Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of central nerve system metastases from non-small cell lung cancer

Cancer Lett. 2014 Aug 28;351(1):6-12. doi: 10.1016/j.canlet.2014.04.019. Epub 2014 May 23.


Brain metastases (BM) are common and disastrous occurrence in patients with non-small cell lung cancer (NSCLC). Currently increasing studies suggest remarkable efficacy and mild toxicity of the epidermal growth factor tyrosine kinase inhibitor (EGFR TKI) in these patients, making targeted therapy an attractive option to BM from NSCLC. We here present a review about the use of EGFR-TKIs in this context and the following questions would be discussed: Are TKIs capable of permeating across brain-blood barrier (BBB)? How to boost exposure of EGFR TKI in cerebrospinal fluid to overcome the resistance of refractory metastases? Would the combination with other treatment like radiotherapy bring about advanced effect? And which patients with BM is the fittest population to EGFR-TKI treatment? In fact, though the administration of EGFR TKI only could achieve certain effect with limited penetration across BBB, increasing dose and combined radiotherapy would carry out better outcome. Unsurprisingly EGFR mutations were still the most important predictor of the sensitivity.

Keywords: Brain metastasis; EGFR TKI; NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Blood-Brain Barrier
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Chemoradiotherapy
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib