Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA.
Neuro Oncol. 2013 Apr;15(4):490-6. doi: 10.1093/neuonc/nos322. Epub 2013 Jan 17.
The signal transduction pathways of epidermal growth factor receptor and Ras are both important in the growth of glioblastoma multiforme (GBM). We hypothesized that inhibition of both pathways would improve the survival time of patients with recurrent GBM.
Patients with recurrent/progressive GBM with 0-2 prior chemotherapy regimens received erlotinib 150 mg once daily and sorafenib 400 mg twice daily until progression. The primary endpoint was overall survival. Pharmacokinetic sampling was performed during cycle 1.
The median overall survival was 5.7 months. Progression-free survival at 6 months was 14%. Toxicity was manageable. Clearance of erlotinib was markedly enhanced by sorafenib.
The study did not meet its objective of a 30% increase in overall survival time compared with historical controls. Erlotinib and sorafenib have significant pharmacokinetic interactions that may negatively impact the efficacy of the combination regimen.
表皮生长因子受体和 Ras 的信号转导通路在多形性胶质母细胞瘤（GBM）的生长中都很重要。我们假设抑制这两条通路将改善复发性 GBM 患者的生存时间。
接受过 0-2 种化疗方案的复发性/进行性 GBM 患者每日接受厄洛替尼 150mg 和索拉非尼 400mg 治疗，每日两次，直到疾病进展。主要终点是总生存期。在第 1 周期进行药代动力学采样。
中位总生存期为 5.7 个月。6 个月时无进展生存率为 14%。毒性可控制。索拉非尼显著增强厄洛替尼的清除率。
该研究未达到与历史对照相比总生存时间增加 30%的目标。厄洛替尼和索拉非尼具有显著的药代动力学相互作用，可能会降低联合治疗方案的疗效。
