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Uronis, Hope Elizabeth

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2000

M.D. — State University of New York at Buffalo

Grants:

A Randomized multicenter double blind Phase III study of Nivolumab or placebo in subjects with resected esophageal junction cancer.

Administered By
Duke Cancer Institute
AwardedBy
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
July 01, 2016
End Date
June 30, 2021

A Multicenter randomized open label study in patients with esophageal cancer refractory or intorlerant to combination therapy with fluoropyrimidine

Administered By
Duke Cancer Institute
AwardedBy
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
May 01, 2016
End Date
April 30, 2021

A Phase 1b/2 open label dose escalation study of Margetuximab incombination with Pembrolizumab in patients with relapsed refrectory advanced HER2 + Gastroesophageal junction or gastric cancer.

Administered By
Duke Cancer Institute
AwardedBy
MacroGenics, Inc.
Role
Principal Investigator
Start Date
January 01, 2016
End Date
December 31, 2020

A Phase 2 study of ADXS11-001 i subjects with persistent/recurrent loco-regional or metastatic squamous cell carcinoma of the anorectal canal.

Administered By
Duke Cancer Institute
AwardedBy
Advaxis Inc
Role
Principal Investigator
Start Date
November 01, 2015
End Date
October 31, 2020
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Publications:

Role of Chemotherapy and Radiation Therapy in the Management of Gastric Adenocarcinoma.

Gastric adenocarcinoma is the fifth most common cancer worldwide and is often diagnosed at a late stage with nearly 50% of patients having locally advanced, unresectable, or metastatic disease at the time of presentation. Efforts to improve outcomes in patients with resected and unresectable gastric cancer with various chemotherapy and radiation regimens are ongoing. Appropriate evaluation and management is often not straightforward and requires the input of a multidisciplinary team. There is no consensus as to the best approach for treatment of gastric cancer; however, the available data and our institutional approach to the management of gastric cancer are discussed.

Authors
Spiegel, D; Palta, M; Uronis, H
MLA Citation
Spiegel, D, Palta, M, and Uronis, H. "Role of Chemotherapy and Radiation Therapy in the Management of Gastric Adenocarcinoma." The Surgical clinics of North America 97.2 (April 2017): 421-435.
PMID
28325195
Source
epmc
Published In
Surgical Clinics of North America
Volume
97
Issue
2
Publish Date
2017
Start Page
421
End Page
435
DOI
10.1016/j.suc.2016.11.013

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

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

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

The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer.

The optimal approach to patients with locally recurrent, non-metastatic rectal cancer is unclear. This study evaluates the outcomes and toxicity associated with pelvic re-irradiation.Patients undergoing re-irradiation for locally recurrent, non-metastatic, rectal cancer between 2000 and 2014 were identified. Acute and late toxicities were assessed using common terminology criteria for adverse events version 4.0. Disease-related endpoints included palliation of local symptoms, surgical outcomes, and local progression-free survival (PFS), distant PFS and overall survival (OS) using the Kaplan-Meier method.Thirty-three patients met the criteria for inclusion in this study. Two (6 %) experienced early grade 3+ toxicity and seven (21 %) experienced late grade 3+ toxicity. Twenty-three patients presented with symptomatic local recurrence and 18 (78 %) reported symptomatic relief. Median local PFS was 8.7 (95 % CI 3.8-15.2) months, with a 2-year rate of 15.7 % (4.1-34.2), and median time to distant progression was 4.4 (2.2-33.3) months, with a 2-year distant PFS rate of 38.9 % (20.1-57.3). Median OS time for patients was 23.1 (11.1-33.0) months. Of the 14 patients who underwent surgery, median survival was 32.3 (13.8-48.0) months compared with 13.3 (2.2-33.0) months in patients not undergoing surgery (p = 0.10). A margin-negative (R0) resection was achieved in 10 (71 %) of the surgeries. Radiation treatment modality (intensity-modulated radiation therapy, three-dimensional conformal radiotherapy, intraoperative radiation therapy) did not influence local or distant PFS or OS.Re-irradiation is a beneficial treatment modality for the management of locally recurrent, non-metastatic rectal cancer. It is associated with symptom improvement, low rates of toxicity, and similar benefits among radiation modalities.

Authors
Susko, M; Lee, J; Salama, J; Thomas, S; Uronis, H; Hsu, D; Migaly, J; Willett, C; Czito, B; Palta, M
MLA Citation
Susko, M, Lee, J, Salama, J, Thomas, S, Uronis, H, Hsu, D, Migaly, J, Willett, C, Czito, B, and Palta, M. "The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer." Annals of surgical oncology 23.11 (October 2016): 3609-3615.
PMID
27169769
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
11
Publish Date
2016
Start Page
3609
End Page
3615
DOI
10.1245/s10434-016-5250-z

Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer.American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events.Twenty-four randomized controlled trials met the systematic review criteria.A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

Authors
Sohal, DPS; Mangu, PB; Khorana, AA; Shah, MA; Philip, PA; O'Reilly, EM; Uronis, HE; Ramanathan, RK; Crane, CH; Engebretson, A; Ruggiero, JT; Copur, MS; Lau, M; Urba, S; Laheru, D
MLA Citation
Sohal, DPS, Mangu, PB, Khorana, AA, Shah, MA, Philip, PA, O'Reilly, EM, Uronis, HE, Ramanathan, RK, Crane, CH, Engebretson, A, Ruggiero, JT, Copur, MS, Lau, M, Urba, S, and Laheru, D. "Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.23 (August 2016): 2784-2796.
PMID
27247222
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
23
Publish Date
2016
Start Page
2784
End Page
2796
DOI
10.1200/jco.2016.67.1412

A randomized pilot trial of a videoconference couples communication intervention for advanced GI cancer

Authors
Porter, LS; Keefe, FJ; Baucom, DH; Olsen, M; Zafar, SY; Uronis, H
MLA Citation
Porter, LS, Keefe, FJ, Baucom, DH, Olsen, M, Zafar, SY, and Uronis, H. "A randomized pilot trial of a videoconference couples communication intervention for advanced GI cancer." Psycho-Oncology (2016): n/a-n/a.
Source
crossref
Published In
Psycho-Oncology
Publish Date
2016
Start Page
n/a
End Page
n/a
DOI
10.1002/pon.4121

Oxygen for relief of dyspnoea in people with chronic obstructive pulmonary disease who would not qualify for home oxygen: A systematic review and meta-analysis

We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register to determine whether oxygen relieves dyspnoea in mildly or non-hypoxemic COPD and included 18 randomised controlled trials (431 participants) in the meta-analysis using Cochrane methodology. Oxygen therapy reduced dyspnoea when compared with medical air; standardised mean difference -0.37 (95% CI -0.50 to -0.24; I2=14%). In a priori subgroup and sensitivity analyses, dyspnoea was reduced by continuous oxygen during exertion but not short-burst oxygen therapy. Continuous exertional oxygen can relieve dyspnoea in mildly or non-hypoxemic COPD, but evidence from larger clinical trials is needed.

Authors
Uronis, HE; Ekström, MP; Currow, DC; McCrory, DC; Samsa, GP; Abernethy, AP
MLA Citation
Uronis, HE, Ekström, MP, Currow, DC, McCrory, DC, Samsa, GP, and Abernethy, AP. "Oxygen for relief of dyspnoea in people with chronic obstructive pulmonary disease who would not qualify for home oxygen: A systematic review and meta-analysis." Thorax 70.5 (May 1, 2015): 492-494.
Source
scopus
Published In
Thorax
Volume
70
Issue
5
Publish Date
2015
Start Page
492
End Page
494
DOI
10.1136/thoraxjnl-2014-205720

Oxygen for relief of dyspnoea in people with chronic obstructive pulmonary disease who would not qualify for home oxygen: a systematic review and meta-analysis.

We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register to determine whether oxygen relieves dyspnoea in mildly or non-hypoxemic COPD and included 18 randomised controlled trials (431 participants) in the meta-analysis using Cochrane methodology. Oxygen therapy reduced dyspnoea when compared with medical air; standardised mean difference -0.37 (95% CI -0.50 to -0.24; I(2)=14%). In a priori subgroup and sensitivity analyses, dyspnoea was reduced by continuous oxygen during exertion but not short-burst oxygen therapy. Continuous exertional oxygen can relieve dyspnoea in mildly or non-hypoxemic COPD, but evidence from larger clinical trials is needed.

Authors
Uronis, HE; Ekström, MP; Currow, DC; McCrory, DC; Samsa, GP; Abernethy, AP
MLA Citation
Uronis, HE, Ekström, MP, Currow, DC, McCrory, DC, Samsa, GP, and Abernethy, AP. "Oxygen for relief of dyspnoea in people with chronic obstructive pulmonary disease who would not qualify for home oxygen: a systematic review and meta-analysis." Thorax 70.5 (May 2015): 492-494.
PMID
25472664
Source
epmc
Published In
Thorax
Volume
70
Issue
5
Publish Date
2015
Start Page
492
End Page
494
DOI
10.1136/thoraxjnl-2014-205720

Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer.

TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer.Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m(2)), gemcitabine plus TH-302 240 mg/m(2) (G+T240), or gemcitabine plus TH-302 340 mg/m(2) (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety.Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (-5,398 v -549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302-related AEs but were not associated with treatment discontinuation.PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979).

Authors
Borad, MJ; Reddy, SG; Bahary, N; Uronis, HE; Sigal, D; Cohn, AL; Schelman, WR; Stephenson, J; Chiorean, EG; Rosen, PJ; Ulrich, B; Dragovich, T; Del Prete, SA; Rarick, M; Eng, C; Kroll, S; Ryan, DP
MLA Citation
Borad, MJ, Reddy, SG, Bahary, N, Uronis, HE, Sigal, D, Cohn, AL, Schelman, WR, Stephenson, J, Chiorean, EG, Rosen, PJ, Ulrich, B, Dragovich, T, Del Prete, SA, Rarick, M, Eng, C, Kroll, S, and Ryan, DP. "Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33.13 (May 2015): 1475-1481.
PMID
25512461
Source
epmc
Published In
Journal of Clinical Oncology
Volume
33
Issue
13
Publish Date
2015
Start Page
1475
End Page
1481
DOI
10.1200/jco.2014.55.7504

Biomarker signatures correlate with clinical outcome in refractory metastatic colorectal cancer patients receiving bevacizumab and everolimus.

A novel combination of bevacizumab and everolimus was evaluated in refractory colorectal cancer patients in a phase II trial. In this retrospective analysis, plasma samples from 49 patients were tested for over 40 biomarkers at baseline and after one or two cycles of drug administration. Analyte levels at baseline and change on-treatment were correlated with progression-free survival (PFS) and overall survival (OS) using univariate Cox proportional hazard modeling. Multivariable analyses were conducted using Cox modeling. Significant changes in multiple markers were observed following bevacizumab and everolimus treatment. Baseline levels of six markers significantly correlated with PFS and OS, including CRP, Gro-α, IGFBP-1, TF, ICAM-1, and TSP-2 (P < 0.05). At C2D1, changes of IGFBP-3, TGFβ-R3, and IGFBP-2 correlated with PFS and OS. Prognostic models were developed for OS and PFS (P = 0.0002 and 0.004, respectively). The baseline model for OS consisted of CRP, Gro-α, and TF, while the on-treatment model at C2D1 included IGFBP-2, IGFBP-3, and TGFβ-R3. These data demonstrated that multiple biomarkers were significantly modulated in response to bevacizumab and everolimus. Several markers correlated with both PFS and OS. Interestingly, these markers are known to be associated with inflammation and IGF signaling, key modulators of mTOR biology.

Authors
Liu, Y; Starr, MD; Brady, JC; Rushing, C; Bulusu, A; Pang, H; Honeycutt, W; Amara, A; Altomare, I; Uronis, HE; Hurwitz, HI; Nixon, AB
MLA Citation
Liu, Y, Starr, MD, Brady, JC, Rushing, C, Bulusu, A, Pang, H, Honeycutt, W, Amara, A, Altomare, I, Uronis, HE, Hurwitz, HI, and Nixon, AB. "Biomarker signatures correlate with clinical outcome in refractory metastatic colorectal cancer patients receiving bevacizumab and everolimus." Molecular cancer therapeutics 14.4 (April 2015): 1048-1056.
PMID
25695956
Source
epmc
Published In
Molecular cancer therapeutics
Volume
14
Issue
4
Publish Date
2015
Start Page
1048
End Page
1056
DOI
10.1158/1535-7163.mct-14-0923-t

A Phase I/biomarker study of bevacizumab in combination with CNTO 95 in patients with advanced solid tumors.

PURPOSE: Inhibition of tumor angiogenesis is an effective mechanism to limit tumor growth; dual inhibition may result in additional benefit. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), and intetumumab is a fully humanized monoclonal antibody that blocks αv integrins when complexed with β integrins. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus intetumumab in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis. METHODS: Patients with refractory solid tumors, Karnofsky performance status ≥70%, and adequate organ function were eligible. Plasma samples and wound biopsies were obtained at baseline and on-treatment. RESULTS: Twelve patients were enrolled and received study drug. No tumor responses were noted. Observed toxicities included three cases of transient uveitis likely related to intetumumab and one case of reversible posterior leukoencephalopathy syndrome likely related to bevacizumab. Biomarker analysis revealed changes in soluble endoglin, soluble E-cadherin, and soluble E-selectin as well as PlGF and VEGF-D while on treatment. There was no observed impact of bevacizumab plus intetumumab on the phosphorylated or total levels of paxillin in wound tissue; however, an increase in the ratio of phospho/total paxillin levels was noted. CONCLUSIONS: Bevacizumab and intetumumab can be administered safely in combination. Bevacizumab plus intetumumab treatment resulted in changes in the plasma levels of several extracellular matrix interacting proteins and angiogenic factors.

Authors
Uronis, HE; Jia, J; Bendell, JC; Howard, L; Ready, NA; Lee, PH; Starr, MD; Dellinger, A; Pang, H; Nixon, AB; Hurwitz, HI
MLA Citation
Uronis, HE, Jia, J, Bendell, JC, Howard, L, Ready, NA, Lee, PH, Starr, MD, Dellinger, A, Pang, H, Nixon, AB, and Hurwitz, HI. "A Phase I/biomarker study of bevacizumab in combination with CNTO 95 in patients with advanced solid tumors." Cancer chemotherapy and pharmacology 75.2 (February 2015): 343-352.
PMID
25527204
Source
epmc
Published In
Cancer Chemotherapy and Pharmacology
Volume
75
Issue
2
Publish Date
2015
Start Page
343
End Page
352
DOI
10.1007/s00280-014-2647-x

A Phase I/biomarker study of bevacizumab in combination with CNTO 95 in patients with advanced solid tumors

© Springer-Verlag 2014.Purpose: Inhibition of tumor angiogenesis is an effective mechanism to limit tumor growth; dual inhibition may result in additional benefit. Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), and intetumumab is a fully humanized monoclonal antibody that blocks αv integrins when complexed with β integrins. We evaluated the safety, tolerability, and efficacy of the combination of bevacizumab plus intetumumab in patients with refractory solid tumors. We also explored the effects of these agents on plasma-based biomarkers and wound angiogenesis. Methods: Patients with refractory solid tumors, Karnofsky performance status ≥70 %, and adequate organ function were eligible. Plasma samples and wound biopsies were obtained at baseline and on-treatment. Results: Twelve patients were enrolled and received study drug. No tumor responses were noted. Observed toxicities included three cases of transient uveitis likely related to intetumumab and one case of reversible posterior leukoencephalopathy syndrome likely related to bevacizumab. Biomarker analysis revealed changes in soluble endoglin, soluble E-cadherin, and soluble E-selectin as well as PlGF and VEGF-D while on treatment. There was no observed impact of bevacizumab plus intetumumab on the phosphorylated or total levels of paxillin in wound tissue; however, an increase in the ratio of phospho/total paxillin levels was noted. Conclusions: Bevacizumab and intetumumab can be administered safely in combination. Bevacizumab plus intetumumab treatment resulted in changes in the plasma levels of several extracellular matrix interacting proteins and angiogenic factors.

Authors
Uronis, HE; Jia, J; Bendell, JC; Howard, L; Ready, NA; Lee, PH; Starr, MD; Dellinger, A; Pang, H; Nixon, AB; Hurwitz, HI
MLA Citation
Uronis, HE, Jia, J, Bendell, JC, Howard, L, Ready, NA, Lee, PH, Starr, MD, Dellinger, A, Pang, H, Nixon, AB, and Hurwitz, HI. "A Phase I/biomarker study of bevacizumab in combination with CNTO 95 in patients with advanced solid tumors." Cancer Chemotherapy and Pharmacology 75.2 (January 1, 2015): 343-352.
Source
scopus
Published In
Cancer Chemotherapy and Pharmacology
Volume
75
Issue
2
Publish Date
2015
Start Page
343
End Page
352
DOI
10.1007/s00280-014-2647-x

Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience.

Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. Given high survival rates in stage I patients reported in small series with surgery alone, adjuvant chemoradiotherapy (CRT) has traditionally been recommended only for patients with high risk disease. Recent population-based data have demonstrated inferior outcomes to previous series. We examined disease-related outcomes for stage I tumors treated with pancreaticoduodenectomy, with and without CRT.All patients with stage I ampullary adenocarcinoma treated from 1976 to 2011 at Duke University were reviewed. Disease-related endpoints including local control (LC), metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.Forty-four patients were included in this study. Thirty-one patients underwent surgery alone, while 13 also received adjuvant CRT. Five-year LC, MFS, DFS and OS for patients treated with surgery only and surgery with CRT were 56% and 83% (P=0.13), 67% and 83% (P=0.31), 56% and 83% (P=0.13), and 53% and 68% (P=0.09), respectively.The prognosis for patients diagnosed with stage I ampullary adenocarcinoma may not be as favorable as previously described. Our data suggests a possible benefit of adjuvant CRT delivery.

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; McSherry, F; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, McSherry, F, Tyler, DS, Uronis, HE, and Czito, BG. "Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience." Journal of gastrointestinal oncology 5.6 (December 2014): 421-427.
PMID
25436120
Source
epmc
Published In
Journal of Gastrointestinal Oncology
Volume
5
Issue
6
Publish Date
2014
Start Page
421
End Page
427
DOI
10.3978/j.issn.2078-6891.2014.084

A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors.

