Journal of Clinical Oncology, Vol 15, 884-892, Copyright © 1997 by American Society of Clinical Oncology
Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer
GA Masters, PC Hoffman, A Hsieh, LC Drinkard, R Mick, BL Samuels, A Guaspari, HM Golomb and EE Vokes
Department of Medicine, University of Chicago Cancer Research Center, IL 60637-1470, USA.
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 this
combination. PATIENTS AND METHODS: Cohorts of patients with stage IIIB or
IV non-small-cell lung cancer (NSCLC) and no prior chemotherapy received
vinorelbine starting at 15 mg/m2 on days 1, 2, and 3, and ifosfamide
starting at 2.0 g/m2 on days 1, 2, and 3 with G-CSF support for all
patients. Cycles were repeated every 21 days. Plasma vinorelbine
concentrations were also analyzed. RESULTS: Forty-two patients were
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/m2 for 3 days. The
recommended phase II dose was vinorelbine 30 mg/m2 with ifosfamide 1.6 g/m2
both given on 3 consecutive days. The overall response rate was 40% (17 of
42; all partial responders). The median survival duration was 50 weeks,
with a 1-year survival rate of 48%. Pharmacokinetic analysis showed that
vinorelbine in this combination and on this schedule 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 encouraging 1-year survival rate
of 48%, further investigation of this new vinorelbine schedule is warranted
in this and other combination regimens.
