An open-label, multicenter, three-stage, phase II study of s-1 in combination with cisplatin as first-line therapy for patients with advanced non-small cell lung cancer.

Introduction: S-1 is a rationally designed oral agent that combines the 5-fluorouracil prodrug tegafur with gimeracil and oteracil, which inhibit 5-fluorouracil degradation by dihydropyrimidine dehydronase and phosphorylation within the gastrointestinal tract, respectively, to increase antineoplastic activity while reducing gastrointestinal toxicity. We investigated the activity and toxicity of S-1 in combination with cisplatin in patients with unresectable non-small cell lung cancer (NSCLC).

Methods: Cisplatin, 75 mg/m, was administered intravenously on day 1, with S-1, 25 mg/m PO two times a day, days 1 to 14, every 21 days for a maximum of six cycles. Primary end point was overall response.

Results: A total of 58 patients received at least one cycle of protocol-specified therapy. The best overall response rate was 23.2% (95% confidence interval: 13.0-36.4), and the disease control rate was 67.9%. The median progression-free survival was 4.0 months (95% confidence interval: 3.3-5.5). There did not appear to be any relationship between response to therapy and tumor histology. The most frequently reported adverse events of G3 or more (≥10%) were neutropenia (28%), hyponatremia (19%), diarrhea (17%), hypokalemia (12%), fatigue (10%), dehydration (10%), and deep vein thrombosis (10%).

Conclusions: Although the S-1 + cisplatin regimen used in this study appeared to have a similar level of antitumor activity and toxicity to that of established cisplatin-based doublets in NSCLC, the protocol-specified criteria of sufficient efficacy to warrant further study with an objective response rate ≥30% was not achieved. Therefore, while S-1 appears to be a promising agent in NSCLC, further evaluation should be conducted to determine the optimal S-1-based regimen to take forward for additional study.