The paradoxical effect of bevacizumab in the therapy of malignant gliomas
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Abstract
One rationale behind the use of agents that inhibit vascular endothelial growth factor in the therapy of primary CNS malignancies is based upon the concept that normalization of tumor vasculature with a decrease in tumor interstitial pressure will improve access of cytoreductive drugs and improve radiotherapy efficacy due to increased oxygen delivery. However, several studies have raised the concern that these agents may both rapidly restore the low permeability characteristics of the blood–brain barrier and counteract the beneficial effect of pseudoprogression. The result may be decreased therapeutic efficacy while increasing infiltration by co-opting normal vessels. In this discussion, we examine both histologic and radiographic tumor progression in the context of antiangiogenic agents. Issues dealing with the safety of bevacizumab (Avastin®, Genentech, South San Francisco, CA) and its potential to decrease efficacy of standard radiochemotherapy when used to treat patients with newly diagnosed malignant glioma are emphasized.
Footnotes
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- BBB
- blood–brain barrier
- DCE
- dynamic contrast enhancement
- DSC
- dynamic susceptibility contrast
- FDA
- Food and Drug Administration
- FLAIR
- fluid-attenuated inversion recovery
- GBCA
- gadolinium-based contrast agent
- GBM
- glioblastoma multiforme
- IgG
- immunoglobulin G
- OS
- overall survival
- PFS
- progression-free survival
- RANO
- Response Assessment in Neuro-Oncology Working Group
- rCBV
- relative cerebral blood volume
- RTOG
- Radiation Oncology Therapy Group
- VEGF
- vascular endothelial growth factor
- Received June 3, 2010.
- Accepted August 24, 2010.
- Copyright © 2010 by AAN Enterprises, Inc.
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Letters: Rapid online correspondence
- The paradoxical effect of bevacizumab in the therapy of malignant gliomas
- Marc C. Chamberlain, University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, 825 Eastlake Ave. E, P.O. Box 19023, Seattle, WA 98109-1023chambemc@u.washington.edu
Submitted April 01, 2011 - Reply from the authors
- Edward A. Neuwelt, Oregon Health & Science University, 3181 Sam Jackson Parkway Road, L603, Portland, OR 97239neuwelte@ohsu.edu
- Eric M. Thompson, Eugene P. Frenkel
Submitted April 01, 2011
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