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

Tatsuro Fukuhara, Yasuo Saijo, Tomohiro Sakakibara, Akira Inoue, Naoto Morikawa, Masayuki Kanamori, Ichiro Nakashima, Toshihiro Nukiwa

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)359-363
Number of pages5
JournalTohoku Journal of Experimental Medicine
Volume214
Issue number4
DOIs
Publication statusPublished - 2008 Apr 26

Keywords

  • Carcinomatous meningitis
  • EGF
  • EGF-TKI
  • Gefitinib
  • Lung cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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