PURPOSE: To investigate the safety, optimal dosing, pharmacokinetics and clinical activity of a regimen of navitoclax (ABT-263) combined with gemcitabine in patients with solid tumors. EXPERIMENTAL DESIGN: Patients with solid tumors for which gemcitabine was deemed an appropriate therapy were enrolled into one of two different dosing schedules (21-day dosing schedule: navitoclax administered orally on days 1-3 and 8-10,; and gemcitabine 1,000 mg/m(2) on days 1 and 8; 28-day dosing schedule: navitoclax administrated orally on days 1-3, 8-10, and 15-17; and gemcitabine 1,000 mg/m(2) on days 1, 8 and 15). Navitoclax doses were escalated from 150 to 425 mg. An expanded safety cohort was conducted for the 21-day dosing schedule at the maximum tolerated dose (MTD) of navitoclax. RESULTS: Forty-six patients were enrolled at three U.S. centers. The most common adverse events included: hematologic abnormalities (thrombocytopenia, neutropenia, and anemia), liver enzyme elevations (ALT and AST), and gastrointestinal disturbances (diarrhea, nausea, and vomiting). Dose-limiting toxicities (DLTs) observed in cycle 1 were grade 4 thrombocytopenia (2 patients), grade 4 neutropenia (1 patient), and grade 3 AST elevation (2 patients). The MTD of navitoclax was 325 mg co-administered with gemcitabine 1,000 mg/m(2) for the 21-day schedule. No clinically significant pharmacokinetic drug-drug interactions were observed. There were no objective responses. Stable disease, reported at the end of cycle 2, was the best response in 54 % of evaluable patients (n = 39). CONCLUSIONS: The combination of navitoclax 325 mg with gemcitabine 1,000 mg/m(2) was generally well tolerated and exhibited a favorable safety profile in patients with advanced solid tumors.

Authors
Cleary, JM; Lima, CMSR; Hurwitz, HI; Montero, AJ; Franklin, C; Yang, J; Graham, A; Busman, T; Mabry, M; Holen, K; Shapiro, GI; Uronis, H
MLA Citation
Cleary, JM, Lima, CMSR, Hurwitz, HI, Montero, AJ, Franklin, C, Yang, J, Graham, A, Busman, T, Mabry, M, Holen, K, Shapiro, GI, and Uronis, H. "A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors." Investigational new drugs 32.5 (October 2014): 937-945.
PMID
24916770
Source
epmc
Published In
Investigational New Drugs
Volume
32
Issue
5
Publish Date
2014
Start Page
937
End Page
945
DOI
10.1007/s10637-014-0110-9

Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.

To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients.This was a standard "3 + 3" dose-escalation trial. All subjects received bevacizumab 7.5 mg/kg on day 1 of each cycle. Doses for capecitabine, oxaliplatin and everolimus were modified per dose limiting toxicity (DLT). Baseline and on-treatment plasma biomarkers were analyzed. Archived tumor mRNA levels were evaluated for NRP1, NRP2 and VEGF-A isoforms.Twenty-nine patients were evaluable for toxicity and 30 for efficacy. Two DLTs were observed in cohort 1 and one DLT each was observed in cohort -1 and -1b. Grade ≥3 toxicities included neutropenia, hypertension, perforation/fistula/hemorrhage, hypertriglyceridemia, diarrhea, and thromboembolism. Twelve subjects experienced partial response (PR); 12 had stable disease as best response. Three of seven chemorefractory metastatic colorectal cancer (mCRC) subjects experienced PR; 8 of 15 chemonaive mCRC subjects experienced PR. Plasma TβRIII and IL-6 increased on treatment but without correlation to outcome. Increased VEGF165 levels significantly correlated with longer progression free survival.Everolimus with full dose capecitabine, oxaliplatin, and bevacizumab had unacceptable toxicity. MTD was: everolimus 5 mg daily; capecitabine 680 mg/m(2) BID days 1-14; oxaliplatin 100 mg/m(2) and bevacizumab 7.5 mg/kg, day 1. Activity was noted in mCRC.

Authors
Rangwala, F; Bendell, JC; Kozloff, MF; Arrowood, CC; Dellinger, A; Meadows, J; Tourt-Uhlig, S; Murphy, J; Meadows, KL; Starr, A; Broderick, S; Brady, JC; Cushman, SM; Morse, MA; Uronis, HE; Hsu, SD; Zafar, SY; Wallace, J; Starodub, AN; Strickler, JH; Pang, H; Nixon, AB; Hurwitz, HI
MLA Citation
Rangwala, F, Bendell, JC, Kozloff, MF, Arrowood, CC, Dellinger, A, Meadows, J, Tourt-Uhlig, S, Murphy, J, Meadows, KL, Starr, A, Broderick, S, Brady, JC, Cushman, SM, Morse, MA, Uronis, HE, Hsu, SD, Zafar, SY, Wallace, J, Starodub, AN, Strickler, JH, Pang, H, Nixon, AB, and Hurwitz, HI. "Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors." Investigational new drugs 32.4 (August 2014): 700-709.
PMID
24711126
Source
epmc
Published In
Investigational New Drugs
Volume
32
Issue
4
Publish Date
2014
Start Page
700
End Page
709
DOI
10.1007/s10637-014-0089-2

Patterns of recurrence after trimodality therapy for esophageal cancer.

Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined.All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery.Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%).Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes.

Authors
Dorth, JA; Pura, JA; Palta, M; Willett, CG; Uronis, HE; D'Amico, TA; Czito, BG
MLA Citation
Dorth, JA, Pura, JA, Palta, M, Willett, CG, Uronis, HE, D'Amico, TA, and Czito, BG. "Patterns of recurrence after trimodality therapy for esophageal cancer." Cancer 120.14 (July 2014): 2099-2105.
PMID
24711267
Source
epmc
Published In
Cancer
Volume
120
Issue
14
Publish Date
2014
Start Page
2099
End Page
2105
DOI
10.1002/cncr.28703

Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

PURPOSE: Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). METHODS: Patients were enrolled in a dose escalation cohort to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Using a "3 + 3" design, twelve patients with advanced solid tumors received dasatinib (50 mg twice daily or 70 mg daily), capecitabine (850 mg/m(2) twice daily, days 1-14), oxaliplatin (130 mg/m(2) on day 1) and bevacizumab (7.5 mg/kg on day1), every 3 weeks. Ten patients with previously untreated metastatic CRC were then enrolled in an expansion cohort. Activated src (src(act)) expression was measured by immunohistochemistry, using an antibody that selectively recognizes the active conformation of src (clone 28). RESULTS: Twenty-two patients were enrolled between June 2009 and May 2011. Two DLTs were observed in the 50 mg bid dasatinib cohort, and one DLT was observed in the 70 mg daily dasatinib cohort. The MTD and RP2D for dasatinib was 70 mg daily. The most common treatment-related adverse events were fatigue (20; 91 %) and diarrhea (18; 82 %). Biomarker analysis of src(act) expression demonstrated that the overall response rate (ORR) was 75 % (6/8) for patients with high src(act) expression (IHC ≥ 2), compared to 0 % (0/8) for patients with low srcact expression (IHC 0 or 1); (p = 0.007). CONCLUSIONS: The RP2D of dasatinib is 70 mg daily in combination with CapeOx/bevacizumab. High levels of srcact expression may predict those patients most likely to benefit from dasatinib.

Authors
Strickler, JH; McCall, S; Nixon, AB; Brady, JC; Pang, H; Rushing, C; Cohn, A; Starodub, A; Arrowood, C; Haley, S; Meadows, KL; Morse, MA; Uronis, HE; Blobe, GC; Hsu, SD; Zafar, SY; Hurwitz, HI
MLA Citation
Strickler, JH, McCall, S, Nixon, AB, Brady, JC, Pang, H, Rushing, C, Cohn, A, Starodub, A, Arrowood, C, Haley, S, Meadows, KL, Morse, MA, Uronis, HE, Blobe, GC, Hsu, SD, Zafar, SY, and Hurwitz, HI. "Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer." Invest New Drugs 32.2 (April 2014): 330-339.
PMID
24173967
Source
pubmed
Published In
Investigational New Drugs
Volume
32
Issue
2
Publish Date
2014
Start Page
330
End Page
339
DOI
10.1007/s10637-013-0042-9

Phase i study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer

Purpose Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). Methods Patients were enrolled in a dose escalation cohort to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Using a "3 + 3" design, twelve patients with advanced solid tumors received dasatinib (50 mg twice daily or 70 mg daily), capecitabine (850 mg/m2 twice daily, days 1-14), oxaliplatin (130 mg/m2 on day 1) and bevacizumab (7.5 mg/kg on day1), every 3 weeks. Ten patients with previously untreated metastatic CRC were then enrolled in an expansion cohort. Activated src (srcact) expression was measured by immunohistochemistry, using an antibody that selectively recognizes the active conformation of src (clone 28). Results Twenty-two patients were enrolled between June 2009 and May 2011. Two DLTs were observed in the 50 mg bid dasatinib cohort, and one DLT was observed in the 70 mg daily dasatinib cohort. The MTD and RP2D for dasatinib was 70 mg daily. The most common treatment-related adverse events were fatigue (20; 91 %) and diarrhea (18; 82 %). Biomarker analysis of srcact expression demonstrated that the overall response rate (ORR) was 75 % (6/8) for patients with high src act expression (IHC ≥ 2), compared to 0 % (0/8) for patients with low srcact expression (IHC 0 or 1); (p = 0.007). Conclusions The RP2D of dasatinib is 70 mg daily in combination with CapeOx/bevacizumab. High levels of srcact expression may predict those patients most likely to benefit from dasatinib. © 2013 Springer Science+Business Media New York.

Authors
Strickler, JH; McCall, S; Nixon, AB; Brady, JC; Pang, H; Rushing, C; Cohn, A; Starodub, A; Arrowood, C; Haley, S; Meadows, KL; Morse, MA; Uronis, HE; Blobe, GC; Hsu, SD; Zafar, SY; Hurwitz, HI
MLA Citation
Strickler, JH, McCall, S, Nixon, AB, Brady, JC, Pang, H, Rushing, C, Cohn, A, Starodub, A, Arrowood, C, Haley, S, Meadows, KL, Morse, MA, Uronis, HE, Blobe, GC, Hsu, SD, Zafar, SY, and Hurwitz, HI. "Phase i study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer." Investigational New Drugs 32.2 (January 1, 2014): 330-339.
Source
scopus
Published In
Investigational New Drugs
Volume
32
Issue
2
Publish Date
2014
Start Page
330
End Page
339
DOI
10.1007/s10637-013-0042-9

Patterns of recurrence after trimodality therapy for esophageal cancer

BACKGROUND Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined. METHODS All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery. RESULTS Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%). CONCLUSIONS Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes. © 2014 American Cancer Society.

