Ifosfamide, vinorelbine and gemcitabine in advanced non-small cell lung cancer. A phase I study

The objective of this phase I study was to identify the maximum tolerated d ose (MTD) and toxicity of a three drug, platinum-free regimen, including ge mcitabine, ifosfamide and vinorelbine, in the treatment of patients with ad vanced non-small cell lung cancer (NSCLC). 33 chemotherapy-naive patients w ith histologically confirmed, unresectable NSCLC, received fixed doses of i fosfamide (1500 mg/m(2) days 1-3 with mesna) and vinorelbine (25 mg/m(2) da ys 3 and 8). The gemcitabine dose was escalated from 500 to 1200 mg/m(2) on days 3 and 8 every third week. The escalation was stopped at dose level 4 (gemcitabine 1200 mg/m(2)) since all 3 patients of this cohort showed dose- limiting thrombocytopenia and/or neutropenia at treatment cycle 1. The dose recommended for phase II trials is: gemcitabine 1000 mg/m(2) and vinorelbi ne 25 mg/m(2) given on days 3 and 8 plus ifosfamide 1500 mg/m(2) on days 1- 3. An encouraging response rate of 50% (95% confidence interval (CI): 32-68 %) was observed in 32 patients evaluated. Our results show that ifosfamide, vinorelbine and gemcitabine can be safely administered as outpatient chemo therapy for NSCLC. Myelosuppression is the dose-limiting toxicity (DLT) of this regimen with no major subjective side-effects observed. (C) 1999 Elsev ier Science Ltd. AU rights reserved.