8 (April 20, 1994): 620-625.
PMID
8003106
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
86
Issue
8
Publish Date
1994
Start Page
620
End Page
625

Factors associated with perceived risk of breast cancer among women attending a screening program.

A person's perception of the risk of, or susceptibility to, developing a disease is believed to be an important determinant of health-related behavior, yet little is known about the determinants of perceived risk. Knowledge of these correlates may be useful in identifying and addressing barriers to performance of health behaviors such as mammography screening. Data collected from over 36,000 women participating in a breast cancer screening program in Texas were used to examine the associations between perceived risk of ever getting breast cancer and a number of demographic factors, health-related behaviors, and risk factors for breast cancer. There was a strong positive association between family history of breast cancer and risk perception (OR = 11.3, CI = 10.34-12.35). Women who reported other risk factors for breast cancer also reported higher perceived risk, but those associations were of lesser magnitude. Age was inversely associated with perceived risk, and black, but not Hispanic, women were more likely to perceive their risk as high compared with white women. Of the health-related behaviors for the early detection of breast cancer, only having had a prior mammogram was associated with perceived risk. Educational interventions to heighten women's awareness of breast cancer risk factors may increase perceived risk in high risk women and influence their decision to undergo screening mammography.

Authors
Vernon, SW; Vogel, VG; Halabi, S; Bondy, ML
MLA Citation
Vernon, SW, Vogel, VG, Halabi, S, and Bondy, ML. "Factors associated with perceived risk of breast cancer among women attending a screening program." Breast Cancer Res Treat 28.2 (November 1993): 137-144.
PMID
8173066
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
28
Issue
2
Publish Date
1993
Start Page
137
End Page
144

Mutagen sensitivity in upper aerodigestive tract cancer: a case-control analysis.

Variability in DNA repair capability may be a determinant of interindividual difference in susceptibility to carcinogenic exposures. A cytogenetic assay which quantifies chromosomal breakage induced by in vitro exposure to a clastogen provides an indirect measure of repair. We report the results of a case-control study of upper aerodigestive tract cancers assessing differences in mutagen sensitivity based on this assay. There were 108 cases with previously untreated squamous cell cancers and 108 age and sex frequency-matched controls selected from blood donors to The University of Texas M. D. Anderson Cancer Center. Sixty-nine% of the cases, compared with 44% of the controls, were classified as mutagen sensitive (breaks per cell > or = 0.8). On multivariate analysis, mutagen sensitivity [odds ratio (OR), 2.5], heavy cigarette smoking (OR, 4.8), and heavy alcohol consumption (OR, 3.1) were associated with significantly increased risk. Stratified analyses showed that the combined effects of cigarette smoking (OR, 8.1) and mutagen sensitivity (OR, 3.2) were suggestive of a multiplicative effect (OR, 23.0). The combined estimate for alcohol use (OR, 3.0) and mutagen sensitivity (OR, 3.0) was 5.8. These data confirm those of a previously published preliminary study of upper aerodigestive cancers and underscore the importance of considering interindividual susceptibility in cancer risk characterization, even for those cancers with well quantified exposures.

Authors
Spitz, MR; Fueger, JJ; Halabi, S; Schantz, SP; Sample, D; Hsu, TC
MLA Citation
Spitz, MR, Fueger, JJ, Halabi, S, Schantz, SP, Sample, D, and Hsu, TC. "Mutagen sensitivity in upper aerodigestive tract cancer: a case-control analysis." Cancer Epidemiol Biomarkers Prev 2.4 (July 1993): 329-333.
PMID
7688625
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
2
Issue
4
Publish Date
1993
Start Page
329
End Page
333

Incidence of autoimmune disease in patients after breast reconstruction with silicone gel implants versus autogenous tissue: a preliminary report.

OBJECTIVE: To test the hypothesis that there is a higher incidence of autoimmune disorders in patients who have undergone breast reconstruction with silicone gel implants rather than autogenous tissue. DESIGN: Prospective study. SETTING: Tertiary referral center dealing exclusively with cancer. PATIENTS: All female breast cancer patients who underwent breast reconstruction between January 1986 and March 1992. Patients were nonrandomly assigned to breast reconstruction with one of the following four methods: (1) silicone gel implant only, (2) latissimus dorsi flap with implant, (3) latissimus dorsi flap without implant, and (4) transverse rectus abdominis flap. The first two groups made up the implant cohort and the last two groups the autogenous tissue cohort. Selection of reconstructive method was made on clinical grounds and was based on both physician and patient preference. MAIN OUTCOME MEASURES: Documented diagnosis of autoimmune disorder by Board-certified rheumatologist. RESULTS: Three hundred eight implants were used in 250 patients, and 408 reconstructions with tissue were performed on 353 patients. The two groups were similar in age and tumor stage. The two groups contributed 615.8 and 663.4 person-years of follow-up, respectively. One patient from each group (< 0.5%) had a documented occurrence of an autoimmune syndrome requiring therapy. Both cases were considered mild, and after initial low-dose steroid therapy, both patients are now off steroids. CONCLUSION: The incidence of autoimmune disease in mastectomy patients receiving silicone gel implants is not different than in patients who had reconstruction with autogenous tissue.

Authors
Schusterman, MA; Kroll, SS; Reece, GP; Miller, MJ; Ainslie, N; Halabi, S; Balch, CM
MLA Citation
Schusterman, MA, Kroll, SS, Reece, GP, Miller, MJ, Ainslie, N, Halabi, S, and Balch, CM. "Incidence of autoimmune disease in patients after breast reconstruction with silicone gel implants versus autogenous tissue: a preliminary report." Ann Plast Surg 31.1 (July 1993): 1-6.
PMID
8395164
Source
pubmed
Published In
Annals of Plastic Surgery
Volume
31
Issue
1
Publish Date
1993
Start Page
1
End Page
6

The Texas Breast Screening Project: Part I. Mammographic and clinical results.

The 1987 Texas Breast Screening Project was designed to educate women about the benefits and safety of mammographic screening. During the 2-week promotion, 109,339 women called toll-free telephone numbers to inquire about the program, and 64,459 (65%) of 99,650 eligible callers had $50 mammograms at 306 participating community radiology centers. Biopsies were obtained for 1,122 women (1.7% of those screened), and the ratio of benign to malignant biopsy results was 4.2:1. Among the women having biopsies, 214 cancers were found (3.3 cancers per 1,000 women screened). Forty-seven percent of the tumors were not palpable, 80% were smaller than 2 cm, and 72% were clinicopathologic stage 0 or I. These results show that women will respond to an invitation to attend mammographic screening, and that community radiology centers can detect large numbers of early, curable breast cancers.

Authors
Peters, GN; Vogel, VG; Evans, WP; Bondy, M; Halabi, S; Lord, J; Laville, EA
MLA Citation
Peters, GN, Vogel, VG, Evans, WP, Bondy, M, Halabi, S, Lord, J, and Laville, EA. "The Texas Breast Screening Project: Part I. Mammographic and clinical results." South Med J 86.4 (April 1993): 385-390.
PMID
8465213
Source
pubmed
Published In
Southern Medical Journal
Volume
86
Issue
4
Publish Date
1993
Start Page
385
End Page
390

The Texas Breast Screening Project: Part II. Demographics, risk profiles, and health practices of participants.

More than 36,000 of the 64,459 women who had $50 mammograms after a media campaign in 1987 completed a demographic and risk factor questionnaire. The screened women were young and well educated with high annual incomes. Only 32% had had mammograms before 1987. Most women reported that high cost and lack of referral for mammography by their physicians were their reasons for not being screened previously. Publicity promoting the project and the lower cost for mammography were the features of the project that attracted participants. Population-based telephone surveys before and after the project showed a change in attitudes about breast cancer screening. The model used for recruitment in this project can improve compliance with recommendations for regular mammographic screening if charges for screening are reduced. Additional efforts are needed to attract minorities and poor or elderly women to regular breast screening.

Authors
Vogel, VG; Bondy, M; Halabi, S; Lord, J; Laville, EA
MLA Citation
Vogel, VG, Bondy, M, Halabi, S, Lord, J, and Laville, EA. "The Texas Breast Screening Project: Part II. Demographics, risk profiles, and health practices of participants." South Med J 86.4 (April 1993): 391-396.
PMID
8465214
Source
pubmed
Published In
Southern Medical Journal
Volume
86
Issue
4
Publish Date
1993
Start Page
391
End Page
396

Association between family history of cancer and mutagen sensitivity in upper aerodigestive tract cancer patients.

