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

Alan Sandler, Charles Graham, Maria Baggstrom, Roy Herbst, Christopher Zergebel, Kaku Saito, Dennie Jones

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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/m2, was administered intravenously on day 1, with S-1, 25 mg/m2 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.

Original languageEnglish
Pages (from-to)1400-1406
Number of pages7
JournalJournal of Thoracic Oncology
Volume6
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Cisplatin
  • Clinical trial
  • Fluoropyrimidines
  • Lung cancer
  • Non-small cell
  • S-1

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