Adjuvant S-1 Therapy After Resection of Biliary Cancer

After resection of biliary cancer, standard adjuvant therapy is 6 months of postoperative capecitabine. Investigators now report results of a trial evaluating adjuvant therapy with the oral agent S-1, which combines the fluorinated pyrimidine tegafur with gimeracil, a dihydropyrimidine dehydrogenase inhibitor to enhance absorption, and oteracil to reduce bowel toxicity.

In this multicenter, open-label, phase 3 trial, 440 patients in Japan with resected biliary cancer were randomized to either observation or treatment with S-1 dosed at 40, 50, or 60 mg, depending on body surface area, and given twice daily for 4 weeks followed by a 2-week rest period for 4 cycles. Median age was 69 and most patients (71%) were male. Most (56%) had extrahepatic primary tumors, followed by ampullary, gallbladder, and intrahepatic. The majority of tumors were stage T2 (58%), were node negative (60%), and had clear margin R0 resection (85%). Half of patients required pancreatoduodenectomy with or without hepatectomy.

At a median follow up of 45.4 months, the primary endpoint of 3-year overall survival was significantly improved with S-1compared with observation (77.1% vs. 67.6%; hazard ratio, 0.69; one sided P = 0.0080). Three-year relapse-free survival trended better with S-1 compared with observation (62.4% vs. 50.9%; HR, 0.80; two-sided P = 0.088). No new safety signals were observed. Prespecified subset analyses indicated the greatest benefit in females, in N1 disease, and after R0 resection.