A phase II trial of biweekly high dose gemcitabine for patients with metastatic pancreatic adenocarcinoma

BACKGROUND, Although the novel cytidine analog gemcitabine has shown superior antiturnor activity compared with weekly bolus 5-fluorouracil in patients with advanced pancreatic carcinoma, further improvements of therapeutic results are warranted. The current Phase II study was initiated to investigate whether this might be achieved by dose intensification. METHODS, Between August 1997 and September 1998, 43 consecutive patients with metastatic pancreatic adenocarcinoma were enrolled in this multicenter Phase II trial. Patients received 4 weekly courses of gemcitabine 2200 mg/m(2) given as intravenous infusion during 30 minutes on Days 1 and 15 for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of treatment was assessed according to standard criteria, i.e., objective response, progression free survival, and overall survival, as well as by analysis of clinical benefit response (defined as greater than or equal to 50% reduction in pain intensity, greater than or equal to 50%, reduction in daily analgesic consumption, and/or greater than or equal to 20 point improvement in Karnofsky performance status that was sustained for greater than or equal to 4 consecutive weeks). RESULTS. Of 43 patients evaluable for objective response, 1 achieved complete and 8 partial remissions, for an overall response rate of 21% (95% confidence interval, 10-36%); 18 additional patients (42%) had stable and 16 (37%) progressive disease. The median time to progression was 5.3 months. Median survival was 8.8 months, and the probability of surviving beyond 12 months was 26.3%. Of 36 patients with rumor-related symptoms who were considered evaluable for clinical benefit response, 16 (44%) experienced significant palliation. The median time to achieve a clinical benefit response was 6 weeks, and its median duration was 27 weeks. Chemotherapy was well tolerated, with leukopenia/graulocytopenia representing the most common side effect. Gastrointestinal and other subjective toxicities were infrequent and generally mild. CONCLUSIONS, Biweekly high dose gemcitabine seems to represent a safe, tolerable, and effective regimen for the palliative treatment of patients with advanced pancreatic carcinoma. (C) 2000 American Cancer Society.