Phase I and Pharmacokinetic Study of Combination Chemotherapy Using Irinotecan and Paclitaxel in Patients with Lung Cancer

The purpose of this study was to investigate the maximum tolerated doses, dose-limiting toxicities, efficacy, and pharmacokinetic profiles in the combination of irinotecan and paclitaxel. Eligibility criteria included age 75 years or younger, good performance status, adequate organ function, and unresectable non–small cell or extensive disease of small cell lung cancer. Irinotecan was administered on days 1 and 8 over 90 minutes, and paclitaxel was administered on day 8 over 3 hours after 90 minutes from the end of the irinotecan infusion. Irinotecan and paclitaxel were dose-escalated from 40 and 135 mg/m2 and repeated every 4 weeks. The authors also administered a higher dosage with preventive granulocyte colony-stimulating factor support from day 9. Thirty-one patients were assessed for toxicities and responses. Dose-limiting toxicities were neutropenia and febrile neutropenia. The dose of irinotecan 60 mg/m2 and paclitaxel 200 mg/m2 with preventive granulocyte colony-stimulating factor support was tolerable and suitable for a phase II trial. Nine of 25 (36%) patients with non–small cell and all six patients with small cell carcinoma achieved partial response. The areas under the concentration versus time curves of irinotecan and its metabolites on day 8 were significantly higher than on day 1. This combination therapy must be planned only after careful consideration of the drug–drug interaction.