S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial)

Ann Oncol. 2014 Sep;25(9):1743-1749. doi: 10.1093/annonc/mdu232. Epub 2014 Jun 18.

Abstract

Background: S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV).

Patients and methods: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years.

Results: A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups.

Conclusion: Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer.

Clinicaltrialsgov: NCT00660894.

Keywords: S-1; UFT/LV; adjuvant chemotherapy; colon cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / mortality*
  • Disease-Free Survival
  • Drug Combinations
  • Female
  • Humans
  • Leucovorin / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*
  • Uracil / therapeutic use
  • Young Adult

Substances

  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Uracil
  • Oxonic Acid
  • Leucovorin

Supplementary concepts

  • 1-UFT protocol

Associated data

  • ClinicalTrials.gov/NCT00660894