[en] 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.
Disciplines :
Oncology
Author, co-author :
Fathpour, Pakzad; 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.).
Obad, Nina
Espedal, Heidi
Stieber, Daniel
Keunen, Olivier
Sakariassen, Per Ø
NICLOU, Simone P. ; Department of Biomedicine, University of Bergen, Norway, Centre de Recherche Public de la Santé, Luxembourg
Bjerkvig, Rolf
External co-authors :
yes
Language :
English
Title :
Bevacizumab treatment for human glioblastoma. Can it induce cognitive impairment?
Gilbert MR Dignam J Won M et al. RTOG 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). In: 2013 ASCO Annual Meeting. Chicago Illinois USA 2013. J Clin Oncol 31 2013 (suppl; abstr 1
Henriksson R Bottomley A Mason W et al. Progression-free survival (PFS) and health-related quality of life (HRQoL) in AVAglio a phase III study of bevacizumab (Bv) temozolomide (T) and radiotherapy (RT) in newly diagnosed glioblastoma (GBM). In: 2013 ASCO Annual Meeting. Chicago Illinois USA 2013. J Clin Oncol 31 2013 (suppl; abstr 2005
Khaibullina AA Rosenstein JM Krum JM. Vascular endothelial growth factor promotes neurite maturation in primary CNS neuronal cultures. Brain Res Dev Brain Res. 2004;148(1):59-68
Rosenstein JM Krum JM. New roles for VEGF in nervous tissuebeyond blood vessels. Exp Neurol. 2004;187(2):246-253
Rosenstein JM Mani N Khaibullina A et al. Neurotrophic effects of vascular endothelial growth factor on organotypic cortical explants and primary cortical neurons. J Neurosci. 2003;23(35): 11036-11044
Silverman WF Krum JM Mani N et al. Vascular glial and neuronal effects of vascular endothelial growth factor in mesencephalic explant cultures. Neuroscience. 1999;90(4):1529-1541
Jin KL Mao XO Greenberg DA. Vascular endothelial growth factor: Direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci USA. 2000;97(18):10242-7
Svensson B Peters M Konig HG et al. Vascular endothelial growth factor protects cultured rat hippocampal neurons against hypoxic injury via an antiexcitotoxic caspaseindependent mechanism. J Cereb Blood Flow Metab. 2002;22(10): 1170-1175
Ma Y Liu W Wang Y et al. VEGF protects rat cortical neurons from mechanical trauma injury induced apoptosis via the MEK/ERK pathway. Brain Res Bull. 2011;86(5-6):441-446
Licht T Keshet E. Delineating multiple functions of VEGF-A in the adult brain. Cell Mol Life Sci. 2013;70(10):1727-1737
Licht T Goshen I Avital A et al. Reversible modulations of neuronal plasticity by VEGF. Proc Natl Acad Sci U S A. 2011;108(12): 5081-5086
Adamcio B Sperling S Hagemeyer N et al. Hypoxia inducible factor stabilization leads to lasting improvement of hippocampal memory in healthy mice. Behav Brain Res. 2010;208(1):80-84
Bliss TV Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973;232(2):331-356
Kim BW Choi M Kim YS et al. Vascular endothelial growth factor (VEGF) signaling regulates hippocampal neurons by elevation of intracellular calcium and activation of calcium/calmodulin protein kinase II and mammalian target of rapamycin. Cell Signal. 2008; 20(4):714-725
Licht T Eavri R Goshen I et al. VEGF is required for dendritogenesis of newly born olfactory bulb interneurons. Development. 2010;137(2): 261-271
Weidemann A Kerdiles YM Knaup KX et al. The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. J Clin Invest. 2009;119(11):3373-3383
Barouk S Hintz T Li P et al. 17beta-estradiol increases astrocytic vascular endothelial growth factor (VEGF) in adult female rat hippocampus. Endocrinology. 2011;152(5): 1745-1751
Keunen O Johansson M Oudin A et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci U S A. 2011;108(9):3749-3754
Panja D Dagyte G Bidinosti M et al. Novel translational control in Arc-dependent long term potentiation consolidation in vivo. J Biol Chem. 2009;284(46):31498-31511.
