A phase I clinical trial of irinotecan and carboplatin in patients with extensive stage small cell lung cancer

Chemotherapy. 2012;58(4):257-63. doi: 10.1159/000341274. Epub 2012 Aug 15.

Abstract

Background: Treatment options for small cell lung cancer (SCLC) remain inadequate. Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain. We undertook a phase I trial to optimise the dose intensity of a 3-weekly irinotecan/carboplatin combination.

Methods: Twenty patients with extensive stage SCLC received intravenous carboplatin at an area under the curve (AUC) of 5 on day 1, and irinotecan in 40-70 mg/m2 dose levels on days 1 and 8, every 21 days, for up to 6 cycles.

Results: Dose-limiting toxicity occurred in 1 patient at the 50 mg/m2 irinotecan level (grade 3 diarrhoea) and in 2 patients at 70 mg/m2 (grade 5 neutropenic sepsis; combined grade 4 febrile neutropenia, grade 4 diarrhoea and grade 3 thrombosis). Toxicity patterns were consistent with the expected profile for this combination. The objective response rate was 75% and the median survival was 9.3 months (95% confidence interval 7.5-11.2).

Conclusion: Irinotecan 60 mg/m2 on days 1 and 8 combined with carboplatin AUC 5 every 21 days is recommended for phase II evaluation. This regimen has clinical activity, acceptable toxicity and greater dose intensity over those currently tested in phase III trials.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Area Under Curve
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use*
  • Diarrhea / etiology
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neutropenia / etiology
  • Sepsis / etiology
  • Small Cell Lung Carcinoma / drug therapy*
  • Thrombosis / etiology

Substances

  • Antineoplastic Agents
  • Irinotecan
  • Carboplatin
  • Camptothecin