A multi-institution phase II study of gemcitabine/cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002).

[Purpose]Gemcitabine/cisplatin combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). We aimed to evaluate the efficacy and safety of adding S-1 to gemcitabine/cisplatin combination therapy for patients with advanced BTC. [Methods]Patients with histologically or cytologically confirmed unresectable or recurrent BTC were eligible for inclusion. The primary end point was overall survival. Based on the results of our preceding phase I study, gemcitabine and cisplatin were administered intravenously at doses of 1, 000 or 25 mg/m2, respectively, on day 1, and oral S-1 was administered daily at a dose of 80 mg/m2 on days 1–7 every 2 weeks. This study was registered with ClinicalTrials.gov (NCT01284413) and the UMIN Clinical Trials Registry (ID 000004468). [Results]Fifty patients enrolled between October 2011 and August 2012 were evaluated. After a median follow-up of 15.1 months (range 2.4–24.4 months), the median overall survival time was 16.2 months [95 % confidence interval (CI) 10.2–22.2 months], and the one-year overall survival rate was 59.9 % (95 % CI 46.2–73.5 %). The grade 3–4 hematological toxicities were as follows: neutropenia (32 %), anemia (32 %), thrombocytopenia (10 %), and febrile neutropenia (4 %). The common grade 3–4 non-hematological toxicities were biliary tract infection (14 %), anorexia/nausea (10 %), and fatigue (8 %). [Conclusions]Gemcitabine/cisplatin/S-1 combination chemotherapy offered a promising survival benefit with manageable toxicity in patients with advanced BTC. A randomized phase III trial to investigate the efficacy of this regimen compared to gemcitabine/cisplatin combination therapy in patients with advanced BTC is now underway (UMIN000014371/NCT02182778)