A Randomized Phase III Trial Comparing S-1 Versus UFT as Adjuvant Chemotherapy for Stage II/III Rectal Cancer (JFMC35-C1: ACTS-RC)
Mené au Japon sur 961 patients atteints d'un cancer rectal de stade II/III traité par résection, cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans récidive, et la toxicité du S-1 par rapport à une chimiothérapie adjuvante de référence (tegafur/uracile)
Backgrounds Prevention of distant and local recurrence are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur–uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. Patients and Methods The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20–80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500–600 mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120 mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary endpoint was relapse-free survival (RFS), and the secondary endpoints were overall survival and adverse events. Results In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61·7% (95% CI: 57·1–65·9%) for UFT and 66·4% (95% CI: 61·9–70·5%) for S-1 (P=0·0165, HR: 0·77, 95% CI: 0·63–0·96). Five-year survival was 80·2% (95% CI: 76·3–83·5%) for UFT and 82·0% (95% CI: 78·3–85·2%) for S-1. The main grade 3 or higher adverse events were increased ALT and diarrhea (each 2·3%) in the UFT arm and anorexia, diarrhea (each 2·6%), and fatigue (2·1%) in the S-1 arm. Conclusion One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.
Annals of Oncology 2016