A phase I study of BMS-690514 in Japanese patients with advanced or metastatic solid tumorsReport as inadecuate




A phase I study of BMS-690514 in Japanese patients with advanced or metastatic solid tumors - Download this document for free, or read online. Document in PDF available to download.

Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 4, pp 559–565

First Online: 10 August 2012Received: 18 July 2012Accepted: 18 July 2012

Abstract

PurposeBMS-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.

MethodsPatients 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.

ResultsBMS-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.

ConclusionsOral BMS-690514 was well tolerated in Japanese patients with advanced or metastatic solid tumors up to 200 mg.

KeywordsBMS-690514 Tyrosine kinase inhibitor Phase I trial Solid tumor  Download fulltext PDF



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