Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03)

Eur J Cancer. 2012 Feb;48(3):377-84. doi: 10.1016/j.ejca.2011.10.016. Epub 2011 Nov 15.

Abstract

Purpose: Patients with brain metastases (BM) rarely survive longer than 6months and are commonly excluded from clinical trials. We explored two combined modality regimens with novel agents with single agent activity and radiosensitizing properties.

Patients and methods: In this randomised phase II trial patients with BM from NSCLC were randomly assigned to 30Gy WBRT with either concomitant gefitinib (GFT) 250mg/day continuously or temozolomide (TMZ) 75mg/m(2) for 21/28days. The primary end-point was overall survival, with quality of life and cognitive function as secondary end-points.

Results: We enrolled 59 patients (GFT 16, TMZ 43), and 56 patients have died, mainly (80%) from disease progression. Four patients succumbed complications of the disease or corticosteroids (intestinal perforation (2), CNS haemorrhage and pulmonary emboli). Median overall survival in the gefitinib arm was 6.3months (95% CI 2.1-14.6), and 4.9months (95% CI 2.3-5.6) in TMZ treated patients. Fatigue was the main complaint.

Conclusions: No relevant toxicity with those therapeutic regimens was observed. Fatal outcome in three patients may have been related to corticosteroids. Cognitive function improved during treatment. However, median overall survival for all patients was only 4.9months (95% CI 2.3-5.7) and 1-year survival 25.4% (95% CI 15.4-37.0%).

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / physiopathology
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy*
  • Brief Psychiatric Rating Scale
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy / methods
  • Cognition* / drug effects
  • Cognition* / physiology
  • Cognition* / radiation effects
  • Cranial Irradiation* / adverse effects
  • Cranial Irradiation* / methods
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Quality of Life*
  • Quinazolines / therapeutic use*
  • Survival Analysis
  • Temozolomide

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Dacarbazine
  • Gefitinib
  • Temozolomide