Authors
Dorth, JA; Pura, JA; Palta, M; Willett, CG; Uronis, HE; D'Amico, TA; Czito, BG
MLA Citation
Dorth, JA, Pura, JA, Palta, M, Willett, CG, Uronis, HE, D'Amico, TA, and Czito, BG. "Patterns of recurrence after trimodality therapy for esophageal cancer." Cancer 120.14 (January 1, 2014): 2099-2105.
Source
scopus
Published In
Cancer
Volume
120
Issue
14
Publish Date
2014
Start Page
2099
End Page
2105
DOI
10.1002/cncr.28703

Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors

Purpose: To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. Design: This was a standard "3 + 3" dose-escalation trial. All subjects received bevacizumab 7.5 mg/kg on day 1 of each cycle. Doses for capecitabine, oxaliplatin and everolimus were modified per dose limiting toxicity (DLT). Baseline and on-treatment plasma biomarkers were analyzed. Archived tumor mRNA levels were evaluated for NRP1, NRP2 and VEGF-A isoforms. Results: Twenty-nine patients were evaluable for toxicity and 30 for efficacy. Two DLTs were observed in cohort 1 and one DLT each was observed in cohort -1 and -1b. Grade ≥3 toxicities included neutropenia, hypertension, perforation/fistula/hemorrhage, hypertriglyceridemia, diarrhea, and thromboembolism. Twelve subjects experienced partial response (PR); 12 had stable disease as best response. Three of seven chemorefractory metastatic colorectal cancer (mCRC) subjects experienced PR; 8 of 15 chemonaive mCRC subjects experienced PR. Plasma TβRIII and IL-6 increased on treatment but without correlation to outcome. Increased VEGF165 levels significantly correlated with longer progression free survival. Conclusions: Everolimus with full dose capecitabine, oxaliplatin, and bevacizumab had unacceptable toxicity. MTD was: everolimus 5 mg daily; capecitabine 680 mg/m2 BID days 1-14; oxaliplatin 100 mg/m2 and bevacizumab 7.5 mg/kg, day 1. Activity was noted in mCRC. © 2014 Springer Science+Business Media.

Authors
Rangwala, F; Bendell, JC; Kozloff, MF; Arrowood, CC; Dellinger, A; Meadows, J; Tourt-Uhlig, S; Murphy, J; Meadows, KL; Starr, A; Broderick, S; Brady, JC; Cushman, SM; Morse, MA; Uronis, HE; Hsu, SD; Zafar, SY; Wallace, J; Starodub, AN; Strickler, JH; Pang, H; Nixon, AB; Hurwitz, HI
MLA Citation
Rangwala, F, Bendell, JC, Kozloff, MF, Arrowood, CC, Dellinger, A, Meadows, J, Tourt-Uhlig, S, Murphy, J, Meadows, KL, Starr, A, Broderick, S, Brady, JC, Cushman, SM, Morse, MA, Uronis, HE, Hsu, SD, Zafar, SY, Wallace, J, Starodub, AN, Strickler, JH, Pang, H, Nixon, AB, and Hurwitz, HI. "Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors." Investigational New Drugs 32.4 (January 1, 2014): 700-709.
Source
scopus
Published In
Investigational New Drugs
Volume
32
Issue
4
Publish Date
2014
Start Page
700
End Page
709
DOI
10.1007/s10637-014-0089-2

A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors

© Springer Science+Business Media 2014.Summary Purpose: To investigate the safety, optimal dosing, pharmacokinetics and clinical activity of a regimen of navitoclax (ABT-263) combined with gemcitabine in patients with solid tumors. Experimental Design: Patients with solid tumors for which gemcitabine was deemed an appropriate therapy were enrolled into one of two different dosing schedules (21-day dosing schedule: navitoclax administered orally on days 1-3 and 8-10,; and gemcitabine 1,000 mg/m<sup>2</sup> on days 1 and 8; 28-day dosing schedule: navitoclax administrated orally on days 1-3, 8-10, and 15-17; and gemcitabine 1,000 mg/m<sup>2</sup> on days 1, 8 and 15). Navitoclax doses were escalated from 150 to 425 mg. An expanded safety cohort was conducted for the 21-day dosing schedule at the maximum tolerated dose (MTD) of navitoclax. Results: Forty-six patients were enrolled at three U.S. centers. The most common adverse events included: hematologic abnormalities (thrombocytopenia, neutropenia, and anemia), liver enzyme elevations (ALT and AST), and gastrointestinal disturbances (diarrhea, nausea, and vomiting). Dose-limiting toxicities (DLTs) observed in cycle 1 were grade 4 thrombocytopenia (2 patients), grade 4 neutropenia (1 patient), and grade 3 AST elevation (2 patients). The MTD of navitoclax was 325 mg co-administered with gemcitabine 1,000 mg/m<sup>2</sup> for the 21-day schedule. No clinically significant pharmacokinetic drug- drug interactions were observed. There were no objective responses. Stable disease, reported at the end of cycle 2, was the best response in 54 % of evaluable patients (n = 39). Conclusions: The combination of navitoclax 325 mg with gemcitabine 1,000 mg/m<sup>2</sup> was generally well tolerated and exhibited a favorable safety profile in patients with advanced solid tumors.

Authors
Cleary, JM; Lima, CMSR; Hurwitz, HI; Montero, AJ; Franklin, C; Yang, J; Graham, A; Busman, T; Mabry, M; Holen, K; Shapiro, GI; Uronis, H
MLA Citation
Cleary, JM, Lima, CMSR, Hurwitz, HI, Montero, AJ, Franklin, C, Yang, J, Graham, A, Busman, T, Mabry, M, Holen, K, Shapiro, GI, and Uronis, H. "A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors." Investigational New Drugs 32.5 (2014): 937-945.
Source
scival
Published In
Investigational New Drugs
Volume
32
Issue
5
Publish Date
2014
Start Page
937
End Page
945
DOI
10.1007/s10637-014-0110-9

Is follow-up CT imaging of the chest and abdomen necessary after preoperative neoadjuvant therapy in rectal cancer patients without evidence of metastatic disease at diagnosis?

AIM: Patients with rectal cancer often undergo multiple CT scans prior to surgical resection. We propose that in patients with locally advanced rectal cancer without evidence of metastatic disease at presentation, CT imaging of the chest and abdomen after preoperative neoadjuvant therapy does not change clinical information or surgical management. METHOD: An institutional review board-approved medical record review identified patients with contrast enhanced CT of the chest, abdomen and pelvis alone or in conjunction with (18)F-fluoro-2-deoxy-d-glucose/positron emission tomography imaging for staging of rectal cancer prior to and after neoadjuvant therapy. Eighty-eight patients were included in the study. Scans were reviewed for the presence of metastatic disease on initial and follow-up imaging prior to surgical resection. RESULTS: Seventy-six (86%) of 88 patients had no evidence of metastasis at presentation. None of these patients developed metastatic disease after neoadjuvant therapy. Twelve (14%) had metastases at presentation. No study patient developed metastatic disease in a new organ. CONCLUSION: Imaging after preoperative neoadjuvant therapy in rectal cancer does not change the designation of metastatic disease. Patients with locally advanced rectal adenocarcinoma without evidence of metastases may not benefit from repeat imaging of the chest and abdomen after neoadjuvant therapy.

Authors
Jaffe, TA; Neville, AM; Bashir, MR; Uronis, HE; Thacker, JM
MLA Citation
Jaffe, TA, Neville, AM, Bashir, MR, Uronis, HE, and Thacker, JM. "Is follow-up CT imaging of the chest and abdomen necessary after preoperative neoadjuvant therapy in rectal cancer patients without evidence of metastatic disease at diagnosis?." Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 15.11 (November 2013): e654-e658.
PMID
23910050
Source
epmc
Published In
Colorectal Disease
Volume
15
Issue
11
Publish Date
2013
Start Page
e654
End Page
e658
DOI
10.1111/codi.12372

The role of local excision in invasive adenocarcinoma of the ampulla of Vater.

BACKGROUND: Ampulla of Vater carcinomas are rare malignancies that have been traditionally treated with radical surgical resection. Given the mortality associated with pancreaticoduodenectomy, some patients may benefit from local resection. A single-institution outcomes analysis was performed to define the role of local resection. METHODS: Patients undergoing local resection (ampullectomy) for ampullary carcinomas at Duke University between 1976 and 2010 were analyzed retrospectively. Time-to-event analysis was conducted analyzing all patients undergoing surgery, with and without adjuvant chemoradiation therapy (CRT). Overall survival (OS), local control (LC), metastases-free survival (MFS), and disease-free survival (DFS) were studied using Kaplan-Meier analysis. RESULTS: A total of 17 patients with invasive carcinoma underwent ampullectomy. The 3-and 5-year LC, MFS, DFS and OS rates were 36% and 24%, 68% and 54%, 31% and 21%, and 35% and 21%, respectively. Patients receiving adjuvant CRT did not appear to have improved outcomes compared with surgery alone, although this group tended to have poorer histological grade, more advanced tumor staging and involved surgical margins. CONCLUSIONS: Ampullectomy for invasive ampullary adenocarcinomas is a safe procedure but does not offer satisfactory long-term results, mostly due to high local failure rates. Adjuvant CRT therapy does not appear to offer increased local control or survival benefit following ampullectomy, although these results may suffer from selection bias and small sample size. Local resection should be limited to benign ampullary lesions or patients with very small, early tumors with favorable histologic features where radical resection is not feasible.

