title: EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib.
abstract: Gefitinib--a specific inhibitor of epidermal growth factor receptor (EGFR)-associated tyrosine kinase--has demonstrated efficacy in a subgroup of patients with non-small-cell lung carcinoma (NSCLC) who fail conventional chemotherapy. It is also reported to have an antitumor effect in brain metastases from NSCLC. Additionally, EGFR mutations have shown a strong association with gefitinib sensitivity for NSCLC. Here, we assessed the efficacy of gefitinib in brain metastases from NSCLC and evaluated the association of this efficacy with EGFR mutations. We retrospectively reviewed eight cases in which patients were suffering from brain metastases before the initiation of gefitinib treatment. Brain tumor response could be evaluated by MRI in these patients; EGFR gene analyses were also available. We evaluated whether objective tumor response was observed after gefitinib treatment and assessed the efficacy of gefitinib as effective, noneffective, or not assessable in consideration of the influence of previous radiotherapy. Of the eight patients, the efficacy of gefitinib was assessed as effective in three and as noneffective in three. All three patients demonstrating effective efficacy had EGFR mutations in the tyrosine kinase domain (deletion mutation in two patients and point mutation in one patients), whereas none of the three patients demonstrating noneffective efficacy had EGFR mutations. Gefitinib appears to be effective in treating brain metastases in a subgroup of patients. Our data suggested a possible association between the efficacy of gefitinib in the treatment of brain metastases and EGFR mutations.
authors.affiliation: Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kosaka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mizuno
authors.forename: Norimoto
authors.initials: N
authors.lastname: Nakahara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hatano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.forename: Dai
authors.initials: D
authors.lastname: Ishii
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib