Phase II study of fixed dose-rate gemcitabine plus S-1 as a second-line treatment for advanced biliary tract cancer

Gemcitabine plus platinum is considered standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard second-line therapy has been established for this disease. According to reports, S-1 exerts anti-tumor effects on advanced biliary tract cancer and gemcitabine is more effective via fixed dose-rate administration. We evaluated the efficacy and safety of a combination of fixed dose-rate gemcitabine and S-1 after failure of gemcitabine or gemcitabine plus cisplatin therapy.

This single-arm phase II study (clinical trial number: UMIN000005918) set the response rate as the primary endpoint and used a MiniMax two-stage design with a null hypothesis < 7% and alternative hypothesis ≥ 25%. Thirty-five patients were needed to yield a power of 90% and α value of 0.05. Patients received gemcitabine (1000 mg/m², div, 100-min period, day 1) and S-1 (40 mg/m² twice daily, oral, days 1-7), every 2 weeks until disease progression or intolerable adverse events were observed.

Forty-one patients were enrolled, and 3 of 23 first-stage patients responded. The overall response rate was 9.8% [95% confidence interval (CI): 2.7-19.2%]. The median overall and progression-free survival were 7.0 [95% CI: 5.3-8.6] and 2.6 months (95% CI: 1.6-3.5), respectively. The most common grade 3-4 adverse events were leukopenia (19.5%), neutropenia (19.5%), anemia (14.6%), thrombocytopenia (7.3%), and anorexia (4.8%).

Second-line fixed dose-rate gemcitabine plus S-1 was not sufficiently effective and tolerable in patients with advanced biliary tract cancer refractory to gemcitabine or gemcitabine plus cisplatin.