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; Bulusu, A; Tyler, DS; White, RR; Uronis, HE; Pappas, TN; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, Bulusu, A, Tyler, DS, White, RR, Uronis, HE, Pappas, TN, and Czito, BG. "The role of local excision in invasive adenocarcinoma of the ampulla of Vater." J Gastrointest Oncol 4.1 (March 2013): 8-13.
PMID
23450004
Source
pubmed
Published In
Journal of Gastrointestinal Oncology
Volume
4
Issue
1
Publish Date
2013
Start Page
8
End Page
13
DOI
10.3978/j.issn.2078-6891.2012.055

Preoperative chemoradiotherapy for locally advanced gastric cancer.

BACKGROUND: To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer. METHODS: Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0. RESULTS: Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively. CONCLUSIONS: Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

Authors
Pepek, JM; Chino, JP; Willett, CG; Palta, M; Blazer Iii, DG; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Pepek, JM, Chino, JP, Willett, CG, Palta, M, Blazer Iii, DG, Tyler, DS, Uronis, HE, and Czito, BG. "Preoperative chemoradiotherapy for locally advanced gastric cancer. (Published online)" Radiat Oncol 8 (January 4, 2013): 6-.
PMID
23286735
Source
pubmed
Published In
Radiation Oncology
Volume
8
Publish Date
2013
Start Page
6
DOI
10.1186/1748-717X-8-6

A phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.

BACKGROUND: Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. METHODS: Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m(2) BID on days 1-14, and oxaliplatin 130 mg/m(2) with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor. RESULTS: Thirty-five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class-related toxicities. NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome. CONCLUSIONS: Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab-containing regimens in metastatic gastroesophageal cancer.

Authors
Uronis, HE; Bendell, JC; Altomare, I; Blobe, GC; Hsu, SD; Morse, MA; Pang, H; Zafar, SY; Conkling, P; Favaro, J; Arrowood, CC; Cushman, SM; Meadows, KL; Brady, JC; Nixon, AB; Hurwitz, HI
MLA Citation
Uronis, HE, Bendell, JC, Altomare, I, Blobe, GC, Hsu, SD, Morse, MA, Pang, H, Zafar, SY, Conkling, P, Favaro, J, Arrowood, CC, Cushman, SM, Meadows, KL, Brady, JC, Nixon, AB, and Hurwitz, HI. "A phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas." Oncologist 18.3 (2013): 271-272.
PMID
23485624
Source
pubmed
Published In
The oncologist
Volume
18
Issue
3
Publish Date
2013
Start Page
271
End Page
272
DOI
10.1634/theoncologist.2012-0404

Assessment of the psychometric properties of an English version of the cancer dyspnea scale in people with advanced lung cancer.

CONTEXT: Dyspnea is a poorly understood subjective sensation. Existing dyspnea measures fail to adequately address its multidimensionality. A Japanese group developed and validated the Cancer Dyspnea Scale (CDS) for assessing dyspnea in patients with advanced lung cancer. OBJECTIVES: We evaluated the validity and reliability of the English version of the CDS (CDS-E) that has 12 items and takes, on average, 140 seconds for individuals to complete. METHODS: Eligible patients had advanced lung cancer, consented, and were fluent in English. Participants completed a 100 mm visual analogue scale (VAS), the modified Borg scale, the CDS-E, the Hospital Anxiety and Depression Scale, and the Functional Assessment of Cancer Therapy--Lung quality-of-life scale. Demographic, radiographic, and treatment information were obtained from patients' medical records. RESULTS: One hundred twelve participants were enrolled at three sites in the U.S., Australia, and the U.K. Mean age was 64.5 years (SD 11.5); 90% were Caucasian, 68% had Eastern Cooperative Oncology Group performance status 0-1, and 50% had non-small cell carcinoma. All completed the CDS-E independently, without difficulty. The CDS-E had reasonable internal consistency overall (Cronbach's α = 0.71) and for each of the three factors (effort, anxiety, discomfort Cronbach's α = 0.80-0.84). CDS-E scores were significantly correlated with the 100mm VAS (r = 0.82; P < 0.001) and the modified Borg (r = 0.87; P < 0.001). After factor analysis, the CDS-E was revised by removing three items (r-CDS-E). CONCLUSION: The CDS-E and r-CDS-E are reliable and valid measures of the sensation and the psychological components of dyspnea, with the shorter version having similar psychometric properties.

Authors
Uronis, HE; Shelby, RA; Currow, DC; Ahmedzai, SH; Bosworth, HB; Coan, A; Abernethy, AP
MLA Citation
Uronis, HE, Shelby, RA, Currow, DC, Ahmedzai, SH, Bosworth, HB, Coan, A, and Abernethy, AP. "Assessment of the psychometric properties of an English version of the cancer dyspnea scale in people with advanced lung cancer." J Pain Symptom Manage 44.5 (November 2012): 741-749.
PMID
22765966
Source
pubmed
Published In
Journal of Pain and Symptom Management
Volume
44
Issue
5
Publish Date
2012
Start Page
741
End Page
749
DOI
10.1016/j.jpainsymman.2011.10.027

Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors.

PURPOSE: To define the maximum tolerated dose, clinical toxicities, and pharmacodynamics of bevacizumab, everolimus, and panobinostat (LBH-589) when administered in combination to patients with advanced solid tumor malignancies. EXPERIMENT DESIGN: Subjects received 10 mg of panobinostat three times weekly, 5 or 10 mg everolimus daily, and bevacizumab at 10 mg/kg every 2 weeks. Dose-limiting toxicities (DLTs) were assessed in cycle 1; toxicity evaluation was closely monitored throughout treatment. Treatment continued until disease progression or undesirable toxicity. Protein acetylation was assessed in peripheral blood mononuclear cells (PBMC) both at baseline and on treatment. RESULTS: Twelve subjects were evaluable for toxicity and nine subjects for response. DLTs in cohort 1 included grade 2 esophagitis and grade 3 oral mucositis; DLTs in cohort -1 were grade 2 ventricular arrhythmia and grade 2 intolerable skin rash. Common adverse events were diarrhea (50 %), headache (33 %), mucositis/stomatitis (25 %), hyperlipidemia (25 %), and thrombocytopenia (25 %). There was 1 partial response; an additional 2 subjects had stable disease as best response. No consistent changes in protein acetylation in PBMC were observed in samples available from eight patients on treatment compared with baseline. CONCLUSIONS: Bevacizumab, everolimus, and panobinostat in combination at the lowest proposed doses did not have an acceptable safety and tolerability profile and did not consistently inhibit HDAC activity; therefore, we do not recommend further evaluation.

Authors
Strickler, JH; Starodub, AN; Jia, J; Meadows, KL; Nixon, AB; Dellinger, A; Morse, MA; Uronis, HE; Marcom, PK; Zafar, SY; Haley, ST; Hurwitz, HI
MLA Citation
Strickler, JH, Starodub, AN, Jia, J, Meadows, KL, Nixon, AB, Dellinger, A, Morse, MA, Uronis, HE, Marcom, PK, Zafar, SY, Haley, ST, and Hurwitz, HI. "Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors." Cancer Chemother Pharmacol 70.2 (August 2012): 251-258.
PMID
22744359
Source
pubmed
Published In
Cancer Chemotherapy and Pharmacology
Volume
70
Issue
2
Publish Date
2012
Start Page
251
End Page
258
DOI
10.1007/s00280-012-1911-1

Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?

The objective of this study was to compare survival between all patients with radiographically resectable adenocarcinoma of the proximal pancreas who underwent preoperative chemoradiation therapy (PRE-OP CRT) or surgical exploration first (SURGERY) with "intention to resect." Pancreatic cancer patients who undergo resection after PREOP CRT live longer than patients who undergo resection without PREOP CRT, a difference that may be attributable to patient selection. We retrospectively identified 236 patients with pancreatic head adenocarcinoma seen between 1999 and 2007 with sufficient data to be confirmed medically and radiographically resectable. The outcomes of 144 patients who underwent PREOP CRT were compared to those of 92 patients who proceeded straight to SURGERY. The groups were similar in age and gender. Tumors were slightly larger in the PREOP CRT group (mean 2.5 cm vs. 2.1 cm, P < 0.01), and there were trends toward more venous abutment (54% vs. 39%, P = 0.06) and a higher Charlson comorbidity index (P = 0.1). In the PREOP CRT group, 76 patients (53%) underwent resection, 28 (19%) had metastatic and 17 (12%) locally unresectable disease after PREOP CRT, and 23 (16%) were not explored due to performance status or loss to follow-up. In the SURGERY group, 68 patients (74%) underwent resection. Sixteen patients (17%) had metastatic and eight patients (9%) locally unresectable disease at exploration. In patients who underwent resection, the PREOP CRT group had smaller pathologic tumor size and lower incidence of positive lymph nodes than the SURGERY group but no difference in positive margins or need for vascular resection. Median overall survival (OS) in patients undergoing resection was 27 months in the PREOP CRT group and 17 months in the SURGERY group (P = 0.04). Median OS in all patients treated with PREOP CRT or surgically explored with intention to resect was 15 and 13 months, respectively, with superimposable survival curves. Despite a lower resection rate, the PREOP CRT group as a whole had a similar OS to the SURGERY group as a whole. For patients who underwent resection, those in the PREOP CRT had longer survival than those in the SURGERY group, suggesting that PREOP CRT allows better patient selection for resection. PREOP CRT should be considered an acceptable alternative for most patients with resectable pancreatic cancer.

Authors
Papalezova, KT; Tyler, DS; Blazer, DG; Clary, BM; Czito, BG; Hurwitz, HI; Uronis, HE; Pappas, TN; Willett, CG; White, RR
MLA Citation
Papalezova, KT, Tyler, DS, Blazer, DG, Clary, BM, Czito, BG, Hurwitz, HI, Uronis, HE, Pappas, TN, Willett, CG, and White, RR. "Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?." J Surg Oncol 106.1 (July 1, 2012): 111-118.
PMID
22311829
Source
pubmed
Published In
Journal of Surgical Oncology
Volume
106
Issue
1
Publish Date
2012
Start Page
111
End Page
118
DOI
10.1002/jso.23044

A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors.

PURPOSE: Preclinical data suggest concurrent inhibition of VEGF, mTOR and EGFR pathways may augment antitumor and antiangiogenic effects compared to inhibition of each pathway alone. This study evaluated the maximum tolerated dose/recommended phase II dose and safety and tolerability of bevacizumab, everolimus and panitumumab drug combination. METHODS: Subjects with advanced solid tumors received escalating doses of everolimus and flat dosing of panitumumab at 4.8 mg/kg and bevacizumab at 10 mg/kg every 2 weeks. Dose-limiting toxicities (DLTs) were assessed in cycle 1; toxicity evaluation was closely monitored throughout treatment. Treatment continued until disease progression or undesirable toxicity. RESULTS: Thirty-two subjects were evaluable for toxicity; 31 subjects were evaluable for tumor response. DLTs were observed in cohorts with everolimus at 10 and 5 mg daily and included grade 3 mucositis, skin rash and thrombocytopenia. Therefore, everolimus was dose-reduced to 5 mg three times weekly, which improved the tolerability of the treatment regimen. Common adverse events were skin rash/pruritus (91 %), mucositis/stomatitis (75 %), hypomagnesemia (72 %), hypocalcemia (56 %) and hypokalemia (50 %). There were 3 partial responses; an additional 10 subjects had stable disease ≥6 months. Three subjects with ovarian cancer and one with endometrial cancer achieved prolonged disease control ranging from 11 to >40 months. CONCLUSIONS: The recommended phase II dose is everolimus at 5 mg three times weekly plus panitumumab at 4.8 mg/kg and bevacizumab at 10 mg/kg every 2 weeks. This dosing regimen has an acceptable safety and tolerability profile and appears to have moderate the clinical activity in refractory tumors.

Authors
Vlahovic, G; Meadows, KL; Uronis, HE; Morse, MA; Blobe, GC; Riedel, RF; Zafar, SY; Alvarez-Secord, A; Gockerman, J; Starodub, AN; Ready, NE; Anderson, EL; Bendell, JC; Hurwitz, HI
MLA Citation
Vlahovic, G, Meadows, KL, Uronis, HE, Morse, MA, Blobe, GC, Riedel, RF, Zafar, SY, Alvarez-Secord, A, Gockerman, J, Starodub, AN, Ready, NE, Anderson, EL, Bendell, JC, and Hurwitz, HI. "A phase I study of bevacizumab, everolimus and panitumumab in advanced solid tumors." Cancer Chemother Pharmacol 70.1 (July 2012): 95-102.
PMID
22638798
Source
pubmed
Published In
Cancer Chemotherapy and Pharmacology
Volume
70
Issue
1
Publish Date
2012
Start Page
95
End Page
102
DOI
10.1007/s00280-012-1889-8

Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy.

BACKGROUND: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. METHODS: A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. RESULTS: A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. CONCLUSIONS: Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.

Authors
Palta, M; Patel, P; Broadwater, G; Willett, C; Pepek, J; Tyler, D; Zafar, SY; Uronis, H; Hurwitz, H; White, R; Czito, B
MLA Citation
Palta, M, Patel, P, Broadwater, G, Willett, C, Pepek, J, Tyler, D, Zafar, SY, Uronis, H, Hurwitz, H, White, R, and Czito, B. "Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy." Ann Surg Oncol 19.5 (May 2012): 1535-1540.
PMID
22045467
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
19
Issue
5
Publish Date
2012
Start Page
1535
End Page
1540
DOI
10.1245/s10434-011-2117-1

Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma.

PURPOSE: Extrahepatic cholangiocarcinoma is an uncommon but lethal malignancy. We analyzed the role of definitive chemoradiotherapy for patients with nonmetastatic, locally advanced extrahepatic cholangiocarcinoma treated at a single institution. METHODS AND MATERIALS: This retrospective analysis included 37 patients who underwent external beam radiation therapy (EBRT) with concurrent chemotherapy and/or brachytherapy (BT) for locally advanced extrahepatic cholangiocarcinoma. Local control (LC) and overall survival (OS) were assessed, and univariate regression analysis was used to evaluate the effects of patient- and treatment-related factors on clinical outcomes. RESULTS: Twenty-three patients received EBRT alone, 8 patients received EBRT plus BT, and 6 patients received BT alone (median follow-up of 14 months). Two patients were alive without evidence of recurrence at the time of analysis. Actuarial OS and LC rates at 1 year were 59% and 90%, respectively, and 22% and 71%, respectively, at 2 years. Two patients lived beyond 5 years without evidence of recurrence. On univariate analysis, EBRT with or without BT improved LC compared to BT alone (97% vs. 56% at 1 year; 75% vs. 56% at 2 years; p = 0.096). Patients who received EBRT alone vs. BT alone also had improved LC (96% vs. 56% at 1 year; 80% vs. 56% at 2 years; p = 0.113). Age, gender, tumor location (proximal vs. distal), histologic differentiation, EBRT dose (≤ or >50 Gy), EBRT planning method (two-dimensional vs. three-dimensional), and chemotherapy were not associated with patient outcomes. CONCLUSIONS: Patients with locally advanced extrahepatic cholangiocarcinoma have poor survival. Long-term survival is rare. The majority of patients treated with EBRT had local control at the time of death, suggesting that symptoms due to the local tumor effect might be effectively controlled with radiation therapy, and EBRT is an important element of treatment. Novel treatment approaches are indicated in the therapy for this disease.

Authors
Ghafoori, AP; Nelson, JW; Willett, CG; Chino, J; Tyler, DS; Hurwitz, HI; Uronis, HE; Morse, MA; Clough, RW; Czito, BG
MLA Citation
Ghafoori, AP, Nelson, JW, Willett, CG, Chino, J, Tyler, DS, Hurwitz, HI, Uronis, HE, Morse, MA, Clough, RW, and Czito, BG. "Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma." Int J Radiat Oncol Biol Phys 81.3 (November 1, 2011): 654-659.
PMID
20864265
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
81
Issue
3
Publish Date
2011
Start Page
654
End Page
659
DOI
10.1016/j.ijrobp.2010.06.018

Symptomatic oxygen for non-hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Dyspnoea is a common symptom in chronic obstructive pulmonary disease (COPD). People who are hypoxaemic may be given long-term oxygen relief therapy (LTOT) to improve their life expectancy and quality of life. However, the symptomatic benefit of home oxygen therapy in mildly or non-hypoxaemic people with COPD with dyspnoea who do not meet international funding criteria for LTOT (PaO(2)< 55 mmHg or other special cases) is unknown. OBJECTIVES: To determine the efficacy of oxygen versus medical air for relief of subjective dyspnoea in mildly or non-hypoxaemic people with COPD who would not otherwise qualify for home oxygen therapy. The main outcome was patient-reported dyspnoea and secondary outcome was exercise tolerance. SEARCH STRATEGY: We searched the Cochrane Airways Group Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, to November 2009, to identify randomised controlled trials. We handsearched reference lists of included articles. SELECTION CRITERIA: We only included randomised controlled trials of oxygen versus medical air in mildly or non-hypoxaemic people with COPD. Two review authors independently assessed articles for inclusion. DATA COLLECTION AND ANALYSIS: One review author completed data extraction and methodological quality assessment. A second review author then over-read evidence tables to assess for accuracy. MAIN RESULTS: Twenty-eight trials on 702 patients met the criteria for inclusion; 18 trials (431 participants) were included in the meta-analysis. Oxygen reduced dyspnoea with a standardised mean difference (SMD) of -0.37 (95% confidence interval (CI) -0.50 to -0.24, P < 0.00001). We observed significant heterogeneity. AUTHORS' CONCLUSIONS: Oxygen can relieve dyspnoea in mildly and non-hypoxaemic people with COPD who would not otherwise qualify for home oxygen therapy. Given the significant heterogeneity among the included studies, clinicians should continue to evaluate patients on an individual basis until supporting data from ongoing, large randomised controlled trials are available.

Authors
Uronis, H; McCrory, DC; Samsa, G; Currow, D; Abernethy, A
MLA Citation
Uronis, H, McCrory, DC, Samsa, G, Currow, D, and Abernethy, A. "Symptomatic oxygen for non-hypoxaemic chronic obstructive pulmonary disease. (Published online)" Cochrane Database Syst Rev 6 (June 15, 2011): CD006429-. (Review)
PMID
21678356
Source
pubmed
Published In
Cochrane database of systematic reviews (Online)
Issue
6
Publish Date
2011
Start Page
CD006429
DOI
10.1002/14651858.CD006429.pub2

A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE).

PURPOSE: VEGF, mTOR, and EGFR inhibitors have demonstrated anti-tumor and anti-angiogenic effects alone and in combination with each other. This study evaluated the safety, tolerability, and pharmacokinetics of bevacizumab, everolimus, and erlotinib combination. METHODS: Doublet therapy consisted of bevacizumab at 10 mg/kg every 14 days and everolimus 5 mg daily which escalated to 10 mg daily. Erlotinib 75 mg daily was added to the phase II dose recommended phase II dose (RPTD) of bevacizumab and everolimus. Dose-limiting toxicity (DLT) was assessed in cycle 1. RESULTS: Forty-eight patients with advanced solid malignancies were evaluable for DLT and efficacy. No DLTs were observed in the doublet dose escalation. Two DLTs (grade 3 mucositis and grade 3 rash) were observed with the addition of erlotinib 75 mg daily. Consequently, triplet doses were adjusted and were better tolerated. Four patients had a partial response. Median progression-free survival (PFS) for the doublet therapy was 6.0 months (0.5 to 32+ months) and 5.5 months (0.8 to 27+ months) for the triplet therapy. Systemic exposure of everolimus was significantly higher in combination with erlotinib (476 ± 161 ng h/mL) compared to when given alone (393 ± 156 ng h/mL; P = 0.020). CONCLUSIONS: The RPTD for the doublet therapy is bevacizumab 10 mg/kg every 14 days and everolimus 10 mg daily, and the RPTD for the triplet therapy is bevacizumab 5 mg/kg every 14 days, everolimus 5 mg and erlotinib 75 mg daily. Prolonged disease stability was demonstrated in tumors known to respond to mTOR inhibition and potentially resistant to VEGF blockade.

Authors
Bullock, KE; Petros, WP; Younis, I; Uronis, HE; Morse, MA; Blobe, GC; Zafar, SY; Gockerman, JP; Lager, JJ; Truax, R; Meadows, KL; Howard, LA; O'Neill, MM; Broadwater, G; Hurwitz, HI; Bendell, JC
MLA Citation
Bullock, KE, Petros, WP, Younis, I, Uronis, HE, Morse, MA, Blobe, GC, Zafar, SY, Gockerman, JP, Lager, JJ, Truax, R, Meadows, KL, Howard, LA, O'Neill, MM, Broadwater, G, Hurwitz, HI, and Bendell, JC. "A phase I study of bevacizumab (B) in combination with everolimus (E) and erlotinib (E) in advanced cancer (BEE)." Cancer Chemother Pharmacol 67.2 (February 2011): 465-474.
PMID
21079958
Source
pubmed
Published In
Cancer Chemotherapy and Pharmacology
Volume
67
Issue
2
Publish Date
2011
Start Page
465
End Page
474
DOI
10.1007/s00280-010-1507-6

A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.

PURPOSE: For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothelial growth factor and mammalian target of rapamycin inhibition has greater antiangiogenic and antitumor activity than either monotherapy. A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC. METHODS: Fifty patients with refractory mCRC were enrolled and received bevacizumab at 10 mg/kg every 2 weeks and everolimus at 10 mg orally daily. RESULTS: Of the 50 patients enrolled, the median age was 56 years and the median number of prior regimens was four. Forty-seven patients (96%) had prior bevacizumab exposure and 42 patients (84%) had documented progression on prior bevacizumab-based therapy. Forty-nine patients were evaluable for response; eight patients had minor responses (16%) and an additional 15 patients (30%) had stable disease (SD). No complete or partial responses were seen. The median progression-free survival interval was 2.3 months; however, 26% of patients achieved prolonged SD for ≥6 months, and three patients (6%) were on study for >1 year. The median overall survival duration was 8.1 months. The most common grade 1-2 toxicities were mucositis (68%) and hyperlipidemia (64%). Clinically significant grade ≥3 toxicities included hypertension (14%), fistula/abscess/perforation (8%), mucositis (6%), and hemorrhage (2%). CONCLUSIONS: Bevacizumab plus everolimus is generally tolerable but may have risks related to mucosal damage and/or wound healing. Bevacizumab plus everolimus appears to have modest activity in refractory mCRC in patients.

Authors
Altomare, I; Bendell, JC; Bullock, KE; Uronis, HE; Morse, MA; Hsu, SD; Zafar, SY; Blobe, GC; Pang, H; Honeycutt, W; Sutton, L; Hurwitz, HI
MLA Citation
Altomare, I, Bendell, JC, Bullock, KE, Uronis, HE, Morse, MA, Hsu, SD, Zafar, SY, Blobe, GC, Pang, H, Honeycutt, W, Sutton, L, and Hurwitz, HI. "A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer." Oncologist 16.8 (2011): 1131-1137.
PMID
21795432
Source
pubmed
Published In
The oncologist
Volume
16
Issue
8
Publish Date
2011
Start Page
1131
End Page
1137
DOI
10.1634/theoncologist.2011-0078

Validation of the Patient Care Monitor (Version 2.0): a review of system assessment instrument for cancer patients.

CONTEXT: The Patient Care Monitor (PCM) is a review of systems survey delivered by means of an electronic patient-reported outcomes (ePRO) data capture system that uses wireless tablet computers. Although the PCM 1.0 is validated, the updated PCM 2.0 has not been validated nor tested in the academic setting. OBJECTIVES: To validate and test the PCM 2.0 in three cancer populations. METHODS: Two hundred seventy-five individuals participated in three clinical trials enrolling breast (n=65), gastrointestinal (n=113), and lung (n=97) cancer patients. Internal consistency was evaluated using Cronbach's alpha coefficients calculated for six PCM subscales (general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation) and a Quality-of-Life Index. Construct validity was evaluated through Pearson's correlation between PCM subscales and subscales of the Functional Assessment of Cancer Therapy--General (FACT-G), the M.D. Anderson Symptom Inventory (MDASI), and the Functional Assessment of Chronic Illness Therapy--Fatigue (FACIT-F). The participants had the following characteristics: mean age was 58 years (standard deviation: 11), 52% were females, 79% were whites, 17% were blacks, 62% had no college degree, and 78% had metastatic or recurrent disease. RESULTS: Raw and normalized scores for PCM 2.0 subscales were internally consistent across study cohorts. PCM 2.0 subscales correlated significantly (P<0.05) with the corresponding subscales on FACT-G, MDASI, and FACIT-F, with the exception of FACT-G social well-being, particularly for the lung cancer population. These correlations demonstrated construct validity. PCM 2.0 results followed expected patterns by cancer etiology. Prior reports demonstrate patient satisfaction with PCM 2.0. CONCLUSION: Within three unique academic oncology populations, PCM 2.0 is a valid ePRO instrument for assessing symptoms with seven patient-centered subscale or index domains.

Authors
Abernethy, AP; Zafar, SY; Uronis, H; Wheeler, JL; Coan, A; Rowe, K; Shelby, RA; Fowler, R; Herndon, JE
MLA Citation
Abernethy, AP, Zafar, SY, Uronis, H, Wheeler, JL, Coan, A, Rowe, K, Shelby, RA, Fowler, R, and Herndon, JE. "Validation of the Patient Care Monitor (Version 2.0): a review of system assessment instrument for cancer patients." J Pain Symptom Manage 40.4 (October 2010): 545-558.
PMID
20579839
Source
pubmed
Published In
Journal of Pain and Symptom Management
Volume
40
Issue
4
Publish Date
2010
Start Page
545
End Page
558
DOI
10.1016/j.jpainsymman.2010.01.017

Management of dyspnea in patients with chronic obstructive pulmonary disease.

A progressive and debilitating illness, chronic obstructive pulmonary disease (COPD) has major worldwide impact. In addition to the care for underlying causes of disease, COPD treatment involves palliative intervention to address associated symptoms; in later stages of disease, when the underlying disease has been maximally treated, symptom management assumes primacy as the goal of care. Dyspnea is the most distressing symptom experienced by COPD patients. When dyspnea cannot be relieved by traditional COPD management strategies (i.e., "refractory dyspnea"), the goal of care shifts from prolonged survival to minimized symptoms, improved function, and enhanced quality of life. Numerous pharmacologic and non-pharmacologic interventions are available to achieve these goals, but supporting evidence is variable. This review summarizes options for managing refractory dyspnea in COPD patients, referring to the available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled frusemide, Heliox28, nutrition, psychosocial support, and breathing techniques.

Authors
Abernethy, AP; Uronis, HE; Wheeler, JL; Currow, DC
MLA Citation
Abernethy, AP, Uronis, HE, Wheeler, JL, and Currow, DC. "Management of dyspnea in patients with chronic obstructive pulmonary disease." Wien Med Wochenschr 159.23-24 (December 2009): 583-590. (Review)
PMID
20151347
Source
pubmed
Published In
Wiener Medizinische Wochenschrift
Volume
159
Issue
23-24
Publish Date
2009
Start Page
583
End Page
590
DOI
10.1007/s10354-009-0727-z

Quality management of potential chemotherapy-induced neutropenic complications: evaluation of practice in an academic medical center.

GOALS: Management of the risk of potential chemotherapy-induced neutropenic complications such as febrile neutropenia (FN) and severe neutropenia (SN) is a quality of care priority. How frequently does care at our institution conform to established guidelines? MATERIALS AND METHODS: This retrospective chart review study included a random sample of 305 cancer patients receiving care at a single US academic medical center. Abstracted data included demographics, risk factors, and outcome variables (e.g., development of FN/SN, administration of myeloid growth factors). To evaluate quality of care, we assessed conformance between actual practice and established clinical practice guidelines for the use of myeloid growth factors from the National Comprehensive Cancer Network (NCCN). MAIN RESULTS: Of the 305 cases reviewed, 8% were classified as low risk (<10%), 48% as intermediate risk (10-20%), and 44% as high risk (>20%), using the risk classifications in the NCCN guidelines modified to accommodate illness and other risk factors. Thirty-four percent received prophylactic administration of myeloid growth factors. Half of the cases had adequate documentation of mid-cycle absolute neutrophil count to determine whether FN/SN developed. Among these cases with adequate documentation, 21% developed FN/SN. Use of growth factors did not conform to established quality guidelines. Overall, 77 of 133 (58%) high-risk cases received myeloid growth factors, whereas six of 25 (24%) low-risk cases received myeloid growth factors. CONCLUSIONS: Routine clinical practice in this academic oncology setting was poorly aligned with established guidelines; there is substantial opportunity to standardize clinical strategies and increase conformance with evidence-based guidelines.

