A phase I trial of enzastaurin in patients with recurrent gliomas.

ABSTRACT:

Purpose

Enzastaurin is a selective inhibitor of protein kinase C beta. Prior phase I studies did not show increased drug exposures with escalating once daily administration. Limits from gastrointestinal absorption may be overcome by twice daily dosing, potentially improving antitumor effects.

Experimental design

We conducted a phase I dose escalation study in 26 patients with recurrent malignant glioma, stratified by use of enzyme-inducing antiepileptic drugs, to investigate whether divided twice daily dosing results in higher exposures compared with once daily dosing. Phosphorylated glycogen synthase 3 beta was analyzed as a potential biomarker of enzastaurin activity.

Results

Enzastaurin was poorly tolerated at all dose levels evaluated (500, 800, and 1,000 mg total

SUBMITTER: Kreisl TN 

PROVIDER: S-EPMC7227612 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature