Nagane Motoo
Dept. of Neurosurgery, Kyorin University Faculty of Medicine.
Gan To Kagaku Ryoho. 2014 Feb;41(2):141-7.
Glioblastoma(GBM)is the most malignant and frequent primary brain tumor. The current standard of care consists of maximum safe resection and radiotherapy with concomitant and subsequent temozolomide(TMZ)treatment. With this treatment plan, the prognosis of patients with GBM remains dismal, with a 5-year survival rate of<10%; thus development of effective, novel therapies is needed. Bevacizumab(Bev, Avastin®)is a humanized monoclonal antibody against vascular endothelial growth factor(VEGF), one of the major potent angiogenic factors for the growth of human cancers, including GBM. Bev has been shown to effectively shrink enhancing lesions of recurrent GBM and decrease symptom burden and brain edema. These positive results led to its approval for malignant glioma treatment in June 2013 in Japan. Two double-blind, placebo-controlled, randomized phase III studies of Bev in newly diagnosed GBM were conducted to verify its efficacy as a first-line therapy used in combination with TMZ. The results, which were reported at the American Society for Clinical Oncology(ASCO)meeting in June 2013, failed to show an increase in overall survival, despite prolongation in progression-free survival. These results led to many unsolved issues regarding the use of Bev for the treatment of GBM. We discuss these problems in this paper and highlight our institutional experience with Bev monotherapy for recurrent high-grade gliomas.
胶质母细胞瘤（GBM）是最恶性且最常见的原发性脑肿瘤。当前的标准治疗方案包括最大程度的安全切除以及放疗，并同时和后续使用替莫唑胺（TMZ）治疗。采用这种治疗方案，GBM患者的预后仍然很差，5年生存率<10%；因此需要开发有效的新型疗法。贝伐单抗（Bev，阿瓦斯汀®）是一种针对血管内皮生长因子（VEGF）的人源化单克隆抗体，VEGF是包括GBM在内的人类癌症生长的主要强效血管生成因子之一。已证明Bev能有效缩小复发性GBM的强化病灶，并减轻症状负担和脑水肿。这些积极结果使其于2013年6月在日本获批用于恶性胶质瘤治疗。开展了两项关于Bev用于新诊断GBM的双盲、安慰剂对照、随机III期研究，以验证其作为与TMZ联合使用的一线治疗的疗效。2013年6月在美国临床肿瘤学会（ASCO）会议上报告的结果显示，尽管无进展生存期有所延长，但总生存期并未增加。这些结果引发了许多关于使用Bev治疗GBM的未解决问题。我们在本文中讨论这些问题，并重点介绍我们机构使用Bev单药治疗复发性高级别胶质瘤的经验。
