Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges

Gazanfar Rahmathulla,¹ Elizabeth J Hovey,^2,3 Neda Hashemi-Sadraei,⁴ Manmeet S Ahluwalia<sup>4

1</sup>Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, ²Department of Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia; ³School of Medicine, University of New South Wales, Sydney, NSW, Australia; ⁴Department of Medical Oncology, Neurological and Taussig Cancer Institutes, Cleveland Clinic, Cleveland, OH, USA

Abstract: High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV) are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas.

Keywords: bevacizumab, antiangiogenesis, glioma, glioblastoma, vascular endothelial growth factor