Phase I study of vinorelbine and irinotecan in previously untreated patients with advanced non-small cell lung cancer

Introduction Vinorelbine alone and irinotecan alone have been shown to have efficacy against non-small cell lung cancer (NSCLC); each drug has different mechanisms of action. A phase I study using a combination of vinorelbine and irinotecan as first-line treatment for advanced NSCLC was done to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Methods Previously untreated patients (≤75 years old) with Stage IIIB or IV NSCLC were enrolled. Based on a 4-week cycle, vinorelbine was given on days 1 and 8, and irinotecan was given on days 1, 8, and 15 intravenously. To prevent an injection site reaction to vinorelbine, the site was treated with topical clobetasol ointment, and the patients were given intravenous dexamethasone prior to vinorelbine treatment. DLT was defined as grade 4 neutropenia lasting ≥4 days or febrile neutropenia, grade 4 thrombocytopenia, ≥grade 3 non-hematological toxicities, or the need to cancel drug administration on both days 8 and 15. Results A total of 23 patients were enrolled. DLT was observed in 1 of 6 patients at level 3 (20 mg/m² vinorelbine, 50 mg/m² irinotecan), in 2 of 3 at level 4 (25 mg/m², 50 mg/m²), and in 2 of 5 at modified level 4 (20, 60 mg/m²). Level 4 and modified level 4 were considered to be the MTD; dose level 3 was therefore recommended. DLTs included liver dysfunction, pneumonitis, colitis, and arrhythmia. Injection site reactions were mild. Hematological and non-hematological toxicities were mild and easily controlled. Conclusion Use of 20 mg/m² vinorelbine on days 1 and 8 followed by 50 mg/m² irinotecan on days 1, 8, and 15 every 4 weeks warrants a phase II study.