A phase I study of single-agent BEZ235 special delivery system sachet in Japanese patients with advanced solid tumors

• 豊田, 昌徳

• Watanabe, Koichiro

• Amagasaki, Taro

• Natsume, Kazuto

• Takeuchi, Hiromi

• Quadt, Cornelia

• Shirao, Kuniaki

• 南, 博信

抄録

Purpose BEZ235 is a dual kinase inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin, which are key components of the PI3K pathway. This was an open-label, multicenter, dose-escalation, phase I study of single-agent BEZ235 in Japanese oncology patients to determine the maximum tolerated dose (MTD) of BEZ235 based on dose-limiting toxicities (DLTs). Methods Dose escalation was guided by a standard 3+3 method and was based on DLTs observed in Cycle 1 and other safety, pharmacokinetic, and pharmacodynamic information. A total of 35 adult Japanese patients with advanced solid tumors received BEZ235 according to once daily (qd; n=27) or twice daily (bid; n=8) dosing schedules. Results Two DLTs, namely, allergic reaction and thrombocytopenia, were observed at 1200 and 1400mg qd, respectively, while liver dysfunction was reported as a DLT at 400mg bid. The most common adverse events suspected to be related to BEZ235 in both dosing schedules were diarrhea, nausea, decreased appetite, stomatitis, and thrombocytopenia. Conclusions Although the MTD was not established, the maximum clinically tolerable dose was determined to be 1200mg because two out of six patients required dose reduction in Cycle 2. The recommended dose was determined to be 1000mg qd, which was comparable with the results of the first-in-human BEZ235 study in Western patients with advanced solid tumors (NCT00620594). Additionally, the tolerability of BEZ235 400mg bid in Japanese oncology patients was confirmed in this study. ClinicalTrials.gov identifier NCT01195376.

収録刊行物

• Cancer Chemotherapy and Pharmacology

  Cancer Chemotherapy and Pharmacology 83 (2), 289-299, 2019-02

  Springer

キーワード

• PI3K
• mTOR
• Phase I
• BEZ235
• Inhibitor

詳細情報

• CRID: 1050856995323308288
• NII論文ID: 120006599080
• ISSN: 14320843
• ISSN: 03445704
• HANDLE: 20.500.14094/90005637
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles