Tohoku J. Exp. Med., 2008, 214(4)

Successful Treatment of Carcinomatous Meningitis with Gefitinib in a Patient with Lung Adenocarcinoma Harboring a Mutated EGF Receptor Gene

TATSURO FUKUHARA,¹ YASUO SAIJO,² TOMOHIRO SAKAKIBARA,¹ AKIRA INOUE,¹ NAOTO MORIKAWA,¹ MASAYUKI KANAMORI,³ ICHIRO NAKASHIMA⁴ and TOSHIHIRO NUKIWA¹

¹Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
²Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
³Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan
⁴Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan

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.

keywords —— carcinomatous meningitis; EGF; EGF-TKI; gefitinib; lung cancer

© 2008 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2008, 214, 359-363

Correspondence: Tatsuro Fukuhara, M.D., Ph.D., Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, 4-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

e-mail: t-fuku@idac.tohoku.ac.jp