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

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.

• Authors: Hiroshi Nokihara, Noboru Yamamoto, Yasuhide Yamada, Kazuhiko Yamada, Taizo Hirata, Yasushi Goto, Maki Tanioka, Yoko Ikeda, Tomohide Tamura
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 70 Issue 4 Pg. 559-65 (Oct 2012) ISSN: 1432-0843 [Electronic] Germany
• PMID: 22878519 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• BMS-690514
• Piperidines
• Pyrroles
• Triazines
• Fluorodeoxyglucose F18

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, blood, therapeutic use)
• Female
• Fluorodeoxyglucose F18
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasms (drug therapy, pathology)
• Piperidines (administration & dosage, adverse effects, blood, therapeutic use)
• Positron-Emission Tomography
• Pyrroles (administration & dosage, adverse effects, blood, therapeutic use)
• Triazines (administration & dosage, adverse effects, blood, therapeutic use)