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01-10-2010 | Original Article

Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors

Authors: Yasuhito Fujisaka, Yasuhide Yamada, Noboru Yamamoto, Toshio Shimizu, Yutaka Fujiwara, Kazuhiko Yamada, Tomohide Tamura, Hiroyuki Watanabe, Yu-Nien Sun, Michael B. Bass, Mitsuo Seki

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2010

Abstract

Purpose

The aim of this study was to investigate the safety and pharmacokinetics of motesanib (AMG 706), a small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and c-Kit in Japanese patients with advanced solid tumors.

Methods

Patients were administered motesanib orally once daily (QD) at doses of 50, 100, and 125 mg QD. The total study duration for each patient consisted of three cycles of 28 days per cycle. The primary endpoints were the incidence of dose-limiting toxicities (DLTs), estimation of the maximum tolerated dose (MTD), and assessment of pharmacokinetic parameters of motesanib.

Results

Fifteen patients were enrolled and received motesanib. No DLTs were observed and, therefore, the MTD was not reached. Motesanib had acceptable toxicity at doses up to 125 mg QD. The pharmacokinetics of motesanib appears to be dose proportional. No objective responses per RECIST were observed. However, all 15 patients achieved stable disease, and five patients had durable (>24 weeks) stable disease.

Conclusions

The results of this study demonstrate that motesanib is tolerable in Japanese patients at doses up to 125 mg QD.

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Title: Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors
Authors: Yasuhito Fujisaka
Yasuhide Yamada
Noboru Yamamoto
Toshio Shimizu
Yutaka Fujiwara
Kazuhiko Yamada
Tomohide Tamura
Hiroyuki Watanabe
Yu-Nien Sun
Michael B. Bass
Mitsuo Seki
Publication date: 01-10-2010
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-010-1243-y

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