Authors
Abernethy, AP; Barbour, SY; Uronis, H; Zafar, SY; Coan, A; Rowe, K; Pupa, MR; Wheeler, JL; Herndon, JE
MLA Citation
Abernethy, AP, Barbour, SY, Uronis, H, Zafar, SY, Coan, A, Rowe, K, Pupa, MR, Wheeler, JL, and Herndon, JE. "Quality management of potential chemotherapy-induced neutropenic complications: evaluation of practice in an academic medical center." Support Care Cancer 17.6 (June 2009): 735-744.
PMID
19096882
Source
pubmed
Published In
Supportive Care in Cancer
Volume
17
Issue
6
Publish Date
2009
Start Page
735
End Page
744
DOI
10.1007/s00520-008-0562-6

Oxygen for relief of dyspnea: what is the evidence?

PURPOSE OF REVIEW: Refractory dyspnea is a common and distressing symptom complicating respiratory illness, including chronic obstructive pulmonary disease, and life-limiting illnesses in general, including cancer. Oxygen is often prescribed for relief of dyspnea and several consensus guidelines support this practice. The goal of this review is to outline the evidence for the use of oxygen for relief of dyspnea, with specific attention to situations in which oxygen is not already funded through long-term oxygen treatment guidelines (i.e., when PaO2 is >/=55 mmHg; also known as palliative oxygen). RECENT FINDINGS: Several recent systematic reviews, two focusing on people with chronic obstructive pulmonary disease and the other focusing on people with cancer, strengthen the evidence base behind the use of palliative oxygen for relief of refractory dyspnea, and support the observation that there are subgroups of people who benefit from oxygen, such as individuals with chronic obstructive pulmonary disease. SUMMARY: The data highlighted in this review support the belief that certain individuals benefit from the use of palliative oxygen but continue to suggest that definitive randomized trials are required to fully establish the benefit of palliative oxygen and to delineate characteristics predictive of benefit.

Authors
Uronis, HE; Abernethy, AP
MLA Citation
Uronis, HE, and Abernethy, AP. "Oxygen for relief of dyspnea: what is the evidence?." Curr Opin Support Palliat Care 2.2 (June 2008): 89-94. (Review)
PMID
18685402
Source
pubmed
Published In
Current Opinion in Supportive and Palliative Care
Volume
2
Issue
2
Publish Date
2008
Start Page
89
End Page
94
DOI
10.1097/SPC.0b013e3282ff0f5d

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis.

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.

Authors
Uronis, HE; Currow, DC; McCrory, DC; Samsa, GP; Abernethy, AP
MLA Citation
Uronis, HE, Currow, DC, McCrory, DC, Samsa, GP, and Abernethy, AP. "Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis." Br J Cancer 98.2 (January 29, 2008): 294-299. (Review)
Website
http://hdl.handle.net/10161/13711
PMID
18182991
Source
pubmed
Published In
British Journal of Cancer
Volume
98
Issue
2
Publish Date
2008
Start Page
294
End Page
299
DOI
10.1038/sj.bjc.6604161

Pharmacological management of breathlessness in advanced disease

Dyspnoea is one of the most distressing symptoms experienced by patients with life-limiting illnesses; when not relieved by disease management strategies it is termed 'refractory dyspnoea' and global palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though the level of evidence supporting their use varies. This narrative review provides a summary of pharmacological options for the management of refractory breathlessness, with a focus on those options with adequate supporting data; oxygen therapy is also considered as a potentially viable palliative measure. Currently available evidence is provided, highlighting areas for further investigation of selected approaches. The agents with adequate current evidence warranting inclusion as current 'best practices' are: oxygen, opioids, psychotropic drugs, inhaled frusemide, and Heliox 28. © 2008 W.S. Maney & Son Ltd.

Authors
Abernethy, AP; Uronis, HE; Wheeler, JL; Currow, DC
MLA Citation
Abernethy, AP, Uronis, HE, Wheeler, JL, and Currow, DC. "Pharmacological management of breathlessness in advanced disease." Progress in Palliative Care 16.1 (2008): 15-20.
Source
scival
Published In
Progress in Palliative Care
Volume
16
Issue
1
Publish Date
2008
Start Page
15
End Page
20
DOI
10.1179/096992608X291243

Anal cancer: an overview.

Anal cancer is a rare tumor with an incidence that has been rising over the last 25 years. The disease was once thought to develop as a result of chronic irritation, but it is now known that this is not the case. Multiple risk factors, including human papillomavirus (HPV) infection, anoreceptive intercourse, cigarette smoking, and immunosuppression, have been identified. HIV infection is also associated with anal cancer; there is a higher incidence in HIV-positive patients but the direct relationship between HIV and anal cancer has been difficult to separate from the prevalence of HPV in this population. HIV infection is also associated with anal cancer; there are increasing numbers of HIV-positive patients being diagnosed with the disease. Treatment of anal cancer prior to the 1970s involved abdominoperineal resection, but the standard of care is now concurrent chemoradiation therapy, with surgery reserved for those patients with residual disease. We present a case of anal cancer followed by a general discussion of both risk factors and treatment.

Authors
Uronis, HE; Bendell, JC
MLA Citation
Uronis, HE, and Bendell, JC. "Anal cancer: an overview." Oncologist 12.5 (May 2007): 524-534. (Review)
PMID
17522240
Source
pubmed
Published In
The oncologist
Volume
12
Issue
5
Publish Date
2007
Start Page
524
End Page
534
DOI
10.1634/theoncologist.12-5-524

Is bevacizumab effective and safe in combination with chemotherapy in patients with colorectal cancer?

Authors
Uronis, HE; Hurwitz, HI
MLA Citation
Uronis, HE, and Hurwitz, HI. "Is bevacizumab effective and safe in combination with chemotherapy in patients with colorectal cancer?." Nat Clin Pract Oncol 4.4 (April 2007): 214-215.
PMID
17297504
Source
pubmed
Published In
Nature Clinical Practice Oncology
Volume
4
Issue
4
Publish Date
2007
Start Page
214
End Page
215
DOI
10.1038/ncponc0748

Palliative oxygen for non-hypoxaemic chronic obstructive pulmonary disease

Authors
Uronis, HE; McCrory, DC; Samsa, GP; Currow, DC; Abernethy, A
MLA Citation
Uronis, HE, McCrory, DC, Samsa, GP, Currow, DC, and Abernethy, A. "Palliative oxygen for non-hypoxaemic chronic obstructive pulmonary disease." Cochrane Database of Systematic Reviews 2 (2007).
Source
scival
Published In
Cochrane database of systematic reviews (Online)
Issue
2
Publish Date
2007
DOI
10.1002/14651858.CD006429

Palliative management of refractory dyspnea in COPD.

COPD is a progressive illness with worldwide impact. Patients invariably reach a point at which they require palliative interventions. Dyspnea is the most distressing symptom experienced by these patients; when not relieved by traditional COPD management strategies it is termed "refractory dyspnea" and palliative approaches are required. The focus of care shifts from prolonging survival to reducing symptoms, increasing function, and improving quality of life. Numerous pharmacological and non-pharmacological interventions can achieve these goals, though evidence supporting their use is variable. This review provides a summary of the options for the management of refractory dyspnea in COPD, outlining currently available evidence and highlighting areas for further investigation. Topics include oxygen, opioids, psychotropic drugs, inhaled furosemide, Heliox, rehabilitation, nutrition, psychosocial support, breathing techniques, and breathlessness clinics.

Authors
Uronis, HE; Currow, DC; Abernethy, AP
MLA Citation
Uronis, HE, Currow, DC, and Abernethy, AP. "Palliative management of refractory dyspnea in COPD." Int J Chron Obstruct Pulmon Dis 1.3 (2006): 289-304. (Review)
PMID
18046866
Source
pubmed
Published In
International journal of chronic obstructive pulmonary disease
Volume
1
Issue
3
Publish Date
2006
Start Page
289
End Page
304
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Research Areas:

  • Adenocarcinoma
  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Ampulla of Vater
  • Anastomotic Leak
  • Angiogenesis Inhibitors
  • Aniline Compounds
  • Anoxia
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols
  • Anus Neoplasms
  • Anxiety
  • Bevacizumab
  • Carcinoma, Squamous Cell
  • Chemoradiotherapy
  • Chemoradiotherapy, Adjuvant
  • Colorectal Neoplasms
  • Combined Modality Therapy
  • Common Bile Duct Neoplasms
  • Depression
  • Esophagectomy
  • Female
  • Follow-Up Studies
  • Gastrointestinal Neoplasms
  • Humans
  • Hydroxamic Acids
  • Hypocalcemia
  • Hypokalemia
  • Immunosuppressive Agents
  • Injections, Intravenous
  • Kaplan-Meier Estimate
  • Language
  • Leukocytes, Mononuclear
  • Liver Neoplasms
  • Lymph Nodes
  • Lymphatic Irradiation
  • Male
  • Middle Aged
  • Models, Statistical
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local
  • Organoplatinum Compounds
  • Oxaliplatin
  • Pain Measurement
  • Palliative Care
  • Pancreatic Neoplasms
  • Patient Satisfaction
  • Photons
  • Platinum Compounds
  • Protein Kinase Inhibitors
  • Psychometrics
  • Pyrimidines
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Regression Analysis
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Sirolimus
  • Socioeconomic Factors
  • Sulfonamides
  • Survival Rate
  • Thiazoles
  • Tumor Markers, Biological
  • Young Adult