Long-term Efficacy of S-1 Monotherapy or Capecitabine Plus Oxaliplatin as Adjuvant Chemotherapy for Patients with Stage II or III Gastric Cancer after Curative Gastrectomy: a Propensity Score-Matched Multicenter Cohort Study

Abstract

Purpose: To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC).

Materials and methods: This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively.

Results: The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693-4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664-1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595-85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502-5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618-3.028; P<0.001) were determined as independent prognostic factors for DFS.

Conclusions: S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.

Keywords: Adjuvant chemotherapy; Disease-free survival; Gastric cancer.

Fig. 1. Flowchart of PSM.

CAPOX = capecitabine and oxaliplatin; S-1 = tegafur/gimeracil/oteracil; BMI = body mass index; ASA = American Society of Anesthesiologists; OP = operation; AJCC = American Joint Committee on Cancer; PSM = propensity score matching.

Fig. 2. DFS of patients with stage II and III gastric cancer according to adjuvant chemotherapy regimen; (A) stage II, (B) stage IIA, (C) stage IIB, (D) stage III, (E) stage IIIA, (F) stage IIIB, and (G) stage IIIC.

CAPOX = capecitabine and oxaliplatin; S-1 = tegafur/gimeracil/oteracil; DFS = disease-free survival.

Fig. 3. Forest plot for subgroup analysis of disease-free survivals in S-1 and CAPOX groups.

CAPOX = capecitabine and oxaliplatin; S-1 = tegafur/gimeracil/oteracil; HR = hazard ratio; CI = confidence interval; ASA = American Society of Anesthesiologist; AJCC 8th, 8th edition of American Joint Committee on Cancer.