title: A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC).
abstract: 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 (500-600 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 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.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka okieiji@surg2.med.kyushu-u.ac.jp.
authors.forename: E
authors.initials: E
authors.lastname: Oki
authors.affiliation: Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Aomori.
authors.forename: A
authors.initials: A
authors.lastname: Murata
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu.
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka.
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Surgery, Gastrointestinal Center, National Hospital Organization Kyushu Medical Center, Fukuoka.
authors.forename: K
authors.initials: K
authors.lastname: Ikejiri
authors.affiliation: Department of Surgery, Fukui-ken Saiseikai Hospital, Fukui.
authors.forename: Y
authors.initials: Y
authors.lastname: Munemoto
authors.affiliation: Department of Surgery, Otaru Ekisaikai Hospital, Hokkaido.
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, Osaka General Medical Center, Osaka.
authors.forename: C
authors.initials: C
authors.lastname: Matsuda
authors.affiliation: Department of Surgery, Kouseiren Takaoka Hospital, Toyama.
authors.forename: M
authors.initials: M
authors.lastname: Kotake
authors.affiliation: Gastroenterological Surgery, Nanpuh Hospital, Kagoshima.
authors.forename: T
authors.initials: T
authors.lastname: Suenaga
authors.affiliation: Department of Surgery, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima.
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka.
authors.forename: Y
authors.initials: Y
authors.lastname: Emi
authors.affiliation: Devision of Gastrointestinal Surgery, Kobe University Hospital, Kobe.
authors.forename: Y
authors.initials: Y
authors.lastname: Kakeji
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto.
authors.forename: H
authors.initials: H
authors.lastname: Baba
authors.affiliation: Faculty of Engineering, Tokyo University of Science, Tokyo.
authors.forename: C
authors.initials: C
authors.lastname: Hamada
authors.affiliation: Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Saji
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: Y
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D014498:Uracil; D010094:Oxonic Acid
keywords: S-1; UFT; adjuvant chemotherapy; local recurrence; rectal cancer; total mesorectal excision