AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2007 Jan 16

PMID 17222792

Citations 785

Authors

Tracy T Batchelor

A Gregory Sorensen

Emmanuelle di Tomaso

Wei-Ting Zhang

Dan G Duda

Kenneth S Cohen

Kevin R Kozak

Daniel P Cahill

Poe-Jou Chen

Mingwang Zhu

Marek Ancukiewicz

Maciej M Mrugala

Scott Plotkin

Jan Drappatz

David N Louis

Percy Ivy

David T Scadden

Thomas Benner

Jay S Loeffler

Patrick Y Wen

Rakesh K Jain

Affiliations

Soon will be listed here.

Abstract

Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1alpha, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.

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