PHASE-I STUDY OF VINORELBINE AND IFOSFAMIDE IN ADVANCED NON-SMALL-CELL LUNG-CANCER

Purpose: We designed a phase I dose-escalation study of vinorelbine on a novel (daily-times-three) schedule with ifosfamide with granulocyte colony-stimulating factor (G-CSF) support to define the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of vinorelbine in thi s combination. Patients and Methods: Cohorts of patients with stage II IB or IV non-small-cell lung cancer (NSCLC) and no prior chemotherapy received vinorelbine starting at 15 mg/m(2) on days 1, 2, and 3, and i fosfamide starting at 2.0 g/m(2) on days 1, 2, and 3 with G-CSF suppor t for all patients. Cycles were repeated every 21 days. Plasma vinorel bine concentrations were also analysed. Results: Forty-two patients we re treated. The median age was 58 years (range, 34 to 75) and 41 had a performance status of 0 or 1. The DLT was neutropenia and sepsis at a maximum-administered vinorelbine dose of 35 mg/m(2) for 3 days, The r ecommended phase II dose was vinorelbine 30 mg/m(2) with ifosfamide 1. 6 g/m(2) both given on 3 consecutive days. The overall response rate w as 40% (17 of 42; all partial responders). The median survival duratio n was 50 weeks, with a I-year survival rate of 48%. Pharmacokinetic an alysis showed that vinorelbine in this combination and on this schedul e is cleared 1.5 to two times faster than in single-agent once-weekly studies. Conclusion: Myelosuppression is the DLT of this regimen with no major subjective toxicities. With tolerable toxicity and an encoura ging 1-year survival rate of 48%, further investigation of this new vi norelbine schedule is warranted in this and other combination regimens . (C) 1997 by American Society of Clinical Oncology.