Two consecutive phase II studies of 5-fluorouracil/leucovorin/mitomycin C and of gemcitabine in patients with advanced biliary cancer.

Carcinoma of the biliary system is a rare tumor entity, and patients with advanced disease face a dismal prognosis. Because of the absence of standard chemotherapy for advanced biliary carcinoma, we have performed two consecutive studies to evaluate the clinical potential of 5-fluorouracil, leucovorin and mitomycin C as well as the novel antimetabolite gemcitabine in this disease. A total of 39 consecutive patients suffering from locally inoperable or metastatic biliary cancer were enrolled in the study between March 1994 and October 1997. Twenty patients were treated with leucovorin 200 mg/m2 and 5-FU 400 mg/m2, both given as intravenous bolus on days 1-4, and mitomycin C 8 mg/m2 on day 1 (group A). Treatment cycles were repeated every 28 days. The second cohort included 19 patients, who received gemcitabine 1200 mg/m2 on days 1, 8 and 15 with a 2-week interval before the next treatment cycle (group B). Treatment was continued for a maximum of 6 cycles in the absence of progressive disease in both groups, and endpoints of the study were responses rates, survival and toxicity. In group A, 5 patients (25%) had a partial response (PR), 6 additional patients (30%) had stable disease (SD) and 9 patients (45%) progressed during treatment. The median survival was 9.5 months (range, 3-14.5) with the median time to progression being 4 months (range, 3-9). In group B, 3 patients achieved a PR (16%), 4 showed SD (21%), while the remaining 12 patients had progressive disease. A median survival of 6.5 months (range, 2-11.5) was obtained, and the median time to progression was 2.5 months (range, 1-6+). Toxicity was generally mild in both treatment arms, 6 patients in group A required dose reductions, while no dose adaptation had to be performed for gemcitabine. Our data suggest that treatment of advanced biliary cancer is feasible and can be safely performed with both regimens applied in our study. While administration of gemcitabine has resulted in only mild toxicities, its exact impact on the management of advanced biliary cancer should be evaluated in a controlled trial.