ID 111144
著者
Takeuchi, Shinji Kanazawa University
Yoshimura, Kenichi Kanazawa University
Fujiwara, Tadami Nagoya University
Ando, Masahiko Nagoya University
Shimizu, Shinobu Nagoya University
Nagase, Katsuhiko Kanazawa University
Hasegawa, Yoshinori Nagoya University
Takahashi, Toshiaki Shizuoka Cancer Center
Katakami, Nobuyuki Institute of Biomedical Research and Innovation
Inoue, Akira Tohoku University
Yano, Seiji Kanazawa University
キーワード
EGFR mutation
BIM polymorphism
gefitinib
vorinostat
non-small cell lung cancer
資料タイプ
学術雑誌論文
抄録
The BIM deletion polymorphism is reported to be associated with poor outcomes of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR-TKIs, including gefitinib. We have shown that a histone deacetylase inhibitor, vorinostat, can epigenetically restore BIM function and apoptosis sensitivity to EGFR-TKIs in EGFR-mutant NSCLC cells with BIM deletion polymorphisms. The purpose of this study is to determine the feasibility of combined treatment of vorinostat with gefitinib in BIM deletion polymorphism positive EGFR-mutant NSCLC patients. BIM deletion polymorphism positive EGFR mutant NSCLC patients treated with at least one EGFR-TKI and one regimen of chemotherapy are being recruited to this study. Vorinostat (200-400mg) will be administered orally once daily on days 1-7, and gefitinib 250 mg orally once daily on days 1-14. With a fixed dose of gefitinib, the dose of vorinostat will be escalated following a conventional 3+3 design. The primary endpoint is to define the maximum tolerated dose (MTD) of vorinostat combined with 250 mg of gefitinib. This is the first phase I study of combined therapy with vorinostat and gefitinib for NSCLC patients double selected for an EGFR mutation and BIM deletion polymorphism.
掲載誌名
The Journal of Medical Investigation
ISSN
13496867
13431420
cat書誌ID
AA11166929
AA12022913
出版者
Faculty of Medicine Tokushima University
64
3-4
開始ページ
321
終了ページ
325
並び順
321
発行日
2017-08
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版