A phase II study of uracil-tegafur plus doxorubicin and prognostic factors in patients with unresectable biliary tract cancer

The purpose of this study was to clarify the safety and efficacy of combination chemotherapy of uracil-tegafur (UFT) and doxorubicin (UFD regimen), and to identify the prognostic factors in patients with unresectable advanced biliary tract cancer who received systemic chemotherapy. Patients with histologically or cytologically confirmed, measurable biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer, who were not suitable candidates for surgery, were eligible for the study. Patients received oral UFT at 300 mg/m(2) per day divided into two doses on days 1-14 and intravenous doxorubicin at 30 mg/m(2) on day 1. This cycle was repeated every 21 days. The relationship between the patient characteristics and the prognosis was examined. Univariate and multivariate analyses were conducted to identify the prognostic factors associated with survival. Sixty-one patients from 12 institutions were enrolled in the late phase II study between April 2005 and March 2006. Of the 61 patients, 4 patients had partial responses, for an objective response rate of 6.6% (95% CI: 1.8-15.9%); 28 patients had stable disease, 27 had progressive diseases, and 2 patients were not evaluated. The median progression-free survival was 1.6 months, and the overall median survival time was 6.5 months. In the 85 patients who received this UFD chemotherapy in previous and late phase II studies, multivariate analysis revealed the ECOG performance status 1 (P = 0.001), gallbladder as the primary cancer site (P = 0.014), T-factor 4 of the TNM classification (P = 0.035), and elevated serum lactate dehydrogenase levels (P = 0.043) as being associated with a significantly shorter survival. Combination chemotherapy of UFT and doxorubicin had minimum activity against advanced biliary tract cancer. Performance status was identified as the most important prognostic factor in patients who received systemic chemotherapy.