Phase II study of paclitaxel therapy for unresectable biliary tree carcinomas

Purpose: To evaluate the efficacy of paclitaxel administered to patients with unresectable adenocarcinomas of the gallbladder and biliary tree over 3 hours every 21 days. Patients and Methods: Fifteen patients with unresectable and/or metastatic carcinoma of the gallbladder and bile ducts received intravenous paclitaxel over 3 hours after premedication with dexamethasone, diphenhydramine, and cimetidine. Treatment was repeated every 21 days, and one complete course of therapy was comprised of two such 21- day treatment cycles. The initial dose of paclitaxel was 170 mg/m², and this was elevated to 200 mg/m² due to tolerance within the initial patient cohort. Results: All patients were assessable for both toxicity and response: 11 with bile duct cancer and four with gallbladder carcinoma. Forty-three cycles of therapy were delivered during the trial (median, two), and one patient remains on treatment. No complete or partial responses were noted, although two patients achieved minor responses that lasted 2 and 2+ months, respectively. There were no deaths on this study, and all but one of the patients is still alive. The therapy was well tolerated, and hematologic and mucosal toxic effects were moderate and readily reversible, although significant neuromuscular adverse effects were noted. Conclusion: These findings indicate that paclitaxel administered on this schedule, is tolerable, but is unlikely to have activity in metastatic carcinomas of the biliary tree. It is unclear whether a different regimen of paclitaxel, or another taxane, may have activity in these neoplasms.