Phase I dose-escalation study of the pan-HER inhibitor, PF299804, in patients with advanced malignant solid tumors.

ABSTRACT:

Purpose

PF299804 is a potent, orally available, irreversible inhibitor of tyrosine kinase human epidermal growth factor receptors (HER) 1 (EGFR), HER2, and HER4. This first-in-human study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF299804 in patients with advanced solid malignancies.

Experimental design

PF299804 was administered once daily continuously (schedule A) and intermittently (schedule B). Dose escalation proceeded until intolerable toxicities occurred. Skin biopsies were taken predose and after 14 days of treatment to establish a pharmacokinetic/pharmacodynamic relationship. Tumor response was measured once every 2 cycles. Efficacy was correlated with tumor genotypes in non-small cell lung cancer (NSCLC) patients.

Results

SUBMITTER: Janne PA 

PROVIDER: S-EPMC3048920 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature