Gemcitabine for the Treatment of Advanced Biliary Tract Carcinomas: Evaluation of Two Different Dose Regimens

Abstract

Background: There is no standard therapy for the treatment of patients with nonresectable biliary tract carcinomas who face a particularly dismal prognosis. In view of the urgent need to define better treatments and of the conflicting data on the therapeutic potential of gemcitabine in this disease, we have performed 2 consecutive clinical investigations using 2 different dose schedules of this novel antimetabolite. Patients and Methods: 38 patients with locally nonresectable or metastatic biliary tract cancer were enrolled in this study; 24 patients were treated with gemcitabine 1,200 mg/m² on days 1, 8, and 15 with 2 weeks rest before application of the next cycle (group A). A second cohort of 14 patients received gemcitabine at an increased dose level of 2,200 mg/m² every 2 weeks (group B). In both treatment groups, chemotherapy was to be continued for 6 months unless there was prior evidence of progressive disease. Results: In group A, 4/24 patients (17%; 95% confidence interval CI 5–37%) had a partial response (PR), 8 additional patients (33%) had stable disease (SD) and 12 patients (50%) progressed during treatment. The median survival was 6.8 (range, 2–14) months, with the median time to progression being 3.5 (range 1–10.5) months. In group B, 4/14 patients achieved a PR (29%; 95% CI 8–58%), 5 showed SD (36%), while the remaining 5 patients had progressive disease. A median survival time of 10.5 (range 3.3–16+) months was obtained, and the median time to progression was 4.8 (range, 1.8–10.5) months. Toxicity was generally mild in both treatment groups with only a few patients experiencing WHO grade 3 haematotoxicity and/or mild gastrointestinal symptoms or fatigue. Conclusions: Our data suggest that treatment of advanced biliary tract cancer with gemcitabine is feasible and can be safely performed with both dose regimens used in this study. The therapeutic results that were achieved in the second cohort of patients (group B) are encouraging, and have stimulated us to further investigate the bi-weekly high-dose gemcitabine regimen.