title: Optimal schedule of adjuvant chemotherapy with S-1 for stage III colon cancer: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Although, in Western countries, oxaliplatin-based regimens have been established as a gold standard treatment for patients with stage III or high risk stage II colon cancer after curative resection, in Japan fluorouracil-based regimens have been widely accepted and recommended in the guidelines for adjuvant settings in patients with stage III colon cancer. S-1, an oral preparation evolved from uracil and tegafur, has equivalent efficacy to uracil and tegafur/leucovorin for treating patients with advanced colorectal cancer and might be a suitable regimen in an adjuvant setting. However, the completion rate of the standard six-week cycle of the S-1 regimen is poor and the establishment of an optimal treatment schedule is critical. Therefore, we will conduct a multicenter randomized phase II trial to compare six-week and three-week cycles to establish the optimal schedule of S-1 adjuvant therapy for patients with stage III colon cancer after curative resection.
  
  
  METHODS
  The study is an open-label, multicenter randomized phase II trial. The primary endpoint of this study is three-year disease-free survival rate. Secondary endpoints are the completion rate of the treatment, relative dose intensity, overall survival, disease-free survival, and incidence of adverse events. The sample size was 200, determined with a significance level of 0.20, power of 0.80, and non-inferiority margin of a 10% absolute difference in the primary endpoint.
  
  
  CONCLUSIONS
  Although S-1 has not been approved yet as a standard treatment of colon cancer in an adjuvant setting, it is a promising option. Moreover, in Japan S-1 is a standard treatment for patients with stage II/III gastric cancer after curative resection and a promising option for patients with colorectal liver metastases in an adjuvant setting. However, a six-week cycle of treatment is not considered to be the best schedule, and some clinicians use a modified schedule, such as a three-week cycle to keep a sufficient dose intensity with few adverse events. Therefore, it will be useful to determine whether a three-week cycle has an equal or greater efficacy and tolerance to side-effects compared with the standard six-week cycle schedule, and thus may be the most suitable treatment schedule for S-1 treatment.
  
  
  BACKGROUND
  The University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000006750.
authors: Department of Clinical Trial Design & Management, Translational Research Center, Kyoto University Hospital, 54 Shogoin Kawahara, Sakyo, Kyoto, 606-8507, Japan. keyoshim@kuhp.kyoto-u.ac.jp
authors: Kenichi
authors: K
authors: Yoshimura
authors: Keisuke
authors: K
authors: Uehara
authors: Yuichiro
authors: Y
authors: Tojima
authors: Satoru
authors: S
authors: Kawai
authors: Yasuji
authors: Y
authors: Mokuno
authors: Atsuyuki
authors: A
authors: Maeda
authors: Takanori
authors: T
authors: Kyokane
authors: Satoshi
authors: S
authors: Kobayashi
authors: Yuichiro
authors: Y
authors: Yoshioka
authors: Masato
authors: M
authors: Nagino
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D002985:Clinical Protocols; D003082:Colectomy / Q000009:adverse effects / Q000401:mortality; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D007564:Japan; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid