Jeck Jennifer, Kassubek Rebecca, Coburger Jan, Edenhofer Simone, Schönsteiner Stefan S, Ludolph Albert C, Schmitz Bernd, Engelke Jens, Mayer-Steinacker Regine, Lewerenz Jan, Bullinger Lars
Department of Internal Medicine III, Ulm University Medical Centre, Ulm, Germany.
Department of Neurology, Ulm University and RKU - University and Rehabilitation Clinics Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Ther Adv Neurol Disord. 2018 Jan 21;11:1756285617753597. doi: 10.1177/1756285617753597. eCollection 2018.
Despite multidisciplinary treatment approaches, the prognosis for patients with high-grade glioma (HGG) is poor, with a median overall survival (OS) of 14.6 months for glioblastoma multiforme (GB). As high levels of vascular endothelial growth factor A (VEGF) are found in HGG, targeted anti-antiangiogenic therapy using the humanized monoclonal antibody bevacizumab (BEV) was studied in a series of clinical trials. Still, the discrepancy of BEV's efficacy with regard to initial clinical and radiological response and its reported failure to prolong survival remains to be explained. Here, we illustrate the effectiveness of BEV in recurrent HGG by summarizing our single-centre experience.
We have retrospectively investigated the effect of BEV in temozolomide refractory HGG in 39 patients treated at the University Hospital of Ulm, Germany.
Median duration of BEV treatment was 12.5 weeks; 23% of patients received BEV for more than 6 months and 15% for more than 1 year, until clinical or radiological tumour progression led to discontinuation. Furthermore, Karnofsky performance status increased in 30.6% and steroid dose decreased in 39% of all patients.
The review of literature reveals that phase II and III studies support BEV as an effective therapy in recurrent HGG, at least with regard to progression-free survival (PFS), but landmark phase III trials failed to prove benefit concerning OS. Here, we discuss reasons that may account for this observation. We conclude that prolonging PFS with maintenance of neurological function and personal and economic independency justifies the off-label use of BEV.
尽管采用了多学科治疗方法，但高级别胶质瘤（HGG）患者的预后仍然很差，多形性胶质母细胞瘤（GB）的中位总生存期（OS）为14.6个月。由于在HGG中发现血管内皮生长因子A（VEGF）水平较高，因此在一系列临床试验中研究了使用人源化单克隆抗体贝伐单抗（BEV）进行靶向抗血管生成治疗。然而，BEV在初始临床和放射学反应方面的疗效差异以及其未能延长生存期的报道仍有待解释。在此，我们通过总结我们的单中心经验来说明BEV在复发性HGG中的有效性。
我们回顾性研究了德国乌尔姆大学医院对39例接受替莫唑胺治疗无效的HGG患者使用BEV的效果。
BEV治疗的中位持续时间为12.5周；23%的患者接受BEV治疗超过6个月，15%的患者接受治疗超过1年，直到临床或放射学肿瘤进展导致停药。此外，所有患者中30.6%的卡氏评分提高且39%的患者类固醇剂量降低。
文献综述表明，II期和III期研究支持BEV作为复发性HGG的有效治疗方法，至少在无进展生存期（PFS）方面是如此，但具有里程碑意义的III期试验未能证明对OS有获益。在此，我们讨论可能解释这一观察结果的原因。我们得出结论，延长PFS并维持神经功能以及个人和经济独立性证明了BEV的超说明书使用是合理的。
