Phase 2 feasibility study of adjuvant chemotherapy with cisplatin (CDDP) and TS-1, followed by alternate-day TS-1 maintenance therapy, in patients with completely resected pathological stage II-IIIA non-small cell lung cancer.

Background: Platinum-based doublet chemotherapy is recommended as the standard adjuvant treatment for completely resected stage II/III non-small cell lung cancer (NSCLC). Among these regimens, cisplatin plus vinorelbine (CDDP + VNR) has been most frequently used in Japan and shown to improve survival, but it is associated with significant toxicity that often limits treatment completion. In contrast, TS-1, an oral fluoropyrimidine combined with CDDP, has demonstrated potential as a less toxic alternative. This phase 2 study aimed to assess the feasibility, safety, and efficacy of CDDP plus TS-1 (CDDP + TS-1) followed by TS-1 monotherapy as an adjuvant treatment for patients with completely resected stage II-III NSCLC. Methods: This prospective, multicenter, phase 2 study enrolled 59 patients with completely resected stage II-III NSCLC. Patients received three courses of CDDP + TS-1 in the induction phase, followed by one year of TS-1 monotherapy administered on alternate days. The primary endpoint was the completion rate of the full-protocol treatment, defined as completion of both CDDP + TS-1 induction and TS-1 maintenance. Secondary endpoints included the incidence of adverse events (AEs), relapse-free survival (RFS), and overall survival (OS). Results: The protocol completion rate for the induction phase (three cycles of CDDP + TS-1) was 72.8%. A total of 16 patients discontinued the protocol, with the most common reasons being grade ≥3 neutropenia (n=4), patient refusal (n=4), and other diseases (n=4). Five patients (8.5%) were unable to transition to TS-1 monotherapy because of severe hematological toxicities. Of the 41 patients who started TS-1 monotherapy, 79.1% completed treatment. Grade 3 AEs during the TS-1 monotherapy phase were limited to neutropenia in one case; however, none of the patients discontinued treatment due to AEs. Throughout the treatment regimen, there were no treatment-related deaths. The expected treatment completion rate of 60% was slightly surpassed, with a final rate of 57.6%. The 2-year survival rate was 88.1%, with a 3-year survival rate of 82.9%. The 2-year RFS rate was 67.8%, and the 3-year RFS rate was 62.5%. Conclusions: This phase 2 study suggests that adjuvant therapy with CDDP + TS-1 followed by TS-1 monotherapy administered on alternate days is a feasible and relatively well-tolerated treatment regimen for patients with completely resected stage II-III NSCLC. The completion rate of the full protocol, survival outcomes, and limited AEs support the potential use of this regimen as a viable alternative within platinum-based adjuvant chemotherapy strategies.