title: Bevacizumab treatment for human glioblastoma. Can it induce cognitive impairment?
abstract: Recent results from 2 double-blind, placebo-controlled phase III trials (RTOG 0825) and (AVAglio) for first-line treatment of glioblastoma patients with the VEGF antibody bevacizumab, showed similar results, related to overall and progression-free survival. The RTOG 0825 trial indicated, opposed to the AVAglio trial, that patients treated with bevacizumab showed a decline in global neurocognitive function compared to untreated patients, -a decline that was most obvious after prolonged treatment. At present, there is a considerably controversy related to these observations. In the present work we point at the possibility that bevacizumab treatment of the normal brain can reduce synaptic plasticity in the hippocampus. We believe that such a phenomenon may partly explain the reduced cognitive function observed in patients in the RTOG 0825 trial. Since the same effects were not clearly defined in the AVAglio trial, further studies on putative neurocognitive effects after bevacizumab treatment are warranted.
authors.affiliation: Department of Biomedicine, University of Bergen, Norway (P.F., N.O., H.E.,P.Ø.S., R.B); Centre de Recherche Public de la Santé, Luxembourg (D.S., O.K., S.P.N.).
authors.forename: Pakzad
authors.initials: P
authors.lastname: Fathpour
authors.forename: Nina
authors.initials: N
authors.lastname: Obad
authors.forename: Heidi
authors.initials: H
authors.lastname: Espedal
authors.forename: Daniel
authors.initials: D
authors.lastname: Stieber
authors.forename: Olivier
authors.initials: O
authors.lastname: Keunen
authors.forename: Per Ø
authors.initials: PØ
authors.lastname: Sakariassen
authors.forename: Simone P
authors.initials: SP
authors.lastname: Niclou
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000494:pharmacology; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D003072:Cognition Disorders / Q000139:chemically induced*; D005909:Glioblastoma / Q000188:drug therapy*; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3749-54
references.pmid: 21321221
references.citation: Development. 2010 Jan;137(2):261-71
references.pmid: 20040492
references.citation: Cell Signal. 2008 Apr;20(4):714-25
references.pmid: 18221855
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5081-6
references.pmid: 21385942
references.citation: Exp Neurol. 2004 Jun;187(2):246-53
references.pmid: 15144851
references.citation: Cell Mol Life Sci. 2013 May;70(10):1727-37
references.pmid: 23475068
references.citation: J Physiol. 1973 Jul;232(2):331-56
references.pmid: 4727084
references.citation: J Cereb Blood Flow Metab. 2002 Oct;22(10):1170-5
references.pmid: 12368654
references.citation: J Neurosci. 2003 Dec 3;23(35):11036-44
references.pmid: 14657160
references.citation: Endocrinology. 2011 May;152(5):1745-51
references.pmid: 21343256
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10242-7
references.pmid: 10963684
references.citation: Neuroscience. 1999;90(4):1529-41
references.pmid: 10338318
references.citation: Behav Brain Res. 2010 Mar 17;208(1):80-4
references.pmid: 19900484
references.citation: J Biol Chem. 2009 Nov 13;284(46):31498-511
references.pmid: 19755425
references.citation: Brain Res Dev Brain Res. 2004 Jan 31;148(1):59-68
references.pmid: 14757519
references.citation: J Clin Invest. 2009 Nov;119(11):3373-83
references.pmid: 19809162
references.citation: Brain Res Bull. 2011 Nov 25;86(5-6):441-6
references.pmid: 21801813