Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases

Clin Lung Cancer. 2004 Sep;6(2):123-8. doi: 10.3816/CLC.2004.n.026.


The clinical efficacy of gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), on brain metastases (BMs) from non-small-cell lung cancer (NSCLC) was evaluated. Fifteen patients with recurrent NSCLC with metastasis to the brain were treated with gefitinib. The objective tumor response rate (60%; 9 of 15 patients) for BM was the same as for primary tumors. The median time to response of BM was 26 days. In 8 of 9 patients who exhibited partial response in the thoracic lesion, BM showed dramatic regression, including 1 complete response. One patient with stable primary tumor also exhibited partial response in BM with this monotherapy. Brain metastasis-related neurologic symptoms such as hemiparesis, dysarthria, dysphagia, and vertigo improved or disappeared with the objective response of BM as confirmed by magnetic resonance imaging. Central nervous system toxicities were not observed during the treatment. Four of the 9 BM responders are still under treatment with neither adverse events nor disease progression. Two discontinued the treatment because of severe hepatic toxicity and 3 died because of acquired resistance in pulmonary lesions, even though partial response was observed in the BMs. Finally, median duration of response of BM was 8.7 months and median overall survival was 8.3 months (range, 1.8 to > 15.7 months). Molecular targeted therapy against EGFR could be an option for the treatment of BM from NSCLC refractory to conventional chemotherapy plus radiation therapy because it has demonstrated a distinct therapeutic potential against BM compared with primary lung tumor and extracranial metastases.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Protein Kinase Inhibitors / administration & dosage
  • Quinazolines / administration & dosage*
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome


  • Protein Kinase Inhibitors
  • Quinazolines
  • Gefitinib