Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA.
Cancer. 2010 Aug 1;116(15):3663-9. doi: 10.1002/cncr.25275.
The current study was conducted to evaluate the efficacy of sorafenib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, when added to standard radiotherapy and temozolomide in the first-line treatment of patients with glioblastoma multiforme.
After initial surgical resection or biopsy, patients with newly diagnosed glioblastoma multiforme received concurrent radiotherapy (2.0 grays [Gy]/day; total dose, 60 Gy) and temozolomide (at a dose of 75 mg/m2 orally daily), followed by 6 months of maintenance therapy with temozolomide (at a dose of 150 mg/m2 orally on Days 1-5 every 28 days) and sorafenib (at a dose of 400 mg orally twice daily). Patients were re-evaluated every 2 months; the primary endpoint of the trial was progression-free survival (PFS).
A total of 47 patients were treated; 34 had undergone previous debulking surgery. Nineteen patients withdrew from treatment before the initiation of maintenance therapy with temozolomide and sorafenib (12 because of early tumor progression). Twenty-eight patients (60% of enrolled patients) received 4 months of maintenance therapy with temozolomide and sorafenib, and 9 patients (19%) completed the planned 6 months of maintenance therapy. The median PFS for the entire group was 6 months (95% confidence interval [95% CI], 3.7-7 months), with a 1-year PFS rate of 16%. The median overall survival was 12 months (95%CI, 7.2-16 months). Maintenance therapy with temozolomide and sorafenib was found to be well tolerated by most patients, with no grade 3/4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) reported to occur in >10% of patients.
The addition of sorafenib did not appear to improve the efficacy of treatment when compared with the results expected with standard therapy. A substantial percentage of patients (40%) did not receive any maintenance sorafenib, most often because of early disease progression. The administration of angiogenesis inhibitors concurrently with radiotherapy and temozolomide may optimize the opportunity to improve therapy.
本研究旨在评估索拉非尼（一种口服血管内皮生长因子受体酪氨酸激酶抑制剂）在胶质母细胞瘤患者的一线治疗中联合标准放疗和替莫唑胺的疗效。
在初始手术切除或活检后，新诊断为胶质母细胞瘤的患者接受同步放疗（2.0 戈瑞[Gy]/天；总剂量 60 Gy）和替莫唑胺（剂量为 75mg/m2 口服，每天一次），然后接受 6 个月的替莫唑胺维持治疗（剂量为 150mg/m2 口服，每天一次，每 28 天一次）和索拉非尼（剂量为 400mg 口服，每天两次）。患者每 2 个月进行一次重新评估；试验的主要终点是无进展生存期（PFS）。
共治疗了 47 例患者；其中 34 例曾行减瘤手术。19 例患者在开始替莫唑胺和索拉非尼维持治疗前退出治疗（12 例因早期肿瘤进展）。28 例患者（纳入患者的 60%）接受了 4 个月的替莫唑胺和索拉非尼维持治疗，9 例患者（19%）完成了计划的 6 个月维持治疗。整个组的中位 PFS 为 6 个月（95%置信区间[95%CI]，3.7-7 个月），1 年 PFS 率为 16%。中位总生存期为 12 个月（95%CI，7.2-16 个月）。大多数患者对替莫唑胺和索拉非尼的维持治疗耐受性良好，未报告 10%以上患者出现 3/4 级毒性（根据国家癌症研究所常见毒性标准[版本 3.0]）。
与标准治疗的预期结果相比，添加索拉非尼似乎并未提高疗效。很大一部分患者（40%）未接受任何维持性索拉非尼治疗，最常见的原因是早期疾病进展。血管生成抑制剂与放疗和替莫唑胺同时给药可能优化改善治疗的机会。
