title: Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan. yfujisaka@gmail.com
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Fujisaka
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yu-Nien
authors.initials: YN
authors.lastname: Sun
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bass
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Seki
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009841:Oligonucleotides; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; C519562:imetelstat