This study evaluated the relationship between family history of cancer and bleomycin-induced mutagen sensitivity. The study included 108 patients who registered at The University of Texas M.D. Anderson Cancer Center from June 1987 to June 1991 with histologically confirmed and previously untreated squamous cell carcinoma of the upper aerodigestive tract. All patients underwent the mutagen sensitivity assay and completed a self-administered risk evaluation questionnaire, including a detailed family history. The patients reported having 650 first-degree relatives, including 54 cases with cancers. The patients were classified as mutagen sensitive (> or = 1 chromosome break/cell) or not mutagen sensitive (< or = 0.99 chromosome breaks/cell). Odds ratios (ORs) were calculated to test for significant associations between mutagen sensitivity and family history of cancer. We found a significant OR (OR = 2.63; 95% confidence interval = 1.06-6.53) for patients who were mutagen sensitive and had one first-degree relative affected with cancer. For mutagen-sensitive patients with two or more first-degree relatives affected with cancer, the OR increased to 6.59 (95% confidence interval = 1.69-25.72). Although 88% of the patients were ever smokers, cigarette smoking was not found to be related to mutagen sensitivity. The study findings suggest that patients who have defective DNA repair capability as evidenced by the mutagen sensitivity assay are significantly more likely to report a family history of cancer than patients who are not mutagen sensitive. Further studies are needed to confirm that mutagen-sensitive individuals have inherited an increased risk of cancer.

Authors
Bondy, ML; Spitz, MR; Halabi, S; Fueger, JJ; Schantz, SP; Sample, D; Hsu, TC
MLA Citation
Bondy, ML, Spitz, MR, Halabi, S, Fueger, JJ, Schantz, SP, Sample, D, and Hsu, TC. "Association between family history of cancer and mutagen sensitivity in upper aerodigestive tract cancer patients." Cancer Epidemiol Biomarkers Prev 2.2 (March 1993): 103-106.
PMID
7682127
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
2
Issue
2
Publish Date
1993
Start Page
103
End Page
106

Recruiting older women for screening mammography.

We compared health behavior and attitudes of older and younger women toward breast cancer screening by using data from the 1987 Texas Breast Screening Project, a community-based, low-cost screening program sponsored by the American Cancer Society, Texas Division. Because age is an important risk factor for breast cancer, the women were categorized into three age groups: 55 to 64 years old, 65 to 74 years old, and 75 years and older. Approximately 67% of the women 75 years and older, 64% of women in the 65 to 74 age group, and 59% of the younger (55 to 64) women had never had mammography. Moreover, only 14% of the women in both the 65 to 74 and 75+ age groups and 19% of the younger women reported having two or more mammographic examinations. Fewer older women (65 to 74 and 75+ age groups) reported having recent clinical breast examination. There were no differences among the age groups in the factors that attracted the women to participate in this screening program; in the three age groups, the most influential factors to participate were media publicity and lower mammography costs. Women in all age groups reported a lack of physician referral and cost as reasons for not previously participating in mammography screening. This study shows that older women are underscreened. Educational programs about the benefits of early detection should target older women because they are at increased risk for breast cancer.

Authors
Halabi, S; Vogel, VG; Bondy, ML; Vernon, SW
MLA Citation
Halabi, S, Vogel, VG, Bondy, ML, and Vernon, SW. "Recruiting older women for screening mammography." Cancer Detect Prev 17.3 (1993): 359-365.
PMID
8402722
Source
pubmed
Published In
Cancer Detection and Prevention
Volume
17
Issue
3
Publish Date
1993
Start Page
359
End Page
365

Low incidence of familial breast cancer among Hispanic women.

