S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized, Open-label, Multicenter, Phase III Superiority Trial

Clin Colorectal Cancer. 2020 Mar;19(1):22-31.e6. doi: 10.1016/j.clcc.2019.10.002. Epub 2019 Oct 18.

Abstract

Background: The efficacy of S-1 plus oxaliplatin (SOX) as postoperative adjuvant chemotherapy for colon cancer has not been established. This randomized phase III study was designed to verify the superiority of SOX over tegafur-uracil and leucovorin (UFT/LV) in patients with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries).

Patients and methods: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2 of S-1 on days 1-14, every 21 days, 8 cycles). The primary endpoint was disease-free survival (DFS).

Results: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the primary analysis. The 3-year DFS was 60.6% (95% confidence interval [CI], 56.0%-64.9%) in the UFT/LV group and 62.7% (95% CI, 58.1%-66.9%) in the SOX group. The stratified hazard ratio for DFS was 0.90 (95% CI, 0.74-1.09; stratified log-rank test, P = .2780). In the N2b subgroup, the 3-year DFS was 46.0% (95% CI, 37.5%-54.0%) in the UFT/LV group and 54.7% (95% CI, 45.7%-62.7%) in the SOX group (hazard ratio, 0.76; 95% CI, 0.55-1.05).

Conclusion: As postoperative adjuvant chemotherapy, SOX was not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer.

Keywords: Colorectal cancer; Fluoropyrimidine; L-OHP; SOX; UFT/LV.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Chemotherapy, Adjuvant / methods
  • Colectomy*
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Japan / epidemiology
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Staging
  • Oxaliplatin / administration & dosage
  • Oxonic Acid / administration & dosage
  • Tegafur / administration & dosage

Substances

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