Randomized Phase II Study of Adjuvant Chemotherapy with Long-term S-1 Versus Cisplatin+S-1 in Completely Resected Stage II–IIIA Non–Small Cell Lung Cancer

Purpose: The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non–small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome. Experimental Design: A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m2 twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m2) on day 1 plus oral S-1 (40 mg/m2 twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity. Results: The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3–74.0%) in the S group and 58.1% (95% CI, 47.7–67.2%) in the CS group. The only gene with interaction of P < 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine. Conclusions: Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy. Clin Cancer Res; 21(23); 5245–52. ©2015 AACR.