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Joshua A.M.,A+ Network | Shore N.D.,Urologic | Saad F.,University of Montreal | Chi K.N.,British Columbia Cancer Agency Vancouver Cancer Center | And 13 more authors.
Prostate | Year: 2015

BACKGROUND The open-label, single-arm enzalutamide expanded access program (EAP) in the United States and Canada evaluated the safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel. METHODS Patients (n = 507) received enzalutamide 160 mg/day until disease progression, intolerable adverse events (AEs), or commercial availability occurred. AEs and other safety variables were assessed on day 1, weeks 4 and 12, and every 12 weeks thereafter. Data following transition to commercial drug were not collected. RESULTS Median age was 71 years (range 43-97); 426 patients (83.9%) had a baseline ECOG score of ≤1. In addition to docetaxel, the majority of patients had received prior prostate cancer treatments such as abiraterone (76.1%) or cabazitaxel (28.6%). Median study treatment duration was 2.6 months (range 0.03-9.07). The most frequently reported reasons for discontinuation were commercial availability of enzalutamide (46.7%) and progressive disease (33.7%). A total of 88.2% of patients experienced AEs; 45.4% experienced AEs with a maximum grade of 1 or 2. Fatigue (39.1%), nausea (22.7%), and anorexia (14.8%) were the most commonly reported AEs. Seizure was reported in four patients (0.8%). The most commonly reported event leading to death was progression of metastatic prostate cancer (7.7%). CONCLUSION In this heavily pretreated EAP population with progressive mCRPC, enzalutamide was well tolerated and the safety profile was consistent with that of the AFFIRM trial. Prostate 75: 836-844, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Oechsle K.,University of Hamburg | Lorch A.,Justus Liebig University | Honecker F.,University of Hamburg | Kollmannsberger C.,British Columbia Cancer Agency Vancouver Cancer Center | And 4 more authors.
Oncology | Year: 2010

Objectives: We investigated the pattern of relapse after chemotherapy in patients with high-risk germ cell tumor (GCT) to critically review common follow-up procedures including close monitoring of serum tumor markers and radiologic procedures. Methods: 645 patients received first-line (434 patients) or salvage platinum-based (211 patients) high-dose chemotherapy in three multicenter trials. Retrospective analysis comprised 77 patients after first-line and 61 after salvage chemotherapy, who had achieved at least a partial remission but progressed afterwards. Results: At relapse, 24% of the patients presented with an isolated elevation in serum tumor markers, 26% with pathologic radiologic confirmation with negative tumor markers, and 42% with elevated tumor markers and radiologically confirmed progression. Relapse was detected by clinical symptoms in 8%. 46% relapsed within 3 months and 97% within 2 years. Relapse pattern did not correlate with tumor marker status or metastasis location prior to chemotherapy, line of chemotherapy, response status after chemotherapy or time point of relapse. Conclusion: In high-risk GCT patients, relapse after chemotherapy is detected either by tumor marker elevation alone, radiologic imaging alone or both, in one third each. Close monitoring including serum tumor markers, radiologic imaging and clinical examination appears warranted within the first 2 years. Copyright © 2010 S. Karger AG.

Renouf D.J.,University of Toronto | Moore M.J.,University of Toronto | Hedley D.,University of Toronto | Gill S.,British Columbia Cancer Agency Vancouver Cancer Center | And 9 more authors.
Investigational New Drugs | Year: 2012

Aim: This phase I/II study of saracatinib in combination with gemcitabine in patients with advanced pancreatic cancer was conducted by the NCIC Clinical Trials Group. The aims were to define the recommended phase II dose (RP2D) of saracatinib when combined with gemcitabine, and assess the efficacy of this combination in advanced pancreatic cancer. Patients and Methods: Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and no prior chemotherapy. In phase I saracatinib was escalated in combination with gemcitabine (1000 mg/m 2) to determine the recommended phase II dose (RP2D). The study was then expanded to a single arm phase II trial using a Simon 2-stage design. The primary endpoint was objective tumor response (OR) plus stable disease ≥4 months (SD4) rate; if ≥8 patients had OR+SD4, the study would proceed to stage 2. Results: Thirteen patients were enrolled into the phase I portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in combination with gemcitabine. Twenty-one additional patients were then enrolled at the RP2D (phase II). Of the 22 response evaluable patients treated at the RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%) had a partial response to treatment. Objective criteria for continuing to stage 2 were thus not met and the trial was closed following the accrual of 34 patients. Conclusion: Saracatinib 175 mg daily in combination with gemcitabine is well tolerated but the combination did not improve efficacy over what would be expected from gemcitabine alone. © Springer Science+Business Media, LLC 2010.

Nichols C.,Virginia Mason Medical Center | Kollmannsberger C.,British Columbia Cancer Agency Vancouver Cancer Center
Hematology/Oncology Clinics of North America | Year: 2011

The development of effective chemotherapy has been the defining event in the history of testicular cancer treatment. The discovery of cisplatin-based chemotherapy created a massive inflection that sharply defined the relatively grim precisplatin era from the astonishing postcisplatin era. The ripple effects of this discovery continue today with the rewriting of management of early-stage germ cell tumors to surveillance-based programs. This article reviews the discovery, development, and delivery of cisplatin-based chemotherapy; expected outcomes of chemotherapy treatment; remaining controversies in primary chemotherapy treatment of disseminated disease; and practical management tips for delivery of bleomycin, etoposide, and cisplatin and after chemotherapy treatment. © 2011 Elsevier Inc.

Halabi S.,Duke University | Kelly W.K.,Thomas Jefferson University | Ma H.,Duke University | Solomon N.C.,Duke University | And 20 more authors.
Journal of Clinical Oncology | Year: 2016

Purpose Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients.Weinvestigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials. Patients and Methods Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases. Results Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although menwith lungmetastases had bettermedian OS (19.4months) compared with menwith liver metastases, they had significantly worse median survival duration than men with nonvisceral bone metastases (21.3 months). Men with LN-only disease had a median OS of 31.6 months. The pooled hazard ratios for death in men with lung metastases compared with men with bone with or without LN metastases and in men with any liver metastases compared withmen with lung metastases were 1.14 (95% CI, 1.04 to 1.25; P = .007) and 1.52 (95% CI, 1.35 to 1.73; P , .0001), respectively. Conclusion Specific sites of metastases in men with mCRPC are associated with differential OS, with successive increased lethality for lung and liver metastases compared with bone and nonvisceral involvement. These data may help in treatment decisions, the design of future clinical trials, and understanding the variation in biology of different sites of metastases in men with mCRPC.A. ©2016 by American Society of Clinical Oncology.

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