Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: analysis of single-agent and combined modality approaches.
Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: analysis of single-agent and combined modality approaches.
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DOI：
10.1186/1748-717x-6-2
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发表时间：
2011-01-07
期刊：
影响因子：
--
通讯作者：
Gutin PH
中科院分区：
文献类型：
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作者：
Beal K;Abrey LE;Gutin PH
新诊断的胶质母细胞瘤手术切除后放疗和替莫唑胺可以延长生存期，但不能治愈。对于一线治疗后疾病进展的患者，没有标准治疗，尽管可以使用进一步的手术，化疗和放疗。抗血管生成疗法可能适用于治疗胶质母细胞瘤，因为血管生成对肿瘤生长至关重要。在一项大型、非比较性II期试验中，在复发性胶质母细胞瘤患者中评估了贝伐珠单抗单药治疗和与伊立替康联合治疗;联合治疗的6个月无进展生存期（PFS）率估计为50.3%，中位总生存期为8.9个月，缓解率为37.8%。单药贝伐珠单抗也超过了挽救化疗的预定活性阈值（6个月PFS率，15%），实现了42.6%的6个月PFS率（p < 0.0001）。根据这些结果和另一项II期试验的结果，美国食品和药物管理局批准加速批准单药贝伐珠单抗治疗既往治疗后进展的胶质母细胞瘤。潜在的抗血管生成药物，如西仑吉肽和XL 184，在复发性胶质母细胞瘤中也显示出单一药物活性的证据。此外，在疾病进展时使用抗血管生成药物和放射治疗可能会提高单模态方法的治疗率。总体而言，这些药物似乎耐受性良好，不良事件特征与其他实体瘤研究中报告的相似。需要进一步的研究来确定抗血管生成治疗在一线治疗中的作用，并确定联合治疗的最佳方案和合作药物。
Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy.