title: A phase I study of BMS-690514 in Japanese patients with advanced or metastatic solid tumors.
abstract: OBJECTIVE
  BMS-690514 is a novel oral tyrosine kinase inhibitor of ErbB and vascular endothelial growth factor receptor. This open-label phase I dose-escalation study (ClinicalTrials.gov Identifier: NCT00516451) aimed to assess the safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics of BMS-690514 in Japanese patients with advanced or metastatic solid tumors.
  
  
  METHODS
  Patients with advanced or metastatic solid tumors received oral BMS-690514 once daily continuously until disease progression or intolerable toxicity occurred. Dose-limiting toxicity (DLT) was evaluated from the first dose to Day 29. Dose levels at 100 and 200 mg were investigated. Assessments included adverse events, tumor response, pharmacokinetics, pharmacodynamics, 2 [18F] fluoro-2-deoxyglucose positron-emitting tomography, and epidermal growth factor receptor and K-ras mutations.
  
  
  RESULTS
  BMS-690514 at the dose of 100 mg (n = 3) or 200 mg (n = 3) was administered once daily to totally nine patients and was well tolerated up to 200 mg. No treatment-related serious adverse events or DLTs were reported. Frequently observed treatment-related AEs were acne, diarrhea, dry skin, hypertension, stomatitis, blood fibrinogen increased, hemoglobin decreased, pruritus, and hypoalbuminemia. These were generally reported as Grade 1 and 2. Five of 9 patients (56 %) had stable disease. Plasma concentrations of BMS-690514 reached Cmax within 3 h and declined with an effective half-life of approximately 10 and 12 h at 100 and 200 mg, respectively.
  
  
  CONCLUSIONS
  Oral BMS-690514 was well tolerated in Japanese patients with advanced or metastatic solid tumors up to 200 mg.
authors.affiliation: Internal Medicine and Thoracic Oncology, Division of Internal Medicine, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Taizo
authors.initials: T
authors.lastname: Hirata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Goto
authors.forename: Maki
authors.initials: M
authors.lastname: Tanioka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C552150:BMS-690514; D010880:Piperidines; D011758:Pyrroles; D014227:Triazines; D019788:Fluorodeoxyglucose F18