A phase I study for adjuvant chemotherapy of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1202)

Purpose To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy. Methods A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m 2 ) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1–14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level − 1), and 800/50 (Level − 2). Results Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level − 1. Five of 12 patients developed Grade 4 neutropenia at Level − 1 and the dose was de-escalated to Level − 2. One patient developed Grade 4 neutropenia at Level − 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level − 2. Level − 1 was confirmed as the maximum tolerated dose and Level − 2 the RD for this regimen. The 1- and 2-year recurrence-free survival rates were 77.0 and 54.0%, respectively. The recurrence-free survival rate of patients in the GS completion group was significantly higher than that of the GS discontinuation group. Conclusions Level − 2 was confirmed as the RD (GEM 800 mg/m 2 and S-1 50 mg/m 2 ) for GS adjuvant chemotherapy in curatively resected BTC patients without major hepatectomy.