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Saint Louis Park, MN, United States

Merchan J.R.,University of Miami | Qin R.,Mayo Medical School | Pitot H.,Mayo Medical School | Picus J.,University of Washington | And 5 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015

Purpose: Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods: In the phase I portion, eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression-free rate. Secondary endpoints were response rate, toxicity evaluation, and PFS and OS. Results: Maximum tolerated dose was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). The 6-month progression-free rate was 40 % (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response, stable disease, and progressive disease were seen in 23, 63, and 14 % of patients, respectively. Most common grade 3-4 AEs included fatigue (17.8 %), hypertriglyceridemia (11.1 %), stomatitis (8.9 %), proteinuria (8.9 %), abdominal pain (6.7 %), and anemia (6.7 %). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions: Temsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. © 2015 Springer-Verlag Berlin Heidelberg. Source


Kozloff M.F.,University of Chicago | Berlin J.,Vanderbilt Ingram Cancer Center | Flynn P.J.,Metro Minnesota CCOP | Kabbinavar F.,University of California at Los Angeles | And 4 more authors.
Oncology | Year: 2010

Background: Elderly patients are underrepresented in clinical trials and frequently undertreated with standard therapy. The BRiTE observational cohort study assessed the safety and effectiveness of bevacizumab-based first-line therapy for metastatic colorectal cancer among a large cohort of elderly patients (896 patients ≥65 years, among 1,953 total patients). Methods: Treatment patterns, safety, progression-free survival (PFS), overall survival (OS) and survival beyond first progression (SBP) were analyzed by age cohorts. OS and SBP were further analyzed using Cox proportional hazards regression. Results: Median PFS (months) was similar across age cohorts (<65 years, 9.8; 65 to <75, 9.6; 75 to <80, 10.0; ≥80, 8.6). Median OS (months) decreased with age (<65 years, 26.0; 65 to <75, 21.1; 75 to <80, 20.3; ≥80, 16.2). SBP declined with age; however, a Cox model adjusting for baseline and postbaseline covariates that were imbalanced among age cohorts showed a reduced independent effect of age on SBP (months) (<65 years, 12.0; 65 to <75, 11.4; 75 to <80, 11.3; ≥80, 10.0) compared with unadjusted analyses. Use of bevacizumab in subsequent postprogression regimens decreased with age. Incidence of targeted adverse events did not increase with age, except for arterial thromboembolic events (ATEs), for which Eastern Cooperative Oncology Group performance status, anticoagulation and arterial disease history were stronger prognostic factors than age. Conclusions: Elderly patients receiving bevacizumab with first-line chemotherapy showed treatment benefit, although there was reduced median survival with increasing age. There was no increased toxicity among elderly patients, except for risk of ATEs. Copyright © 2010 S. Karger AG, Basel. Source


Knox J.J.,University of Toronto | Qin R.,Mayo Medical School | Strosberg J.R.,H. Lee Moffitt Cancer Center and Research Institute | Tan B.,University of Washington | And 6 more authors.
Investigational New Drugs | Year: 2015

Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule. © 2014 Springer Science+Business Media New York. Source


Ryan J.L.,University of Rochester | Heckler C.E.,University of Rochester | Roscoe J.A.,University of Rochester | Dakhil S.R.,Witchita CCOP | And 4 more authors.
Supportive Care in Cancer | Year: 2012

Purpose Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy. Methods In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 1.5 g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT3 receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale ("1"="Not at all Nauseated" and "7"="Extremely Nauseated") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy. Results A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p=0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p=0.017 and p=0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p<0.0001). Conclusions Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients. © 2011 Springer-Verlag. Source


Kirshner J.J.,Hematology Oncology Associates of Central New York | Heckler C.E.,University of Rochester | Janelsins M.C.,University of Rochester | Dakhil S.R.,Wichita CCOP | And 3 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: Pegfilgrastim-induced bone pain is a significant clinical problem that may result in discontinuation of pegfilgrastim and lead to less effective chemotherapy dosing. Interventions for pegfilgrastim-induced bone pain are needed. Patients and Methods: The University of Rochester Cancer Center Clinical Community Oncology Program Research Base randomly assigned 510 patients at 17 sites to receive either naproxen (500 mg two times per day) or placebo on the day of pegfilgrastim administration, continuing for 5 to 8 days after pegfilgrastim. Patients recorded pain severity (using a scale of 0 to 10) and duration in daily diaries. The primary outcome measure was the area under the curve (AUC) for pain for days 1 through 5. Secondary outcome measures included the identification of risk factors for the development of pain and response to naproxen. Results Patients' mean age was 55.6 years and 86% were female. Sixty-eight percent of patients had breast cancer and 10% had lung cancer. Pain reached its peak at 3 days for both groups. The mean AUC for pain was 7.71 for the placebo group and 6.04 for the naproxen group (P = .037). Naproxen reduced maximum pain from 3.40 to 2.59 (P = .005). Naproxen also reduced overall pain incidence from 71.3% to 61.1% (P = .020) and duration from 2.40 to 1.92 days (P = .009). The reduction in severe pain (> 5 on a scale of 1 to 10) from 27.0% to 19.2% was also significant (P = .048). Risk factors could not be identified to predict incidence, severity, or ability to prevent pegfilgrastiminduced bone pain. Conclusion: Our phase III randomized placebo-controlled clinical trial demonstrated that naproxen at a dose of 500 mg twice per day is effective in reducing the incidence and severity of pegfilgrastim-induced bone pain. © 2012 by American Society of Clinical Oncology. Source

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