Fractionated administration of irinotecan and cisplatin for treatment of lung cancer: a phase I study

Br J Cancer. 1999 Feb;79(5-6):984-90. doi: 10.1038/sj.bjc.6690157.

Abstract

A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose escalation of CPT-11 to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CPT-11 at escalated dose was feasible and could improve the treatment outcome. Twenty-four previously untreated patients with unresectable non-small-cell lung cancer (NSCLC) or extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP was fixed at 60 mg m(-2) and given by 1-h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an increase of 10 mg m(-2). The maximally tolerated dose of CPT-11 was determined as 60 mg m(-2) because grade 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limiting toxicity. The objective response rates were 76% for NSCLC and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m(-2) and 60 mg m(-2) respectively.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / pathology
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Cisplatin / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Hemoglobins / drug effects
  • Humans
  • Irinotecan
  • Leukocyte Count / drug effects
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Platelet Count / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Hemoglobins
  • Irinotecan
  • Cisplatin
  • Camptothecin