GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine-cisplatin with vinorelbine-ifosfamide-cisplatin in metastatic non-small-cell lung cancer patients

Ann Oncol. 2002 Dec;13(12):1853-61. doi: 10.1093/annonc/mdf316.

Abstract

Background: The standard doublet, vinorelbine-cisplatin, was compared with a triplet of vinorelbine-ifosfamide-cisplatin, in terms of survival, in patients with advanced non-small-cell lung cancer (NSCLC).

Patients and methods: From February 1998 to June 1999, 259 chemonaïve patients entered the study and were randomised to receive either vinorelbine-cisplatin (NP; vinorelbine 30 mg/m(2) on days 1, 8 and 15 with cisplatin 80 mg/m(2) on day 1) or vinorelbine-ifosfamide-cisplatin (NIP; vinorelbine 25 mg/m(2) on days 1 and 8, ifosfamide 3 g/m(2) on day 1 and cisplatin 75 mg/m(2) on day 1), with both regimens being repeated every 3 weeks. All patients had stage IV or relapsed disease and a performance score of 0 or 1.

Results: The overall response rate was 34.6% for NP and 35.7% for NIP. Median and 1-year survival rates were 10.0 months and 38.4% for NP, and 8.2 months and 33.7% for NIP, respectively. A median of four cycles was administered in each arm. The major World Health Organization grade 3-4 toxicities for NP and NIP, respectively, were: neutropenia (20.3% compared with 9% of cycles), anaemia (4.1% compared with 5% of cycles), nausea and vomiting (22.2% compared with 19.4% of patients) and alopecia (5.6% compared with 29.8% of patients). Four toxic deaths occurred in the NP arm and eight in the NIP arm.

Conclusions: The different schedules of vinorelbine in the two arms led to a greater survival in the NP arm without impairing the tolerance profile, although this is not statistically significant. This confirms that the two-drug combination NP is a reference treatment for metastatic NSCLC. The role of three-drug combinations remains questionable in this subset of patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Cisplatin / administration & dosage
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Prospective Studies
  • Quality of Life*
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives*
  • Vinorelbine

Substances

  • Vinblastine
  • Cisplatin
  • Vinorelbine
  • Ifosfamide