Phase I study of combined therapy with vorinostat and gefitinib to treat BIM deletion polymorphism-associated resistance in EGFR-mutant lung cancer (VICTROY-J): A study protocol

Shinji Takeuchi, Kenichi Yoshimura, Tadami Fujiwara, Masahiko Ando, Shinobu Shimizu, Katsuhiko Nagase, Yoshinori Hasegawa, Toshiaki Takahashi, Nobuyuki Katakami, Akira Inoue, Seiji Yano

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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 thata 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 (200-400 mg) 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 Istudy of combined therapy with vorinostat and gefitinib for NSCLC patients double selected for an EGFR mutation and BIM deletion polymorphism.

Original languageEnglish
Pages (from-to)321-325
Number of pages5
JournalJournal of Medical Investigation
Volume64
Issue number3-4
DOIs
Publication statusPublished - 2017

Keywords

  • BIMpolymorphism
  • EGFR mutation
  • Gefitinib
  • Non-small cell lung cancer
  • Vorinostat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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