A Multi-institution Phase II Study of Gemcitabine/S-1 Combination Chemotherapy for Patients with Advanced Biliary Tract Cancer

Purpose: We aimed to evaluate the efficacy and safety of gemcitabine/S-1 combination chemotherapy for the treatment of patients with advanced biliary tract cancer.

Methods: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were eligible for inclusion. The primary endpoint was overall survival. Gemcitabine was administered intravenously at a dose of 1,000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 was administered daily at a dose of 60 mg/m(2) on days 1-14. This schedule was repeated every 3 weeks until disease progression or patient refusal.

Results: Twenty-five patients were enrolled between October 2007 and January 2009. Eleven patients (44%) had extrahepatic bile duct cancer, 5 (20%) had intrahepatic bile duct cancer, 8 had gallbladder cancer (32%), and 1 (4%) had ampulla of Vater cancer. The median overall survival time was 12.7 months (95% CI, 8.4-23.5 months), and the 1-year survival rate was 52.0% (95% CI, 31.2-69.2%). Of the 23 patients with evaluable target regions, seven patients experienced a partial response, and an overall response rate was 30.4%. The following grade 3-4 hematological toxicities occurred: neutropenia (56%), leukopenia (24%), anemia (8%) and thrombocytopenia (4%). In spite of the high incidence of grade 3-4 neutropenia, no patients developed febrile neutropenia in the present study. The major grade 3-4 non-hematological toxicities were fatigue (8%), anorexia (8%) and diarrhea (4%).

Conclusions: Gemcitabine/S-1 combination chemotherapy offered a promising survival benefit with acceptable toxicity in patients with advanced biliary tract cancer.