Bevacizumab for recurrent malignant gliomas - Efficacy, toxicity, and patterns of recurrence
Bevacizumab for recurrent malignant gliomas - Efficacy, toxicity, and patterns of recurrence
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DOI：
10.1212/01.wnl.0000304121.57857.38
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发表时间：
2008-03-04
期刊：
影响因子：
9.9
通讯作者：
Wen, P. Y.
中科院分区：
文献类型：
--
作者：
Norden, A. D.;Young, G. S.;Wen, P. Y.
背景：贝伐珠单抗是一种抗血管内皮生长因子的人源化单克隆抗体，可能对复发性恶性神经胶质瘤具有活性。复发时，一些患者似乎出现非增强性浸润性疾病，而不是肿瘤增强。方法：我们回顾性回顾了 55 名连续接受贝伐珠单抗和化疗的复发性恶性神经胶质瘤患者，以确定疗效、毒性和复发模式。使用盲法、标准化影像学检查和定量体积分析，将接受贝伐珠单抗治疗的患者的复发模式与 19 名仅接受化疗的患者的复发模式进行比较。结果：总共 2.3% 的患者获得完全缓解，31.8% 部分缓解，29.5% 最小缓解，29.5% 疾病稳定。放射学进展的中位时间为 19.3 周。胶质母细胞瘤患者的 6 个月无进展生存期 (PFS) 为 42%，间变性胶质瘤患者为 32%。在 23 名初始治疗出现进展的患者中，继续使用贝伐珠单抗并改变同步化疗药物。在任何情况下，这种变化都不会产生放射学反应，但两名患者的 PFS 延长至 20 周和 31 周。复发模式分析发现，贝伐珠单抗应答者的浸润性肿瘤体积相对于增强型肿瘤显着增加。结论：贝伐珠单抗和化疗的联合治疗耐受性良好，并且对复发性恶性神经胶质瘤有效。复发时，继续使用贝伐珠单抗并更换化疗药物仅对一小部分患者提供了长期的疾病控制。贝伐单抗可以通过比抑制非增强性浸润性肿瘤生长更有效地抑制增强性肿瘤复发来改变恶性神经胶质瘤的复发模式。
Background: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor.Methods: We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone.Results: A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders.Conclusions: Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth.