title: Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene.
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.
authors.affiliation: Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. t-fuku@idac.tohoku.ac.jp
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Saijo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sakakibara
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.forename: Naoto
authors.initials: N
authors.lastname: Morikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kanamori
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy / Q000556:secondary*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy / Q000556:secondary; D008581:Meningitis / Q000188:drug therapy / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000008:administration & dosage*; D011878:Radiotherapy
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib