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First published on January 20, 2006
A more recent version of this article appeared on April 1, 2006
Neuro Oncol 2006, DOI:10.1215/15228517-2005-002
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© Copyright 2005 by the Society for Neuro-Oncology

Received April 14, 2005
Accepted August 29, 2005

Clinical Investigations

EGFR mutations in patients with brain metastases from lung cancer: Association with the efficacy of gefitinib

Jun Yoshida 1*, Shinji Shimato 1, Tetsuya Mitsudomi 2, Takayuki Kosaka 2, Yasushi Yatabe 3, Toshihiko Wakabayashi 1, Masaaki Mizuno 1, Norimoto Nakaharai 1, Hisashi Hatano 1, Atsushi Natsume 1, Dai Ishii 1

1 Department of Neurosurgery, Nagoya University Graduate School of Medicine
2 Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya
3 Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya

* To whom correspondence should be addressed. E-mail: jyoshida{at}med.nagoya-u.ac.jp.


   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.

Key Words: brain metastases, EGFR, gefitinib, mutation


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Copyright 2006 by Society for Neuro-Oncology