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贝伐单抗作为放疗、替莫唑胺和洛莫司汀治疗失败后胶质母细胞瘤的一线治疗药物。

Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine.

作者信息

Wenger Katharina J, Wagner Marlies, You Se-Jong, Franz Kea, Harter Patrick N, Burger Michael C, Voss Martin, Ronellenfitsch Michael W, Fokas Emmanouil, Steinbach Joachim P, Bähr Oliver

机构信息

University Hospital and University Cancer Center, German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt and German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.

Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, D-60528 Frankfurt, Germany.

出版信息

Oncol Lett. 2017 Jul;14(1):1141-1146. doi: 10.3892/ol.2017.6251. Epub 2017 May 25.

Abstract

In previous trials, bevacizumab failed to prolong the overall survival time in newly diagnosed glioblastoma and at the first recurrence. Randomized clinical trials at the second or further recurrence following the failure of radiotherapy, temozolomide and lomustine, and retrospective analyses focusing on this specific cohort, are not yet available. A total of 62 patients with glioblastoma who received bevacizumab after the failure of standard care, including radiotherapy, temozolomide and lomustine, were retrospectively identified. Patient characteristics, previous treatment details, concomitant therapy, response based on the Response Assessment in Neuro-Oncology criteria, and progression-free survival (PFS) and overall survival (OS) times and rates were evaluated. Furthermore, the PFS and OS times and rates were analyzed for responders and non-responders. Of the patients, 54.8% (n=34) responded to treatment [complete response (CR) 3.2%, n=2; partial response (PR) 51.6%, n=32]. The median PFS time was 3.5 months and the median OS time was 7.5 months. The PFS rate at 6 months was 21.5% and the OS rate at 12 months was 11.5%. Responders (CR or PR) experienced a superior median PFS time compared with non-responders (i.e. stable or progressive disease; 5.4 vs. 1.9 months; P<0.0001) and a superior PFS rate at 6 months (34.9 vs. 7.1%; P<0.0001). The median OS time (8.6 vs. 6.4 months; P<0.0001) and OS rate at 12 months (21.3 vs. 0%; P<0.0001) were also superior in patients who exhibited a response to bevacizumab treatment. In conclusion, the objective response rate and the PFS and OS times and rates indicate that bevacizumab has activity in patients with glioblastoma following the failure of radiotherapy, temozolomide, and lomustine. A randomized trial comparing bevacizumab with best supportive care in these patients is advised.

摘要

在先前的试验中,贝伐单抗未能延长新诊断胶质母细胞瘤及首次复发时的总生存时间。对于放疗、替莫唑胺和洛莫司汀治疗失败后的第二次或更晚期复发情况,尚无随机临床试验,也没有针对这一特定队列的回顾性分析。我们回顾性确定了62例在标准治疗(包括放疗、替莫唑胺和洛莫司汀)失败后接受贝伐单抗治疗的胶质母细胞瘤患者。评估了患者特征、既往治疗细节、伴随治疗、基于神经肿瘤学反应评估标准的反应情况、无进展生存期(PFS)和总生存期(OS)以及生存率。此外,还分析了反应者和无反应者的PFS和OS时间及生存率。在这些患者中,54.8%(n = 34)对治疗有反应[完全缓解(CR)3.2%,n = 2;部分缓解(PR)51.6%,n = 32]。中位PFS时间为3.5个月,中位OS时间为7.5个月。6个月时的PFS率为21.5%,12个月时的OS率为11.5%。与无反应者(即病情稳定或进展;5.4个月对1.9个月;P < 0.0001)相比,反应者(CR或PR)的中位PFS时间更长,6个月时的PFS率也更高(34.9%对7.1%;P < 0.0001)。对贝伐单抗治疗有反应的患者,其中位OS时间(8.6个月对6.4个月;P < 0.0001)和12个月时的OS率(21.3%对0%;P < 0.0001)也更高。总之,客观缓解率以及PFS和OS时间及生存率表明,贝伐单抗对放疗、替莫唑胺和洛莫司汀治疗失败后的胶质母细胞瘤患者有活性。建议在这些患者中开展一项比较贝伐单抗与最佳支持治疗的随机试验。

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