ID 111144
Author
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
Keywords
EGFR mutation
BIM polymorphism
gefitinib
vorinostat
non-small cell lung cancer
Content Type
Journal Article
Description
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.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
64
Issue
3-4
Start Page
321
End Page
325
Sort Key
321
Published Date
2017-08
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher