Randomized phase II trial of S-1 and cisplatin versus gemcitabine and cisplatin in advanced biliary tract adenocarcinoma.

Abstract

4029 Background: Gemcitabine plus a platinum has been reported to be the most effective treatment against advanced biliary tract adenocarcinoma (ABTA). S-1 has also shown potent antitumor activity as monotherapy or in combination with platinum. The aim of this study was to evaluate the efficacy and safety of combination chemotherapy with S-1 and cisplatin (SP) versus gemcitabine and cisplatin (GP) as first-line therapy in ABTA. Methods: Patients with ABTA including gallbladder cancer, intrahepatic cholangiocarcinoma (IHCCC), extrahepatic bile duct carcinoma, and ampulla of Vater cancer were randomized to receive either S-1 (40 mg/m2 bid orally D1-14) and cisplatin (60 mg/m2 IV D1) or gemcitabine (1,000 mg/m2 IV fixed dose rate of 10 mg/m2/min on D1,8) and cisplatin (60 mg/m2 IV on D1). Cycles were repeated every 3 weeks. The primary end point was 6-month progression-free survival (PFS) and randomized phase II trial design was used to select the better regimen for further investigation. Secondary endpoints was the response rate (RR) and overall survival (OS). Results: Between March 2008 and March 2009, a total of 96 eligible patients (SP = 47, GP = 49) were enrolled. Overall response rates for patients assigned to GP and SP were 18.4% (95% CI 7.5-29.2%) and 21.3% (95% CI, 9.6-33%, p = 0.721), respectively. With a median follow-up duration of 14.1 months for all patients (95% CI, 12.7-15.5 months), 6-months PFS was 44.0% in GP and 35.3% in SP [unadjusted HR (GP/SP) = 0.85, 95% CI, 0.52-1.36, p = 0.488]. The median OS and estimated 1-year survival rate were 10.1 months and 42.2% in GP and 9.9 months and 21.9% in SP (unadjusted HR [GP/SP] = 0.72, 95% CI = 0.45-1.17, p = 0.187). Grade 3 to 4 toxicities for SP vs. GP were: neutropenia (31.8% vs. 49%), anemia (2.3% vs. 22.4%), thrombocytopenia (4.5% vs. 22.4%), asthenia (2.1% vs. 4.1%), and diarrhea (4.3% vs. 0%). Febrile neutropenia developed only in GP arm (4.1%). Conclusions: Despite of more frequent hematologic toxicities and inconvenience associated weekly visit, GP showed better 6-months PFS and OS based on statistical design, gemcitabine in combination with cisplatin was selected over SP for further investigation in ABTA. No significant financial relationships to disclose.