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PMID: 17222792 Published · ppublish English Clinical Trial, Phase II Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients.

Cancer cell ·Vol. 11 ·No. 1 ·2007-01-00 ·Pages 83-95

Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK

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.

MeSH Terms
Brain Edema/drug therapy,etiology Brain Neoplasms/blood supply,complications,drug therapy Chemokine CXCL12 Chemokines, CXC/blood Endothelial Cells/drug effects Enzyme-Linked Immunosorbent Assay Fibroblast Growth Factors/blood,drug effects Flow Cytometry Glioblastoma/blood supply,complications,drug therapy Humans Image Processing, Computer-Assisted Magnetic Resonance Imaging Neoplasm Recurrence, Local/complications,drug therapy Neoplastic Cells, Circulating/drug effects Neoplastic Stem Cells/drug effects Neovascularization, Pathologic/drug therapy Protein Kinase Inhibitors/therapeutic use Quinazolines/therapeutic use Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors Survival Analysis
Chemicals
CXCL12 protein, human Chemokine CXCL12 Chemokines, CXC Protein Kinase Inhibitors Quinazolines Fibroblast Growth Factors Receptors, Vascular Endothelial Growth Factor cediranib
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Batchelor Tracy T
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. tbatchelor@partners.org
Sorensen A Gregory
di Tomaso Emmanuelle
Zhang Wei-Ting
Duda Dan G
Cohen Kenneth S
Kozak Kevin R
Cahill Daniel P
Chen Poe-Jou
Zhu Mingwang
Ancukiewicz Marek
Mrugala Maciej M
Plotkin Scott
Drappatz Jan
Louis David N
Ivy Percy
Scadden David T
Benner Thomas
Loeffler Jay S
Wen Patrick Y
Jain Rakesh K
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1535-6108
DOI
10.1016/j.ccr.2006.11.021
Email
tbatchelor@partners.org
Published
2007-01-00
Pages
83-95
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC2748664
Subset
IM
Grants
NCRR NIH HHS · P41-RR14075 · United States
NCI NIH HHS · R21 CA117079-02 · United States
NCI NIH HHS · R01 CA057683-15 · United States
NCRR NIH HHS · M01 RR001066-26 · United States
NCI NIH HHS · R21 CA117079 · United States
NCI NIH HHS · R01 CA115767-03 · United States
NCI NIH HHS · P01CA80124 · United States
NCRR NIH HHS · P41 RR014075 · United States
NCRR NIH HHS · M01 RR001066 · United States
NCI NIH HHS · R21CA117079 · United States
NCI NIH HHS · R01 CA057683 · United States
NCI NIH HHS · P01 CA080124 · United States
NCRR NIH HHS · P41 RR014075-10 · United States
NCI NIH HHS · R01CA115767 · United States
NCI NIH HHS · R01CA57683 · United States
NCRR NIH HHS · M01-RR-01066 · United States
NCI NIH HHS · R01 CA115767 · United States
NCI NIH HHS · P01 CA080124-08 · United States
Corrections
CommentIn
PMID: 17222788
CommentIn
PMID: 17609654
External Links
PubMed source DOI: 10.1016/j.ccr.2006.11.021 PMC Full Text View journal details
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