Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent malignant glioma
Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent malignant glioma
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DOI：
10.1007/s11060-013-1356-3
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发表时间：
2014-03-01
影响因子：
3.9
通讯作者：
Wick, Antje
中科院分区：
文献类型：
--
作者：
Wiestler, Benedikt;Radbruch, Alexander;Wick, Antje
对单克隆VEGF-A抗体贝伐单抗的研究提出了一些问题，如缺乏总体生存获益，疾病过程中的最佳时机以及潜在的联合和挽救治疗。我们回顾性评估了42例复发性恶性胶质瘤患者连续接受贝伐单抗和亚硝基脲治疗的生存率、放射学进展类型和补救性治疗的疗效。15例患者在进展阶段接受贝伐单抗治疗，随后接受亚硝基脲治疗，27例患者反之。治疗失败的时间，定义为从一种治疗开始到另一种治疗失败的时间，两组相似（9.6个月对9.2个月，log rank p = 0.19）。两组亚硝基源药物的无进展生存期相当，而贝伐单抗组的无进展生存期更长（5.3个月对4.1个月，log rank p = 0.03）。III级（n = 9）和IV级（n = 33）肿瘤患者的生存时间相似。出现对比增强T1进展的患者使用贝伐单抗的无进展生存期比出现非增强T2进展的患者更长。然而，贝伐单抗失败后的进展后生存时间没有差异。在这个系列中，早期使用贝伐单抗治疗与更好的结果没有关联。贝伐单抗早期治疗与晚期治疗相比，并没有导致治疗失败的不同时间，这一事实突出了贝伐单抗一线或复发试验的挑战，以证明如果在进展后发生贝伐单抗-na < ve患者的交叉治疗，总体生存获益。
Studies on the monoclonal VEGF-A antibody bevacizumab gave raise to questions regarding the lack of an overall survival benefit, the optimal timing in the disease course and potential combination and salvage therapies. We retrospectively assessed survival, radiological progression type on bevacizumab and efficacy of salvage therapies in 42 patients with recurrent malignant gliomas who received bevacizumab and nitrosourea sequentially. 15 patients received bevacizumab followed by nitrosourea at progression and 27 patients vice versa. Time to treatment failure, defined as time from initiation of one to failure of the other treatment, was similar in both groups (9.6 vs. 9.2 months, log rank p = 0.19). Progression-free survival on nitrosoureas was comparable in both groups, while progression-free survival on bevacizumab was longer in the group receiving bevacizumab first (5.3 vs. 4.1 months, log rank p = 0.03). Survival times were similar for patients with grade III (n = 9) and grade IV (n = 33) tumors. Progression-free survival on bevacizumab for patients developing contrast-enhancing T1 progression was longer than for patients who displayed a non-enhancing T2 progression. However, post-progression survival times after bevacizumab failure were not different. Earlier treatment with bevacizumab was not associated with better outcome in this series. The fact that earlier as compared to later bevacizumab treatment does not result in a different time to treatment failure highlights the challenge for first-line or recurrence trials with bevacizumab to demonstrate an overall survival benefit if crossover of bevacizumab-na < ve patients after progression occurs.