Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer

J Clin Oncol. 1997 Mar;15(3):884-92. doi: 10.1200/JCO.1997.15.3.884.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / blood
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / adverse effects
  • Ifosfamide / blood
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Survival Analysis
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives
  • Vinblastine / blood
  • Vinorelbine


  • Granulocyte Colony-Stimulating Factor
  • Vinblastine
  • Vinorelbine
  • Ifosfamide