[A phase I study of gemcitabine and irinotecan as second line treatment for advanced non-small cell lung cancer]

A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of gemcitabine and irinotecan combination therapy as second line treatment in patients with advanced non-small cell lung cancer (NSCLC). Twelve patients with measurable NSCLC (age range 46-74 years; 7 males, 5 females; performance status 0 = 4, 1 = 8) who progressed or failed first-line chemotherapy were enrolled. Prior chemotherapy was platinum-based without gemcitabine or irinotecan. Gemcitabine was administered at a fixed dose of 1,000 mg/m2 after irinotecan administration, and irinotecan was administered at doses from 50 to 125 mg/m2 with an increment of 25 mg/m2, both on day 1 and 8. Chemotherapy was repeated every 3 weeks. Grade 3/4 leukopenia occurred in three patients (25%), neutropenia in four (33%), anemia in one (8%), and thrombocytopenia in one (8%). Grade 3 nausea and vomiting was observed in three (25%), grade 2 diarrhea in one (8%), and liver dysfunction in one (8%). Other toxicities were mild. Two of the three patients at level 4 (irinotecan 125 mg/m2) experienced dose limiting toxicity: one patient experienced grade 4 leukopenia and neutropenia, and the other experienced treatment delay of more than 2 weeks. The objective response rate was 16.6% (2/12). The maximum tolerated dose in this combination therapy was gemcitabine 1,000 mg/m2 and irinotecan 125 mg/m2. The dose level of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 on day 1 and 8 of a 3-week cycle is recommended for a phase II study.