title: Randomized phase II study of S-1 dosing schedule for resected colorectal cancer.
abstract: BACKGROUND
  Postoperative adjuvant chemotherapy for patients with stage III Colorectal cancer (CRC) is now internationally accepted as standard care for improving patient outcomes. The Adjuvant Chemotherapy Trial of S-1 for Colorectal Cancer (ACTS-CC) confirmed the non-inferiority of S-1 to tegafur/urcail/leucovorin in terms of overall survival and disease-free survival in patients with stage III CRC after curative surgery. However, the 6-month completion rate of S-1 treatment was 76.5% in the ACTS-CC. Therefore, treatment completion remains an unresolved problem.
  
  
  METHODS
  A randomized phase II trial was designed to evaluate the efficacy and safety of oral daily administration and alternate-day administration of S-1 as adjuvant chemotherapy in curatively resected stage III CRC. Enrolled patients were assigned to either S-1 daily administration (Arm A) or alternate-day S-1 administration (Arm B). Assigned treatment will start within 8 weeks after surgery. In both arms, S-1 dosing (oral) will be based on body surface area (80 mg/day for body surface area<1.25 m2, 100 mg/day for 1.25-1.5 m2, or 60 mg/day for >1.5 m2). In Arm A, S-1 will be administered orally for 28 days, followed by a 14-day rest. Administration will be conducted for 24 weeks from the date of therapy start. In Arm B, S-1 will be administered orally on alternate days for 28 weeks from the date of the start of therapy. After treatment, all patients will be observed without additional therapy unless recurrent lesions or other cancer lesions occur. The primary endpoint is treatment completion rate. Secondary endpoints include 3-year disease-free survival, compliance, and adverse events.
  
  
  CONCLUSIONS
  Previously, S-1 alternate-day intake maintained the efficacy of chemotherapy while reducing adverse effects for patients with R0-resected stage II/III gastric cancer. Improvement of chemotherapy completion rate for patients with colorectal cancer will lead to an improved patient prognosis. Therefore, a randomized phase II trial has been designed to examine the efficacy of alternate-day versus current standard daily S-1 administration as adjuvant chemotherapy for R0-resected stage III colorectal cancer.
  
  
  BACKGROUND
  This study was registered on 18 February 2014 with University Hospital Medical Information Network Clinical Trials Registry: UMIN000013185.
authors.affiliation: Department of Surgery, Osaka General Medical Center, Osaka, Japan.
authors.forename: Chu
authors.initials: C
authors.lastname: Matsuda
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan.|Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Surgery, Sakai City Hospital, Osaka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Surgery, Osaka Saiseikai Senri Hospital, Osaka, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shingai
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ikenaga
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohue
authors.affiliation: Department of Surgery, Suita Municipal Hospital, Osaka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan. hyamamoto@gesurg.med.osaka-u.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Sekimoto
authors.affiliation: Department of Surgery, Nishinomiya Municipal Central Hospital, Hyogo, Japan.
authors.forename: Riichiro
authors.initials: R
authors.lastname: Nezu
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka, 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001830:Body Surface Area; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D054796:Drug Dosage Calculations; D006801:Humans; D055118:Medication Adherence; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D012107:Research Design; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid