Duerinck J, Du Four S, Vandervorst F, D'Haene N, Le Mercier M, Michotte A, Van Binst A M, Everaert H, Salmon I, Bouttens F, Verschaeve V, Neyns B
Department of Medical Oncology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium.
Department of Neurosurgery, Universitair Ziekenhuis Brussel, Brussels, Belgium.
J Neurooncol. 2016 May;128(1):147-155. doi: 10.1007/s11060-016-2092-2. Epub 2016 Mar 2.
We conducted a randomized, non-comparative, multi center, phase II clinical trial in order to investigate the efficacy of axitinib, an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the vascular endothelial growth factor receptors, in patients with recurrent glioblastoma following prior treatment with radiation and temozolomide. Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or "physicians best alternative choice of therapy" that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint. The estimated 6-month progression-free survival rate was 34 % (95 % CI 14-54) for patients treated with axitinib and 28 % (95 % CI 8-48) with best alternative treatment; median overall survival was 29 and 17 weeks, respectively. Objective responses according to RANO criteria were documented in 28 % of patients treated with axitinib and 23 % of patients treated with best alternative therapy. A decrease in maximal uptake of 18F-fluoro-ethyL-tyrosine (18F-FET) by the glioblastoma on PET imaging was documented in 85 % of patients at the time of response on axitinib. Corticosteroid treatment could be stopped in four and tapered in seven out of the 15 patients who were treated with steroids at baseline in the axitinib cohort. Most frequent axitinib related grade ≥3 adverse events consisted of fatigue (9 %), diarrhea (9 %), and oral hyperesthesia (4.5 %). We conclude that axitinib has single-agent clinical activity and a manageable toxicity profile in patients with recurrent glioblastoma.
我们开展了一项随机、非对照、多中心的II期临床试验，以研究阿昔替尼（一种对血管内皮生长因子受体具有高亲和力和特异性的口服小分子酪氨酸激酶抑制剂）对接受过放疗和替莫唑胺治疗的复发性胶质母细胞瘤患者的疗效。44例患者被随机分配接受阿昔替尼治疗（起始剂量5mg，每日两次；N = 22）或“医生最佳替代治疗选择”，后者包括贝伐单抗（N = 20）或洛莫司汀（N = 2）。六个月无进展生存期作为主要终点。接受阿昔替尼治疗的患者估计六个月无进展生存率为34%（95%CI 14 - 54），接受最佳替代治疗的患者为28%（95%CI 8 - 48）；中位总生存期分别为29周和17周。根据RANO标准记录的客观缓解情况，在接受阿昔替尼治疗的患者中有28%，在接受最佳替代治疗的患者中有23%。在接受阿昔替尼治疗出现缓解时，85%的患者PET成像显示胶质母细胞瘤对18F - 氟乙基酪氨酸（18F - FET）的最大摄取量降低。在阿昔替尼队列中，基线时接受类固醇治疗的15例患者中，有4例可以停用皮质类固醇治疗，7例可以减量。与阿昔替尼相关的最常见≥3级不良事件包括疲劳（9%）、腹泻（9%）和口腔感觉过敏（4.5%）。我们得出结论，阿昔替尼对复发性胶质母细胞瘤患者具有单药临床活性且毒性特征可控。
