Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene

Tohoku J Exp Med. 2008 Apr;214(4):359-63. doi: 10.1620/tjem.214.359.

Abstract

Carcinomatous meningitis is a severe complication of lung cancer. Although treatment with gefitinib, a tyrosine kinase inhibitor of epidermal growth factor (EGF) receptor, has been reported to be highly effective against lung cancers harboring a mutated EGF gene, its effect against carcinomatous meningitis is unknown. Here, we report successful treatment of carcinomatous meningitis with gefitinib in a lung cancer patient suffered from meningeal metastasis. A 62-year-old, non-smoking, Japanese male was admitted for headache, failing vision, and temporary loss of consciousness and was subsequently diagnosed with stage IV lung adenocarcinoma and carcinomatous meningitis. A tumor sample revealed the in-frame deletion of codons 746 to 750 (E746 to A750) in exon 19 of the EGF gene, which leads to constitutive activation of the tyrosine kinase domain and high-affinity binding of gefitinib. The patient's performance status was poor owing to progression of the meningitis and elevated cerebrospinal fluid (CSF) pressure. Combined treatment with gefitinib (250 mg/day) and whole-brain irradiation (36 Gray total) proved to be effective. It is noteworthy that the level of gefitinib in the CSF was less than 1% of the serum level (serum: 117 nM before drug re-administration and 132 nM 2 hrs later; CSF: 0.9 nM both before and 2 hrs after drug re-administration). Gefitinib treatment should be considered for patients with carcinomatous meningitis and lung adenocarcinoma harboring a mutated EGF gene.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / secondary*
  • Antineoplastic Agents / administration & dosage*
  • Combined Modality Therapy
  • ErbB Receptors / genetics*
  • Gefitinib
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / radiotherapy
  • Male
  • Meningeal Neoplasms / drug therapy*
  • Meningeal Neoplasms / genetics
  • Meningeal Neoplasms / radiotherapy
  • Meningeal Neoplasms / secondary
  • Meningitis / drug therapy
  • Meningitis / etiology
  • Meningitis / genetics
  • Middle Aged
  • Mutation
  • Quinazolines / administration & dosage*
  • Radiotherapy

Substances

  • Antineoplastic Agents
  • Quinazolines
  • ErbB Receptors
  • Gefitinib