A phase I study of S-1 and irinotecan combination therapy in previously treated advanced non-small cell lung cancer patients

Cancer Chemother Pharmacol. 2011 Mar;67(3):717-22. doi: 10.1007/s00280-010-1539-y. Epub 2010 Dec 9.

Abstract

Background: This phase I study was conducted to evaluate the feasibility and to determine the recommended doses of the combination therapy of S-1 and irinotecan (CPT-11) in patients with advanced non-small cell lung cancer (NSCLC) as second-line treatment.

Methods: Patients with NSCLC who were previously treated with one chemotherapy regimen and had a performance status of 0 or 1 were eligible. CPT-11 was administered at 60 mg/m² (level 1), 80 mg/m² (level 2) on days 1 and 8, and oral S-1 was administered at 80 mg/day for body surface area (BSA) less than 1.25 m², 100 mg/day for BSA 1.25-1.5 m², and 120 mg/day for BSA more than 1.5 m² on days 1-14 every 3 weeks. The dose-limiting toxicity (DLT) was defined as grade 4 leukocytopenia or neutropenia, grade ≥ 3 neutropenia with fever over 38°C, grade ≥ 3 thrombocytopenia, or grade ≥ 3 major nonhematological toxicities.

Results: Nine patients were enrolled in the study. None of 3 patients enrolled in level 1 had any DLT. Of 6 patients in level 2, 2 patients had grade 3 diarrhea and one had grade 3 interstitial pneumonia. Level 1 was declared as the recommended dose.

Conclusion: The feasibility of the combination therapy of S-1 and CPT-11 was shown in the second-line setting for the treatment of advanced NSCLC. The recommended dose of CPT-11 was 60 mg/m² combined with standard dose of S-1 for phase II trials of pretreated advanced NSCLC patients.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • 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
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Tegafur / administration & dosage

Substances

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