Phase II study of gemcitabine and cisplatin in the treatment of patients with advanced pancreatic carcinoma

Background. Pancreatic carcinoma is considered among the most chemoresistan t of human malignancies. The most commonly used cytotoxic single agents, 5- fluorouracil and 2'-deoxy-2',2'-difluorocytidine (gemcitabine), have object ive response rates of less than 10% in large studies. Hypothesizing noncros s resistance and a synergistic interaction between geracitabine and cisplat in, early clinical studies have demonstrated significant activity with this combination in patients with several types of malignant disease. A Phase I I study was under-taken to determine the efficacy of gemcitabine in combina tion with cisplatin in patients with locally advanced and metastatic pancre atic carcinoma based on these considerations. Methods. The eligibility criteria included histologically confirmed, locall y advanced, unresectable or metastatic exocrine carcinoma of the pancreas w ith no prior gemcitabine therapy; prior adjuvant therapy was allowed provid ed the last day of therapy was at least 6 months prior to starting treatmen t; clinically measurable or evaluable disease; a Southwest Oncology Group s cale performance status of 0-2; a life expectancy of > 12 weeks; and adequa te bone marrow, hepatic, and renal function. A total of 42 patients, 4 pati ents with locally advanced, unresectable disease and 38 patients with metas tatic disease, were treated and received a total of 211 cycles of therapy b etween May 1997 to March 1999. The median age of patients was 61.5 years. T he patients were treated in the outpatient setting with a combination of ge mcitabine 1,000 mg/M-2 intravenously over 30 minutes administered on Days 1 , 8, and 15 of each cycle and cisplatin 50 mg/M-2 intravenously administere d after gemcitabine infusion on Days 1 and 15 with adequate prehydration ac companied by adequate urinary output. Cycles were repeated every 28 days. R esponse and toxicity were assessed according to World Health Organization a nd standard criteria. Results. The complete and partial response rate among all 42 registered pat ients was 11 of 42 patients (26%; 95% confidence interval, 0.14-0.42). Stab ilization of disease was seen in 15 patients (38%). Two additional patients with metastatic disease who achieved major responses to chemotherapy were rendered free of disease surgically, achieving a complete response status. The median overall survival was 7.1 months (95% confidence interval [CI], 6 .3-9.1 months), with 64% of patients alive at 6 months and 19% of patients alive at 12 months. The median time to disease progression was 5.4 months ( range, 0.9-20.8 months). Major toxicities were neutropenia and thrombocytop enia, with one episode of neutropenic fever. Conclusions, The combination of gemcitabine and cisplatin appeared to have significantly greater activity than single-agent gemcitabine in this Phase II study, with tolerable toxicity. The antitumor activity of this combinati on needs to be confirmed in multi-institutional or comparative trials. Canc er 2001;92:569-77. (C) 2001 American Cancer Society.