Dose intensification--a phase I study of ifosfamide with vinorelbine (Navelbine): rationale and study design in...

A phase I trial of a combination of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) and ifosfamide given on a novel schedule on 3 consecutive days with granulocyte colony-stimulating factor was conducted to establish the maximum tolerated dose of vinorelbine and the dose-limiting toxicities of this regimen. Doses of vinorelbine were escalated in cohorts of patients. Of the 29 patients enrolled at the time of data analysis, 26 were evaluable for toxicity. At the first dose level (ifosfamide 2.0 g/m2 days 1, 2, and 3; vinorelbine 15 mg/m2 days 1, 2, and 3), two of three patients had dose-limiting toxicities. The dose of ifosfamide was decreased by 20%, and dose escalation of vinorelbine was restarted. At the vinorelbine dose level of 35 mg/m2/d for 3 days, three of four patients had dose-limiting toxicities. The recommended phase II doses were established as 1.6 g/m2/d ifosfamide for 3 days and 30 mg/m2/d vinorelbine for 3 days. This study established that granulocyte colony-stimulating factor was needed for approximately 8 days. We are currently examining the feasibility of two dose levels of vinorelbine (25 mg/m2 and 30 mg/m2/d for 3 days) in combination with ifosfamide (1.6 g/m2/d) given every 2 weeks.