Norden A D, Young G S, Setayesh K, Muzikansky A, Klufas R, Ross G L, Ciampa A S, Ebbeling L G, Levy B, Drappatz J, Kesari S, Wen P Y
Department of Neurology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, SW430B, 44 Binney St., Boston, MA 02115, USA.
Neurology. 2008 Mar 4;70(10):779-87. doi: 10.1212/01.wnl.0000304121.57857.38.
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.
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.
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.
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.
贝伐单抗是一种抗血管内皮生长因子的人源化单克隆抗体，可能对复发性恶性胶质瘤有活性。在复发时，一些患者似乎发展为无强化的浸润性疾病而非强化肿瘤。
我们回顾性分析了55例连续接受贝伐单抗和化疗的复发性恶性胶质瘤患者，以确定疗效、毒性和复发模式。通过盲法、标准化影像评估和定量容积分析，将接受贝伐单抗治疗患者的复发模式与19例单纯接受化疗患者的复发模式进行比较。
总共2.3%的患者有完全缓解，31.8%部分缓解，29.5%轻微缓解，29.5%病情稳定。影像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例初始治疗后病情进展的患者中，继续使用贝伐单抗并更换了同期化疗药物。无一例更换药物后产生影像学缓解，但有2例患者的PFS延长至20周和31周。复发模式分析显示，贝伐单抗治疗有反应的患者中，浸润性肿瘤体积相对于强化肿瘤显著增加。
贝伐单抗与化疗的联合治疗耐受性良好，对复发性恶性胶质瘤有活性。在复发时，继续使用贝伐单抗并更换化疗药物仅在一小部分患者中提供了长期疾病控制。贝伐单抗可能通过比抑制无强化的浸润性肿瘤生长更有效地抑制强化肿瘤复发，从而改变恶性胶质瘤的复发模式。
