Department of Neurology and Neurological Surgery, University of Washington, Seattle, Washington, 98109, USA.
Cancer. 2010 Sep 1;116(17):3988-99. doi: 10.1002/cncr.25256.
Despite advances in adjuvant therapy, the prognosis for most patients with high-grade glioma (HGG) is poor, and almost all HGGs have a likelihood of disease recurrence. HGGs are highly vascularized tumors with elevated expression levels of vascular endothelial growth factor (VEGF), an important mediator of angiogenesis. A compelling biologic rationale, a pressing need for improved therapeutics and positive results from studies of bevacizumab in other tumor types, led to the evaluation of bevacizumab in the treatment of HGG. It was demonstrated previously that bevacizumab, which is a humanized monoclonal antibody that targets VEGF, improved outcomes when combined with chemotherapy (most commonly irinotecan) in patients with recurrent HGG; and, on the basis of an improved objective response rate in 2 prospective phase 2 studies, bevacizumab was granted accelerated approval by the US Food and Drug Administration as a single agent in patients with previously treated glioblastoma (GB). Bevacizumab-containing therapy has been associated with manageable, class-specific toxicity; however, severe treatment-related adverse events are observed in a minority of patients. Preliminary data on bevacizumab-based therapy in recurrent anaplastic gliomas, in the frontline treatment of GB, and in additional patient populations are also encouraging. With the goal of addressing unanswered questions regarding the optimal use of bevacizumab, the objective of the current review was to provide a summary of the clinical efficacy and safety data on bevacizumab in patients with HGG, the practical issues surrounding the administration of bevacizumab, and ongoing investigations of bevacizumab in additional brain tumor treatment settings.
尽管辅助治疗取得了进展，但大多数高级别胶质瘤（HGG）患者的预后仍然较差，几乎所有 HGG 都有可能复发。HGG 是高度血管化的肿瘤，血管内皮生长因子（VEGF）表达水平升高，VEGF 是血管生成的重要介质。强有力的生物学原理、对改善治疗方法的迫切需求以及贝伐珠单抗在其他肿瘤类型研究中的积极结果，促使人们评估贝伐珠单抗在 HGG 治疗中的应用。先前已经证明，贝伐珠单抗是一种针对 VEGF 的人源化单克隆抗体，与复发性 HGG 患者的化疗（最常见的是伊立替康）联合使用时，可以改善结局；并且，基于 2 项前瞻性 2 期研究中客观缓解率的提高，贝伐珠单抗作为单药被美国食品和药物管理局加速批准用于先前治疗过的胶质母细胞瘤（GB）患者。贝伐珠单抗联合治疗具有可管理的、特定于类别的毒性；然而，少数患者会出现严重的治疗相关不良事件。贝伐珠单抗在复发性间变性神经胶质瘤、GB 的一线治疗以及其他患者人群中的初步数据也令人鼓舞。为了解决贝伐珠单抗最佳使用方面的未决问题，本综述的目的是总结贝伐珠单抗在 HGG 患者中的临床疗效和安全性数据、贝伐珠单抗给药的实际问题以及贝伐珠单抗在其他脑肿瘤治疗环境中的正在进行的研究。
