Activity and toxicity of gemcitabine and gemcitabine + vinorelbine in advanced non-small-cell lung cancer elderly patients: Phase II data from the Multicenter Italian Lung Cancer in the Elderly Study (MILES) randomized trial

Lung Cancer. 2001 Feb-Mar;31(2-3):277-84. doi: 10.1016/s0169-5002(00)00194-x.

Abstract

Background: Following the demonstration that vinorelbine improves survival and quality of life compared with best supportive care in elderly patients with advanced non-small-cell lung cancer (NSCLC), we started the three-arm prospective Multicenter Italian Lung Cancer in the Elderly Study (MILES) trial of vinorelbine, gemcitabine and gemcitabine + vinorelbine.

Design: Within the randomized phase 3 trial, pilot single-stage phase 2 studies were planned for gemcitabine and for gemcitabine + vinorelbine. Eligible patients are aged 70 or more, with stage IV or IIIb (with metastatic supraclavear nodes or malignant pleural effusion) NSCLC. Single-agent gemcitabine is given at 1200 mg/m(2) on days 1 and 8; in the combination, gemcitabine is given at 1000 mg/m(2) and vinorelbine at 25 mg/m(2), both on days 1 and 8, every 3 weeks.

Results: As planned 49 patients were enrolled in each group. Median age was 74 in both groups. Two-thirds of patients had stage IV disease. The response rate was 18.4% (95% exact CI 8.8-32.0) with both treatments. With single-agent gemcitabine main toxicities were grade 4 thrombocytopenia and grade 2 hepatic toxicity, in one patient each, and grade 2 pulmonary toxicity in two patients. With gemcitabine + vinorelbine combination there were grade 4 neutropenia and thrombocytopenia (one patient each), grade 3 anemia requiring red blood cell transfusion (two patients), and grade 4 fever in two patients. Four patients, with severe cardiac comorbidities, suffered grade 3 heart toxicity with atrial flutter or fibrillation, followed by congestive heart failure responsive to treatment.

Conclusion: Both single-agent gemcitabine and the gemcitabine + vinorelbine combination are sufficiently active and tolerable to allow continuation of the MILES study.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Atrial Fibrillation / chemically induced
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chemical and Drug Induced Liver Injury
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology*
  • Female
  • Fever / chemically induced
  • Gemcitabine
  • Humans
  • Infusions, Intravenous
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Neutropenia / chemically induced
  • Thrombocytopenia / chemically induced
  • Vinblastine / adverse effects
  • Vinblastine / analogs & derivatives*
  • Vinblastine / pharmacology*
  • Vinorelbine

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Deoxycytidine
  • Vinblastine
  • Vinorelbine
  • Gemcitabine