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

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.

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1.

CONSORT diagram.

Figure 2.

Disease-free survival. (A) Disease-free survival by treatment arm. Noninferiority stratified log-rank test, P < 0.001. The hazard ratio in the S-1 group compared with the UFT/LV group was 0.85 [95% confidence interval (CI) 0.70–1.03]. The disease-free survival rate at 3 years was 75.5% (95% CI 72.2–78.4) in the S-1 group and 72.5% (95% CI 69.1–75.5) in the UFT/LV group. (B) Disease-free survival by UICC-TNM 7th stage. Disease-free survival rates at 3 years in stage IIIA, IIIB, and IIIC patients were 88.3%, 75.9%, and 60.1%, respectively, in the S-1 group, and 87.9%, 74.2%, and 46.4%, respectively, in the UFT/LV group.

Figure 3.

Subgroup analysis of disease-free survival in the S-1 group compared with the UFT/LV group. DFS, disease-free survival; HR, hazard ratio; CI, confidence interval; BMI, body mass index; CEA, carcinoembryonic antigen; pap, papillary adenocarcinoma; tub, tubular adenocarcinoma; por, poorly differentiated adenocarcinoma; muc, mucinous adenocarcinoma; sig, signet-ring cell carcinoma.