There is a paucity of data on familial patterns of breast cancer among minority populations. This study compared the frequency of cancer in 1,095 first-degree relatives of 50 White, 46 Black, and 49 Hispanic breast-cancer patients referred to The University of Texas M.D. Anderson Cancer Center (United States). Family histories of cancer were derived from a self-administered questionnaire on risk factors. Expected numbers of cancers were calculated from the Connecticut Tumor Registry for White and Black relatives and from the New Mexico Tumor Registry for Hispanic relatives. Family history of a first-degree relative with breast cancer was the most important risk factor for both Black and White patients. Significantly elevated standardized incidence ratios (SIR) for breast cancer were noted among White (SIR = 4.5, 95 percent confidence interval [CI] = 1.2-11.4) and Black (SIR = 4.1, CI = 1.1-10.4) relatives younger than age 45. Despite the small number of Black patients, the combined effect of family history of breast cancer and the relative's age at diagnosis (under 45 years) was associated with an SIR of 7.1 (CI = 1.9-18.1). A deficit of cancer was noted in Hispanic women; only one patient reported having a first-degree relative with breast cancer. These findings, although based on small numbers, suggest that Hispanics have a lower rate of familial breast cancer than Whites and Blacks, and that they may possess protective factors that reduce their risk for breast cancer.

Authors
Bondy, ML; Spitz, MR; Halabi, S; Fueger, JJ; Vogel, VG
MLA Citation
Bondy, ML, Spitz, MR, Halabi, S, Fueger, JJ, and Vogel, VG. "Low incidence of familial breast cancer among Hispanic women." Cancer Causes Control 3.4 (July 1992): 377-382.
PMID
1617126
Source
pubmed
Published In
Cancer Causes & Control
Volume
3
Issue
4
Publish Date
1992
Start Page
377
End Page
382

Reliability and validity of self and proxy reporting of morbidity data: a case study from Beirut, Lebanon.

We compared the self-reported illnesses (heart disease, back pain, rheumatoid arthritis, hypertension, and pulmonary disease) and smoking histories of 100 cases and 100 controls matched for age and sex with reports of this information from proxy informants from the same household in two areas in the city of Beirut. In addition, both cases and controls were given physical examinations to evaluate the accuracy of the responses. The level of agreement between the responses of subjects and of their informants varied from one condition to the other. Heart disease had the highest level of agreement, with the proportion of agreement greater than 93% for the cases and the controls and having chi values of 0.79 and 1.0, respectively. The report of back pain exhibited the lowest level of agreement, with responses showing a proportion of agreement of 74% for the cases and 90% for the controls, with chi values of 0.49 and 0.50, respectively. In comparing the responses of subjects and proxy informants with the results of physical examinations, heart disease had the highest level of agreement (J index ranged from 0.69 to 0.84), and back pain had the lowest level of agreement (J index ranged 0.42 to 0.48). These results show that proxy informants are good respondents for members of the same household and that health interview surveys are accurate for data collection of well defined chronic conditions.

Authors
Halabi, S; Zurayk, H; Awaida, R; Darwish, M; Saab, B
MLA Citation
Halabi, S, Zurayk, H, Awaida, R, Darwish, M, and Saab, B. "Reliability and validity of self and proxy reporting of morbidity data: a case study from Beirut, Lebanon." Int J Epidemiol 21.3 (June 1992): 607-612.
PMID
1386064
Source
pubmed
Published In
International Journal of Epidemiology
Volume
21
Issue
3
Publish Date
1992
Start Page
607
End Page
612

Breast cancer screening behaviors and attitudes in three racial/ethnic groups.

Data from a multiethnic sample of women participating in the American Cancer Society 1987 Texas Breast Screening Project was used to compare attitudes and behaviors related to breast cancer screening for whites, blacks, and Hispanics. In general, similar patterns of association were observed across racial/ethnic groups between a number of demographic and risk factors and prior mammography and recent clinical breast examination (CBE), although the magnitude of the associations varied somewhat across groups. Reasons for not having had prior mammography also were similar across groups, with lack of physician referral and cost cited as the two most important reasons. However, Hispanics were less likely than blacks or whites to report prior breast cancer screening, including mammography, CBE, and breast self-examination (BSE). This study demonstrated that women of different racial/ethnic backgrounds can be successfully recruited to participate in a patient-initiated, community-based program. However, this programmatic approach requires augmentation with other intervention strategies designed to reach low-income women because women with more years of education and higher family income were overrepresented in all three groups.

Authors
Vernon, SW; Vogel, VG; Halabi, S; Jackson, GL; Lundy, RO; Peters, GN
MLA Citation
Vernon, SW, Vogel, VG, Halabi, S, Jackson, GL, Lundy, RO, and Peters, GN. "Breast cancer screening behaviors and attitudes in three racial/ethnic groups." Cancer 69.1 (January 1, 1992): 165-174.
PMID
1727659
Source
pubmed
Published In
Cancer
Volume
69
Issue
1
Publish Date
1992
Start Page
165
End Page
174

Identification of women at increased risk for breast cancer in a population-based screening program.

A multivariate model to assess breast cancer risk was developed by Gail et al. (M. H. Gail, L. A. Brinton, D. B. Byar, D. K. Corle, S. B. Green, C. Schairer, and J. J. Mulvihill, J. Natl. Cancer Inst., 81: 1879-1886, 1989) based on data analysis of the Breast Cancer Detection and Demonstration Project. We evaluated the model's usefulness for assigning women to risk groups for counseling and follow-up by applying it to the 1987 Texas Breast Screening Project data. We identified 3165 women with one or more first-degree relatives affected with breast cancer. The mean risk score for the group was 3.3 (range, 2.7-11.8), indicating a greater than 3-fold elevated risk. The mean risk score for the remaining 27,439 women without affected first-degree relatives was 1.5 (range, 1.24-3.2). Risk perception was found to be a motivator for participation. Women with a risk score greater than 5 perceived themselves to be at high risk for breast cancer. The perception of risk was related to the type of affected first-degree relatives: 80.0% of the women with three affected first-degree relatives and 71.5% of women whose mother and sister were both affected with breast cancer perceived themselves to be at high risk. The Gail model is potentially useful in the clinical setting because women at high risk for breast cancer can be entered into etiological studies, enrolled in primary prevention trials, or referred to programs seeking to improve compliance with screening mammography. The Gail model needs validation, but it is useful for estimating the risk of breast cancer in large populations.

Authors
Bondy, ML; Vogel, VG; Halabi, S; Lustbader, ED
MLA Citation
Bondy, ML, Vogel, VG, Halabi, S, and Lustbader, ED. "Identification of women at increased risk for breast cancer in a population-based screening program." Cancer Epidemiol Biomarkers Prev 1.2 (January 1992): 143-147.
PMID
1306097
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
1
Issue
2
Publish Date
1992
Start Page
143
End Page
147

Epidemiology of primary health problems in Beirut

As a result of 12 years of civil war in Lebanon, it has been impossible to collect regular morbidity information at the primary level. This report is based on a case-control analysis of various health problems as identified from a population based health survey in Beirut in 1983-1984. Cases of headache, backpain and peptic ulcer, as identified from this survey of 2752 households, were matched for age, sex, and neighbourhood with controls from the same sample. Cases and controls were compared for the presence of various characteristics as collected in the household interview. Headaches were more prevalent in females and in the higher educational categories, and the odds ratio was 1.3 (95 per cent confidence interval 1.01-1.68) for the married compared to the non-married. In comparisons of backpain, the odds ratio for alcohol consumption was 2.40 (1.14-5.08), and for belonging to skilled and unskilled labour categories of occupation it was 2.33 (1.05-5.15) when the analysis was limited to the employed group only. Although the peptic ulcer cases were of lower educational background compared to their controls, no other findings were identified in this third case-control comparison. The methodological shortcomings of such studies and the various interpretations of the findings are presented in the discussion.

Authors
Armenian, HK; Halabi, SS; Khlat, M
MLA Citation
Armenian, HK, Halabi, SS, and Khlat, M. "Epidemiology of primary health problems in Beirut." Journal of Epidemiology and Community Health 43.4 (1989): 315-318.
PMID
2533238
Source
scival
Published In
Journal of Epidemiology and Community Health
Volume
43
Issue
4
Publish Date
1989
Start Page
315
End Page
318

Hospital visitors as controls

Authors
Armenian, HK; Lakkis, NG; Sibai, AM; Halabi, SS
MLA Citation
Armenian, HK, Lakkis, NG, Sibai, AM, and Halabi, SS. "Hospital visitors as controls." American Journal of Epidemiology 127.2 (1988): 404-406.
PMID
3337090
Source
scival
Published In
American Journal of Epidemiology
Volume
127
Issue
2
Publish Date
1988
Start Page
404
End Page
406

Measures of social class based on education for use in health studies in developing countries.

In this paper we consider the appropriateness of education, compared to occupation and income, as a measure of social class for use in health-related studies in developing societies in transition. Three evaluation criteria were used, namely, the feasibility of constructing the measure, its sensitivity in reflecting relevant social class life conditions, and its ability to produce a family-level measure of social class. We used two data sets from community health surveys in areas of Amman city, Jordan, and in Beirut city, Lebanon, to define a family-based average educational score. We then proceeded, using the Beirut data, to test the score's ability to discriminate social class effects on family health, compared to a more standard representation based on the educational level of the head of the family. It was found that the performance of the average educational score was often better than, but not consistently superior to, the educational level of the head of the family.

Authors
Zurayk, H; Halabi, S; Deeb, M
MLA Citation
Zurayk, H, Halabi, S, and Deeb, M. "Measures of social class based on education for use in health studies in developing countries." J Epidemiol Community Health 41.2 (June 1987): 173-179.
PMID
3309117
Source
pubmed
Published In
Journal of Epidemiology and Community Health
Volume
41
Issue
2
Publish Date
1987
Start Page
173
End Page
179

Modernization and consanguineous marriage in Beirut.

Authors
Khlat, M; Halabi, S
MLA Citation
Khlat, M, and Halabi, S. "Modernization and consanguineous marriage in Beirut." J Biosoc Sci 18.4 (October 1986): 489-495.
PMID
3782199
Source
pubmed
Published In
Journal of Biosocial Science
Volume
18
Issue
4
Publish Date
1986
Start Page
489
End Page
495

Perception of consanguineous marriages and their genetic effects among a sample of couples from Beirut.

We interviewed 100 women who had married a relative and 100 other women of the same age, religious affiliation, and socioeconomic status, but who were not related to their husbands. Both women were selected from a hospital setting in Beirut, and were questioned about their outlook on consanguineous marriages, their awareness of the genetic consequences of consanguinity, and their relationships with in-laws. In general, the women in consanguineous marriages were more favorably inclined than the matched women to marriages between relatives; however, about half of each group would advise their son/daughter to marry his/her cousin. Awareness of the genetic consequences of consanguinity was wide-spread among the respondents, although the women who had married a relative were reluctant to express it. These women also reported better relationships with in-laws, which may be considered as a social benefit derived from consanguineous marriages. Based on the above findings, recommendations are made regarding the content of a public health educational program.

Authors
Khlat, M; Halabi, S; Khudr, A; Der Kaloustian, VM
MLA Citation
Khlat, M, Halabi, S, Khudr, A, and Der Kaloustian, VM. "Perception of consanguineous marriages and their genetic effects among a sample of couples from Beirut." Am J Med Genet 25.2 (October 1986): 299-306.
PMID
3777026
Source
pubmed
Published In
American Journal of Medical Genetics Part A
Volume
25
Issue
2
Publish Date
1986
Start Page
299
End Page
306
DOI
10.1002/ajmg.1320250215

Estimating historical atmospheric mercury concentrations from silver mining and their legacies in present-day surface soil in Potosí, Bolivia

Detailed Spanish records of mercury use and silver production during the colonial period in Potosí, Bolivia were evaluated to estimate atmospheric emissions of mercury from silver smelting. Mercury was used in the silver production process in Potosí and nearly 32,000 metric tons of mercury were released to the environment. AERMOD was used in combination with the estimated emissions to approximate historical air concentrations of mercury from colonial mining operations during 1715, a year of relatively low silver production. Source characteristics were selected from archival documents, colonial maps and images of silver smelters in Potosí and a base case of input parameters was selected. Input parameters were varied to understand the sensitivity of the model to each parameter. Modeled maximum 1-h concentrations were most sensitive to stack height and diameter, whereas an index of community exposure was relatively insensitive to uncertainty in input parameters. Modeled 1-h and long-term concentrations were compared to inhalation reference values for elemental mercury vapor. Estimated 1-h maximum concentrations within 500 m of the silver smelters consistently exceeded present-day occupational inhalation reference values. Additionally, the entire community was estimated to have been exposed to levels of mercury vapor that exceed present-day acute inhalation reference values for the general public. Estimated long-term maximum concentrations of mercury were predicted to substantially exceed the EPA Reference Concentration for areas within 600 m of the silver smelters. A concentration gradient predicted by AERMOD was used to select soil sampling locations along transects in Potosí. Total mercury in soils ranged from 0.105 to 155 mg kg-1, among the highest levels reported for surface soils in the scientific literature. The correlation between estimated air concentrations and measured soil concentrations will guide future research to determine the extent to which the current community of Potosí and vicinity is at risk of adverse health effects from historical mercury contamination. © 2010 Elsevier Ltd.

