Abstract
OBJECTIVE: To evaluate efficacy of S-1 (tegafur/gimeracil/oteracil), an active novel fluoropyrimidine, as compared to UFT (tegafur/uracil) as a postoperative adjuvant therapy in patients with node-negative non-small cell lung cancer (NSCLC). METHODS: Eligible patients had undergone complete resection of p-stage I (T1 with tumor diameter >2 cm or T2-N0M0 by 5th edition Union for International Cancer Control TNM) NSCLC, and were randomized to receive oral UFT 250 mg/m(2)/day for 2 years (Arm A) or oral S-1 80 mg/m(2)/day for 2 weeks with a 1-week rest period, for 1 year (Arm B). The primary end point was relapse-free survival (RFS), with 80% power and a one-sided type I error of 0.05. RESULTS: From November 2008 to December 2013, 963 patients were enrolled (Arm A: 482, Arm B: 481). Toxicities (hematologic/nonhematologic) of grade 3 or more were observed in 15.9 (1.5/14.7)% in Arm A, and in 14.9 (3.6/12.1)% in Arm B, respectively. At data cut-off in December 2018, the hazard ratio for RFS was 1.06 (95% confidence interval, 0.82-1.36), showing no superiority of S-1 over UFT. The hazard ratio of overall survival (OS) was 1.10 (95% confidence interval, 0.81-1.50). The 5-year RFS/OS were 79.4%/88.8% in Arm A and 79.5%/89.7% in Arm B, respectively. The original NSCLC accounted for 58%/53%, respectively, of the Arm A/Arm B OS events. Secondary malignancies were observed in 85 (17.8%) and 84 (17.8%) individuals in Arm A and Arm B, respectively. CONCLUSIONS: S-1 was not superior to UFT as postoperative adjuvant therapy in node-negative NSCLC. Future investigation should incorporate identification of high-risk populations for recurrence.