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Cancer Chemother Pharmacol. 2012 Oct;70(4):559-65. Epub 2012 Aug 10.

A phase I study of BMS-690514 in Japanese patients with advanced or metastatic solid tumors.

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1
Internal Medicine and Thoracic Oncology, Division of Internal Medicine, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.

Abstract

PURPOSE:

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.

PMID:
22878519
PMCID:
PMC3456941
DOI:
10.1007/s00280-012-1932-9
[Indexed for MEDLINE]
Free PMC Article
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