Gemcitabine for the treatment of advanced biliary tract carcinomas: Evaluation of two different dose regimens

Background: There is no standard therapy for the treatment of patients with nonresectable biliary tract carcinomas who face a particularly dismal prog nosis. In view of the urgent need to define better treatments and of the co nflicting 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 patie nts with locally nonresectable or metastatic biliary tract cancer were enro lled in this study; 24 patients were treated with gemcitabine 1,200 mg/m(2) on days 1, 8, and 15 with 2 weeks rest before application of the next cycl e (group A). A second cohort of 14 patients received gemcitabine at an incr eased dose level of 2,200 mg/m(2) every 2 weeks (group B). in both treatmen t groups, chemotherapy was to he continued for 6 months unless there was pr ior evidence of progressive disease. Results: In group A, 4/24 patients (17 %; 95% confidence interval CI 5-37%) had a partial response (PR), 8 additio nal patients (33%) had stable disease (SD) and 12 patients (50%) progressed during treatment. The median survival was 6.8 (range, 2-14) months, with t he 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 t he 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 progressi on was 4.8 (range, 1.8 to 10.5) months. Toxicity was generally mild in both treatment groups with only a few patients experiencing WHO grade 3 haemato toxicity and/or mild gastrointestinal symptoms or fatigue. Conclusions: Our data suggest that treatment of advanced biliary tract cancer with gemcitab ine is feasible and can be safely performed with both dose regimens used in this study. The therapeutic results that were achieved in the second cohor t of patients (group B) are encouraging, and have stimulated us to further investigate the hi-weekly high-dose gemcitabine regimen.