Authors
Hagan, N; Robins, N; Hsu-Kim, H; Halabi, S; Morris, M; Woodall, G; Zhang, T; Bacon, A; Richter, DDB; Vandenberg, J
MLA Citation
Hagan, N, Robins, N, Hsu-Kim, H, Halabi, S, Morris, M, Woodall, G, Zhang, T, Bacon, A, Richter, DDB, and Vandenberg, J. "Estimating historical atmospheric mercury concentrations from silver mining and their legacies in present-day surface soil in Potosí, Bolivia." Atmospheric Environment.
Source
scival
Published In
Atmospheric Environment
DOI
10.1016/j.atmosenv.2010.10.009
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Research Areas:

  • Adenocarcinoma
  • Adenocarcinoma, Clear Cell
  • African Americans
  • Age Factors
  • Aged, 80 and over
  • Alkaline Phosphatase
  • Alleles
  • Arab countries
  • Area Under Curve
  • Biological Markers
  • Biomarkers, Pharmacological
  • Breast Neoplasms
  • Cancer Vaccines
  • Carcinoma
  • Carcinoma, Renal Cell
  • Case-Control Studies
  • Chemoprevention
  • Chemotherapy
  • Chi-Square Distribution
  • Cities
  • Clinical Trials, Phase II as Topic
  • Clinical trials
  • Cohort Studies
  • Computer Simulation
  • Confidence Intervals
  • Construction Materials
  • Contraceptives, Oral
  • DNA Damage
  • DNA Primers
  • DNA Repair
  • DNA, Neoplasm
  • Data Interpretation, Statistical
  • Decision Making
  • Decision Support Techniques
  • Diagnostic Imaging
  • Disease Progression
  • Disease-Free Survival
  • Drug Design
  • Dust
  • Efficiency, Organizational
  • Endpoint Determination
  • Equipment Design
  • Factor Analysis, Statistical
  • Family relationships
  • Gels
  • Gene Expression
  • Genes, Immunoglobulin
  • Genetic Predisposition to Disease
  • Genetics, Medical
  • Genotype
  • Germany
  • Graft vs Host Disease
  • HIV Infections
  • Hispanic Americans
  • Individualized Medicine
  • Kaplan-Meier Estimate
  • Ketoconazole
  • Lasso
  • Logistic Models
  • Lymphokines
  • Mining
  • Models, Biological
  • Models, Statistical
  • Models, Theoretical
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Multivariate Analysis
  • Mutation
  • Neoplasms, Hormone-Dependent
  • Nomograms
  • Odds Ratio
  • Outcome Assessment (Health Care)
  • Ovarian Neoplasms
  • Personalized medicine
  • Population
  • Population Surveillance
  • Predictive Value of Tests
  • Pregnancy
  • Probability
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Randomized Controlled Trials as Topic
  • Receptors, Progesterone
  • Registries
  • Reproducibility of Results
  • Research Design
  • Residence Characteristics
  • Retrospective Studies
  • Ribosomal Protein S6 Kinases
  • Risk
  • Risk Assessment
  • Risk Factors
  • Sample Size
  • Selective Estrogen Receptor Modulators
  • Sensitivity and Specificity
  • Statistics as Topic
  • Survival
  • Survival Analysis
  • Survival Rate
  • Tamoxifen
  • Translocation, Genetic
  • Treatment Failure
  • Treatment Outcome
  • Tumor Markers, Biological
  • United States
  • Urologic Neoplasms
  • Validation Studies as Topic
  • Vascular Endothelial Growth Factors