Hainsworth John D, Shih Kent C, Shepard Gregg C, Tillinghast Guy W, Brinker Brett T, Spigel David R
Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA.
Clin Adv Hematol Oncol. 2012 Apr;10(4):240-6.
To evaluate the efficacy of adding bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, and everolimus, a mammalian target of rapamycin (mTOR inhibitor), to standard radiation therapy/temozolomide in the first-line treatment of patients with glioblastoma.
Following surgical resection or biopsy, patients with newly diagnosed glioblastoma received standard radiation therapy/temozolomide plus bevacizumab 10 mg/kg intravenously (IV) every 2 weeks. Four weeks after the completion of radiation therapy, patients began oral everolimus 10 mg daily, and continued bevacizumab every 2 weeks; therapy continued until tumor progression or unacceptable toxicity.
Sixty-eight patients were treated, 82% of whom had previously undergone partial or complete surgical resection. Sixty-four patients completed combined modality therapy, and 57 patients began maintenance therapy with bevacizumab/everolimus. Thirty-one of 51 patients (61%) with measurable tumor had objective responses. After a median follow-up of 17 months, the median progression-free survival (PFS) was 11.3 months (95% confidence interval [CI], 9.3-13.1 months); median overall survival was 13.9 months. Toxicity was consistent with the known toxicity profile of bevacizumab; grade 3/4 toxicities during maintenance therapy related to everolimus included fatigue (27%), pneumonitis (7%), and stomatitis (5%).
The use of bevacizumab and everolimus as part of first-line combined modality therapy for glioblastoma was feasible and efficacious. The PFS compared favorably to previous reports with standard radiation therapy/temozolomide therapy, and is similar to results achieved in other phase II trials in which bevacizumab was added to fist-line treatment. Ongoing randomized phase III trials will clarify the role of bevacizumab in this setting.
评估在胶质母细胞瘤一线治疗中，将血管内皮生长因子（VEGF）抑制剂贝伐单抗和雷帕霉素靶蛋白（mTOR）抑制剂依维莫司添加到标准放疗/替莫唑胺方案中的疗效。
新诊断的胶质母细胞瘤患者在手术切除或活检后，接受标准放疗/替莫唑胺，同时每2周静脉注射（IV）10 mg/kg贝伐单抗。放疗结束4周后，患者开始每日口服10 mg依维莫司，并继续每2周注射一次贝伐单抗；治疗持续至肿瘤进展或出现不可接受的毒性反应。
共治疗68例患者，其中82%曾接受过部分或完全手术切除。64例患者完成了综合治疗，57例患者开始接受贝伐单抗/依维莫司维持治疗。51例可测量肿瘤患者中有31例（61%）出现客观缓解。中位随访17个月后，无进展生存期（PFS）的中位数为11.3个月（95%置信区间[CI]，9.3 - 13.1个月）；总生存期中位数为13.9个月。毒性反应与贝伐单抗已知的毒性特征相符；维持治疗期间与依维莫司相关的3/4级毒性反应包括疲劳（27%）、肺炎（7%）和口腔炎（5%）。
将贝伐单抗和依维莫司作为胶质母细胞瘤一线综合治疗的一部分是可行且有效的。与之前标准放疗/替莫唑胺治疗的报告相比，PFS表现良好，与其他在一线治疗中添加贝伐单抗的II期试验结果相似。正在进行的随机III期试验将阐明贝伐单抗在此情况下的作用。
