Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial

Ann Oncol. 2004 Jul;15(7):1042-7. doi: 10.1093/annonc/mdh276.


Background: Brain metastases are a common occurrence in patients with non-small-cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT) is the standard therapy; more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients only. The role of systemic treatments remains controversial. Gefitinib is an oral, highly tolerable, specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, which has shown activity in chemotherapy pre-treated NSCLC. The aim of this study was to evaluate the activity and safety of gefitinib in NSCLC patients with brain metastases.

Patients and methods: From January 2001 to May 2003, 41 consecutive NSCLC patients with measurable brain metastases were treated with gefitinib, given orally at daily dose of 250 mg. Thirty-seven patients had received previous chemotherapy and 18 patients had been treated previously with WBRT, completed at least 3 months before entering the trial.

Results: A partial response (PR) was observed in four patients (10%), with stable disease (SD) in seven cases, for an overall disease control (DC) rate (DC=PR+SD) of 27% (95% confidence interval 13% to 40%). Median duration of PR was 13.5 months. Median progression-free survival (PFS) of the whole population was 3 months. DC rate was higher in patients pre-treated with WBRT (P=0.05) and with adenocarcinoma histological type (P=0.08); adenocarcinoma patients had also a longer PFS (P=0.04). Toxicity was mild and consisted of grade 1/2 skin toxicity and diarrhoea, occurring in 24% and 10% of patients, respectively.

Conclusions: Gefitinib can be active on brain disease in NSCLC patients. Since the results of standard therapy for brain metastases in this clinical setting are particularly disappointing, gefitinib appears to be a possible new treatment option.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Diarrhea / chemically induced
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Radiography
  • Skin Diseases / chemically induced
  • Survival Analysis
  • Treatment Outcome


  • Antineoplastic Agents
  • Quinazolines
  • Gefitinib