No adjuvant chemotherapy regimens after major hepatectomy for biliary tract cancer (BTC) have been standardized due to the frequency of adverse events. Survival benefits of adjuvant gemcitabine (GEM) or S-1 (S1) chemotherapy were investigated with the recommended dose determined in our previous clinical trial (KHBO1003), with 10% dose-limited toxicity.
We performed a phase II multicenter randomized trial. The primary end-point was 1-year recurrence-free survival (RFS), and the secondary end-points were other RFS, overall survival (OS), and others. The following 6-month adjuvant chemotherapy regimens were performed within 12 weeks after R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC: GEM (1000 mg/m2) every 2 weeks or S1 (80 mg/m2/day) for 28 days every 6 weeks. Thirty-five patients were assigned to each arm (alpha error, 10%; beta error, 20%). P values of < 0.10 were considered to indicate a statistically significant difference.
No patients were excluded for the per-protocol analysis. There were no statistically significant differences in the patient characteristics of the two arms. The 1-year RFS and the 1-year OS rates of the GEM arm were 51.4% and 80.0%, respectively, while those of the S1 arm were 62.9% and 97.1%, respectively. The 2-year RFS rate, the 1- and 2-year OS rates, and the OS curve of the S1 arm were superior to those of the GEM arm (p = 0.0894, p = 0.0242, p = 0.0679, and p = 0.0606, respectively), although the 1-year RFS rate was not significantly different (p = 0.334). With regard to the OS curve, the hazard ratio of the S1 group was 0.477 (90% confidence interval, 0.245-0.927).
The adjuvant chemotherapy with S1 may provide better survival benefits compared with that with GEM after major hepatectomy for BTC.
Clinical trial identification
NCT01815307 (March 21, 2013).
Legal entity responsible for the study
Kansai Hepato-Biliary Oncology Group.
Japan Society of Clinical Oncology Clinical research Grant Program 2012 and 2013.
I. Ikai, S. Morita: Lecture fee: Taiho Pharmaceutical Co., Eli Lilly Japan K.K. T. Ioka: Research funding, Lecture fee: Taiho Pharmaceutical Co. All other authors have declared no conflicts of interest.