Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer

J Natl Cancer Inst. 2005 Apr 6;97(7):499-506. doi: 10.1093/jnci/dji096.

Abstract

Background: Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC).

Methods: Patients with stage IIIB NSCLC were treated with two monthly MIC cycles followed by radiotherapy; those with "wet" stage IIIB (pleural or pericardial involvement), with stage IIIB with supraclavicular node involvement, or stage IV (i.e., metastatic) NSCLC were treated with four monthly MIC cycles. Patients who responded to induction treatment were randomly assigned to receive intravenous vinorelbine at a dose of 25 mg x m(-2) x wk(-1) for 6 months or no further treatment. Survival comparisons used the log-rank test and the Cox regression adjusted for stage. All statistical tests were two-sided.

Results: A total of 573 patients were registered, of whom 227 responded to induction treatment and 181 were randomly assigned (91 to maintenance vinorelbine and 90 to observation) between January 1994 and March 2000. One- and 2-year survival rates were 42.2% and 20.1% in the vinorelbine arm and 50.6% and 20.2% in the observation arm, respectively (log-rank P = .48). The hazard ratio of survival after adjustment on stage, in the vinorelbine arm relative to the observation arm, was 1.08 (95% confidence interval = 0.79 to 1.47; P = .65). There was also no difference between arms in progression-free survival (log-rank P = .32).

Conclusion: Maintenance vinorelbine did not improve survival of patients with advanced NSCLC who responded to induction MIC treatment. Nevertheless, other agents, including docetaxel and targeted agents, should be evaluated as maintenance agents before the concept is abandoned.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Neoplasm Staging
  • Odds Ratio
  • Proportional Hazards Models
  • Remission Induction
  • Survival Analysis
  • Treatment Failure
  • Treatment Outcome
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use*
  • Vinorelbine

Substances

  • Antineoplastic Agents, Phytogenic
  • Mitomycin
  • Vinblastine
  • Cisplatin
  • Vinorelbine
  • Ifosfamide

Supplementary concepts

  • MIP protocol