A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC)

• Published in: Annals of oncology Vol. 27; no. 7; pp. 1266 - 1272
• Main Authors: Oki, E., Murata, A., Yoshida, K., Maeda, K., Ikejiri, K., Munemoto, Y., Sasaki, K., Matsuda, C., Kotake, M., Suenaga, T., Matsuda, H., Emi, Y., Kakeji, Y., Baba, H., Hamada, C., Saji, S., Maehara, Y.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2016; Oxford University Press
• Subjects: adjuvant chemotherapy; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Chemotherapy, Adjuvant - adverse effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Disease-Free Survival; Drug Combinations; Drug-Related Side Effects and Adverse Reactions - pathology; Female; Humans; Japan; local recurrence; Male; Middle Aged; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Original; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; rectal cancer; Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; S-1; Tegafur - administration & dosage; Tegafur - adverse effects; total mesorectal excision; UFT; Uracil - administration & dosage; Uracil - adverse effects; adjuvant chemotherapy; UFT; local recurrence; S-1; rectal cancer; total mesorectal excision
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdw162

Preventing distant recurrence and achieving local control 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. 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 (500–600mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. 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% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63–0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. 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.