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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.

Journal of thoracic disease 2025 Vol.17(11) p. 10209-10219

Fujino K, Maruyama R, Marutsuka T, Iwatani K, Aoki M, Suetsugu T, Takenaka M, Saeki S, Sakata S, Motooka Y, Masuda Y, Yoshimoto K, Ikeda K, Suzuki M

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[BACKGROUND] Platinum-based doublet chemotherapy is recommended as the standard adjuvant treatment for completely resected stage II/III non-small cell lung cancer (NSCLC).

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APA Fujino K, Maruyama R, et al. (2025). 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.. Journal of thoracic disease, 17(11), 10209-10219. https://doi.org/10.21037/jtd-2025-1518
MLA Fujino K, et al.. "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.." Journal of thoracic disease, vol. 17, no. 11, 2025, pp. 10209-10219.
PMID 41376950

Abstract

[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.

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