Phase I study of daily S-1 combined with weekly irinotecan in patients with advanced non-small cell lung cancer

Int J Clin Oncol. 2009 Feb;14(1):43-7. doi: 10.1007/s10147-008-0796-9. Epub 2009 Feb 20.

Abstract

Background: S-1 is a novel oral fluorouracil prodrug active against non-small cell lung cancer (NSCLC). To determine the feasibility of S-1 combined with weekly irinotecan for patients with advanced NSCLC, we performed a phase I study to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan.

Methods: Patients with advanced NSCLC received S-1 (80 mg/m(2)) on days 1-14 and irinotecan (50-80 mg/m(2)) on days 1, 8, and 15 of each 28-day cycle. Three to six patients were treated with each dose of irinotecan, with the MTD defined as the dose at which dose-limiting toxicity (DLT) appeared in 33% of patients.

Results: At doses of 50-70 mg/m(2), no patients experienced any DLT, whereas, at a dose of 80 mg/m(2), two of four patients experienced DLTs. Two patients experienced grade 3 toxicities - neutropenia and diarrhea.

Conclusion: The MTD of weekly irinotecan was 80 mg/m(2), making its RD for phase II trials 70 mg/m(2).

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Administration Schedule
  • Drug Combinations
  • Feasibility Studies
  • Female
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Oxonic Acid / administration & dosage
  • Tegafur / administration & dosage
  • Treatment Outcome

Substances

  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Irinotecan
  • Camptothecin