title: Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.
abstract: OBJECTIVE
  Motesanib (AMG 706) is a multitargeted anticancer agent with an inhibitory action on the human vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and the cellular stem-cell factor receptor (KIT). The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.
  
  
  METHODS
  All patients had experienced progression or relapse while undergoing with imatinib as 400 mg/day or higher. The patients were administered 125 mg of motesanib once daily. The primary endpoint was overall response. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumor, and safety was assessed according to the Common Terminology Criteria for Adverse Events (version 3).
  
  
  RESULTS
  Of 35 enrolled and treated patients, no patient showed a complete response, and one patient showed a partial response (PR). Seven had stable disease (SD) for at least 24 months, two of whom continued to have SD for more than 2 years. The median progression-free survival time was 16.1 weeks. Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue. Anemia was the only hematological toxicity that was reported.
  
  
  CONCLUSIONS
  One patient showed PR, and seven patients showed SD more than 24 weeks. Motesanib was found to be safe and well tolerated. The observed toxicities were consistent with Phase I study findings.
authors.affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan. asawaki@aichi-cc.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaki
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.forename: Masato
authors.initials: M
authors.lastname: Koseki
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Yu-Nien
authors.initials: YN
authors.lastname: Sun
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D004361:Drug Tolerance; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009841:Oligonucleotides; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D009841:Oligonucleotides; D010879:Piperazines; D011743:Pyrimidines; D009536:Niacinamide; D000068877:Imatinib Mesylate; C519562:imetelstat
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