Early phase II study of uracil-tegafur plus doxorubicin in patients with unresectable advanced biliary tract cancer

Background: Standard chemotherapy for advanced biliary tract cancer has not been established. The purpose of this study was to evaluate the efficacy and toxicity of a combination chemotherapy of uracil-tegafur (UFT) and doxorubicin in patients with unresectable advanced biliary tract cancer. Methods: Patients with histologically or cytologically confirmed, measurable biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of Vater cancer, which was not amenable to surgery, were eligible for the study. Patients received oral UFT 300 mg/m(2) per day divided into two doses on Days 1-14 and intravenous doxorubicin 30 mg/m(2) on Day 1. This cycle was repeated every 21 days. Additional courses of this regimen were given until a maximum of 15 courses, disease progression or the appearance of unacceptable toxicity. Results: Twenty-four patients from five institutions were enrolled between March 2004 and November 2004. Of the 24 patients, three had partial responses for an objective response rate of 12.5% (95% confidence interval, 2.7-32.4%), 13 patients had stable disease, 7 had progressive disease and the final patient was not evaluated. Grade 3 toxicity was observed in 5 of the 24 patients (20.8%), and these toxicities included anorexia, fatigue, anemia and neutropenia. None had grade 4 toxicity. The median progression-free and overall survival time was 2.5 and 7.6 months, respectively. Conclusions: Combination chemotherapy of UFT and doxorubicin was well tolerated and showed preliminary moderate activity against advanced biliary tract cancer. Further investigation in a late phase II study involving a large number of patients is recommended.