TY - JOUR
T1 - Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene
AU - Fukuhara, Tatsuro
AU - Saijo, Yasuo
AU - Sakakibara, Tomohiro
AU - Inoue, Akira
AU - Morikawa, Naoto
AU - Kanamori, Masayuki
AU - Nakashima, Ichiro
AU - Nukiwa, Toshihiro
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/4/26
Y1 - 2008/4/26
N2 - 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.
AB - 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.
KW - Carcinomatous meningitis
KW - EGF
KW - EGF-TKI
KW - Gefitinib
KW - Lung cancer
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U2 - 10.1620/tjem.214.359
DO - 10.1620/tjem.214.359
M3 - Article
C2 - 18441512
AN - SCOPUS:44449131799
VL - 214
SP - 359
EP - 363
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
SN - 0040-8727
IS - 4
ER -