A dose-escalation study of irinotecan (CPT-11) in combination with gemcitabine in patients with advanced non-small cell lung cancer previously treated with a cisplatin-based front line chemotherapy

Anticancer Res. 2002 May-Jun;22(3):1891-6.


Purpose: CPT-11 and gemcitabine are both active agents against non-small cell lung cancer (NSCLC). We conducted a phase I study to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of their combination in patients with previously treated advanced NSCLC.

Patients and methods: Twenty-seven patients with histologically confirmed NSCLC, who had failed cisplatin-based front-line chemotherapy, were enrolled. The patients' median age was 56 years, 24 were male and 22 had a performance status (WHO) 0-1. Gemcitabine was administered on days 1 and 8, as a 30-minute i.v. infusion, at escalated doses ranging from 900 to 1200 mg/m2. CPT-11 was given over a 60-minute i.v. infusion on day 8 at escalated doses ranging from 200 to 350 mg/m2, following gemcitabine administration. The treatment was repeated every three weeks.

Results: The MTD was exceeded at dose-level 7 with CPT-11 350 mg/m2 and gemcitabine 1200 mg/m2, where all three enrolled patients presented DLTs (one patient grade 4 thrombocytopenia, one grade 3 diarrhea and one grade 3 asthenia). The recommended doses for future phase II studies are CPT-11 300 mg/m2 on day 8 and gemcitabine 1200 mg/m2 on days 1 and 8. A total of 107 treatment cycles were administered. Grade 3/4 neutropenia was observed in 13 (13%) cycles, febrile neutropenia in 3 (3%) and grade 3/4 thrombocytopenia in 2 (2%). Grade 2/3 diarrhea was seen in 6 (6%) cycles, grade 2/3 nausea and vomiting in 13 (13%) and grade 2/3 asthenia in 8 (8%). Other toxicities were mild. Among 23 patients evaluable for response, PR was achieved in one (4.5%), SD in 12 (52.5%) and PD in 10 (43%).

Conclusion: The results of this phase I study clearly demonstrate that gemcitabine and CPT-11 can be efficiently combined in a low-toxicity regimen with doses equal or near monotherapy levels. Further studies are needed to evaluate the efficacy of this combination in both chemotherapy-naive and pre-treated patients with advanced NSCLC.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Female
  • Gemcitabine
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged


  • Deoxycytidine
  • Irinotecan
  • Cisplatin
  • Camptothecin
  • Gemcitabine