Phase I and pharmacokinetic study of paclitaxel and irinotecan for patients with advanced non-small cell lung cancer

Eur J Cancer. 2002 Sep;38(14):1871-8. doi: 10.1016/s0959-8049(02)00231-9.


We conducted a phase I study of paclitaxel and irinotecan (CPT-11) in advanced non-small cell lung cancer (NSCLC). This study aimed to determine the maximum tolerated doses (MTD). The pharmacokinetics of CPT-11 and its major active metabolite, SN-38, were also analysed. Patients received paclitaxel (day 1) followed by CPT-11 (days 1, 8 and 15), in a 4-week cycle, and paclitaxel and CPT-11 were escalated from 120 and 40 mg/m(2), respectively. 28 patients were enrolled, who were evaluated for toxicity. 2 of 6 patients at 210 mg/m(2) paclitaxel and 50 mg/m(2) CPT-11, and 2 of 4 at 180 and 60 mg/m(2) developed dose-limiting toxicity (DLT) (neutropenia, fever, neurotoxicity and diarrhoea). The area under the plasma concentration-time curve (AUC) of CPT-11 on day 1 was significantly higher than that on days 8 or 15 at each dose level (P=0.002). The AUC of SN-38 on day 1 was significantly increased using paclitaxel doses >or=150 mg/m(2). A preceding paclitaxel administration changed the pharmacokinetics of CPT-11 and SN-38. However, the toxicity was tolerable. Paclitaxel 180 mg/m(2) and CPT-11 50 mg/m(2) were the recommended doses for further phase II study of this combination.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Hematologic Diseases / chemically induced
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics


  • Irinotecan
  • Paclitaxel
  • Camptothecin