Bevacizumab for Glioblastoma Treatment: Reviewing Biological and Clinical Hypothesis for its Success and Failures
Pp. 175-226 (52)
Ana C. Fernandes, Cláudia Caeiro, Vera Miranda-Gonçalves, Fernanda Cury, Margarida Damasceno, Rui M. Reis and Olga Martinho
Glioblastoma multiforme (GBM) is the most aggressive malignant primary
brain tumor in adults with a very poor prognosis. The standard treatment for newly
diagnosed glioblastoma is surgical debulking followed by radiotherapy and
temozolomide (TMZ) with additional maintenance with TMZ. However, this regimen
offers modest benefits with a median survival of less than 15 months, with an
GBM is one of the most vascularized tumors; therefore antiangiogenic therapeutic
strategies are very appealing. Bevacizumab, a humanized monoclonal antibody against
vascular endothelial growth factor A, was the first FDA approved angiogenesis
inhibitor, based on impressive response rates in recurrent GBM. Recent trials have
shown that the combination of bevacizumab with standard radiotherapy–TMZ for the
treatment of newly diagnosed glioblastoma resulted in improved median progressionfree
survival, without gain in overall survival. Data regarding quality of life and
functional status are conflicting. Not surprisingly, there was an increase in adverse events associated with bevacizumab therapy, namely thrombosis, bleeding and
hypertension. Therefore, the efficacy of antiangiogenic therapy in the management of
GBM remains unclear. To improve outcomes, it has been made a huge effort to better
understand the biology underlying angiogenesis and tumor survival, as well as the
mechanisms of antiangiogenic resistance in GBM.
Angiogenesis, Antiangiogenic, Bevacizumab, Biomarkers, Central
nervous system, Glioblastoma, Glioma, Quality of life, Resistance, Response,
Safety, Survival, VEGF.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.