Phase II study of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer.

Abstract

A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC). Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m(2) intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m(2) oral S-1 on days 1-14 of each cycle. The treatment was repeated every 3 weeks. Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6%), intrahepatic and extrahepatic bile ducts in 23 (60.5%), and the ampulla of Vater in 3 (7.9%) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6% (95% CI 8.5-36.7] in the per-protocol (PP) population, and 18.4% (95%CI 6.1-30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5% (95%CI 60.6-87.6) in the PP population. The median progression-free survival was 4.4 months (95%CI 1.8-6.9), and the median overall survival was 9.0 months (95%CI 4.0-13.9) with a 1-year survival rate of 44.7% (95%CI 29.0-61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1%), 9 (25.7%), 2 (5.7%), and 2 (5.7%) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4%), anorexia (2.9%), and renal toxicity (2.9%). Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.