Bevacizumab for the Treatment of Recurrent Glioblastoma

Abstract

Despite advances in upfront therapy, the prognosis in the great majority of patients with glioblastoma (GBM) is poor as almost all recur and result in disease-related death. Glioblastoma are highly vascularized cancers with elevated expression levels of vascular endothelial growth factor (VEGF), the dominant mediator of angiogenesis. A compelling biologic rationale, a need for improved therapy, and positive results from studies of bevacizumab in other cancers led to the evaluation of bevacizumab in the treatment of recurrent GBM. Bevacizumab, a humanized monoclonal antibody that targets VEGF, has been shown to improve patient outcomes in combination with chemotherapy (most commonly irinotecan) in recurrent GBM, and on the basis of positive results in two prospective phase 2 studies, bevacizumab was granted accelerated approval by the US Food and Drug Administration (FDA) as a single agent in recurrent GBM. Bevacizumab therapy is associated with manageable, class-specific toxicity as severe treatment-related adverse events are observed in only a minority of patients. With the goal of addressing questions and controversies regarding the optimal use of bevacizumab, the objective of this review is to provide a summary of the clinical efficacy and safety data of bevacizumab in patients with recurrent GBM, the practical issues surrounding the administration of bevacizumab, and ongoing investigations of bevacizumab in managing GBM.

Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

“…9 There have been several trials of angiogenic therapy applied to different places of cancer formation (breast, prostate, colon, liver, or kidney), [10][11][12][13][14] as well as in the brain. 15,16 Most utilize VEGF (VEGF-A and VEGF-B) or VEGF receptor (VEGFR1-3, PDGFRβ, and c-Kit) inhibition, [17][18][19][20] while some also block pathways not dependent on VEGF (CD36 receptor, FGF pathway, cyclooxygenase-2, and hypoxia-inducible factors 1α) [21][22][23] or inhibit endothelial cell migration (integrins αvβ1, αvβ3, αvβ5). 24 However, up to now, only bevacizumab, containing antiVEGF antibodies, has entered phase III clinical trials for treating GBM.…”

Local delivery of angiogenesis-inhibitor minocycline combined with radiotherapy and oral temozolomide chemotherapy in 9L glioma

“…6,7,26 Notably, when bevacizumab was first approved for the treatment of metastatic colorectal cancer in 2004, the approval was based on clinical trials that added bevacizumab to irinotecan, fluorouracil, and leucovorin. 13 In 2009, the US Food and Drug Administration approved bevacizumab for the treatment of glioblastoma.…”

The Acute Physiological Effects of the Vaso-Active Drug, L-NNA, a Nitric Oxide Synthase Inhibitor, on Renal and Tumour Perfusion in Human Subjects

“…This is achieved directly by nitric oxide activating guanylate cyclase to produce cyclic guanosine monophosphate (cGMP), which in turn triggers cGMP dependent protein kinases to promote myosin phosphorylation. Indirectly, NO also interacts with Vascular Endothelial Growth Factor (VEGF), another important vaso-active signalling agent, inhibition of which has shown activity against a range of tumours [13][14][15][16][17]. Expression of nitric oxide synthase (NOS), which catalyses the conversion of L-arginine into nitric oxide, is up-regulated by VEGF [18,19], whilst VEGF expression is down-regulated by nitric oxide [20].…”