Phase I and pharmacokinetic study of dasatinib and cetuximab in patients with advanced solid malignancies.

ABSTRACT:

Background

Combined inhibition of epidermal growth factor receptor (EGFR) and Src family kinases (SFK) may lead to improved therapeutic effects. We evaluated the combination of dasatinib, an inhibitor of SFK and other kinases, and cetuximab, an anti-EGFR monoclonal antibody.

Patients and methods

Patients with advanced solid malignancies received cetuximab intravenously on a standard weekly schedule and dasatinib orally, once daily at 3 dose levels: (1) 100 mg, (2) 150 mg, (3) 200 mg. Pharmacokinetic and pharmacodynamic studies of dasatinib were performed prior to starting cetuximab and following 14 days of treatment.

Results

Twenty-five patients (3 dose level 1; 19 dose level 2; 3 dose level 3) were initially treated. Three patients developed dose-limiting toxicities:

SUBMITTER: Argiris A 

PROVIDER: S-EPMC3402509 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature