Phase 2 Trial of Adjuvant Chemotherapy With S − 1 for Node-Positive Biliary Tract Cancer (N-SOG 09)

BACKGROUND: Nodal metastasis is a leading attributable factor of poor survival in biliary tract cancer (BTC), and adjuvant chemotherapy targeting this high-risk feature has not been attempted to date. This study aimed to test the efficacy of adjuvant S - 1 for patients with node-positive BTC. METHODS: This single-arm multicenter phase 2 trial enrolled patients who underwent resection for histologically proven node-positive BTC. In this trial, S - 1 was administered at a dose of 80-120 mg/day on 14 days of a tri-weekly cycle for 6 months. The primary end point of the trial was 3-year overall survival (OS), in which the result would be promising if the 90% confidence interval (CI) surpassed a threshold of 30% (alpha error, 0.1; beta error, 0.2). The secondary end points were relapse-free survival (RFS), feasibility, and toxicity. RESULTS: The trial included 50 patients with perihilar (n = 23) or distal (n = 20) cholangiocarcinoma, or gallbladder cancer (n = 7). The median numbers of positive lymph nodes and examined lymph nodes were respectively 2 and 15. The 3-year OS and RFS were respectively 50% (90% CI, 40.9-59.1%) and 32.0% (95% CI, 19.1-44.9%), with median survival times of 34.6 months (95% CI, 19.3-49.8 months) and 18.4 months (95% CI, 11.9-24.9 months). Although hematologic toxicity often occurred, grades 3 and 4 toxicity were rare. The completion rate of the test therapy was 64%, and the median relative dose intensity was 87.5% (interquartile range, 50-100%). CONCLUSION: Adjuvant chemotherapy with S - 1 may be promising for patients with node-positive BTC.