Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.
J Neurooncol. 2018 May;138(1):163-171. doi: 10.1007/s11060-018-2786-8. Epub 2018 Feb 8.
Glioblastomas are malignant brain tumors with poor prognosis. Lately, data from clinical studies assessing the role of co-medications in different cancer types suggested reduced mortality and potential anti-tumor activity for statins, angiotensin-I converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (sartans). Here, we analysed the association of co-treatment with statins, ACEI or sartans with outcome in a cohort of 810 patients enrolled in the phase III CENTRIC and phase II CORE trials on the role of the integrin antagonist, cilengitide, in newly diagnosed glioblastoma with or without O-methylguanine DNA methyltransferase (MGMT) promoter methylation. Progression-free survival (PFS) and overall survival (OS) were analysed for each medication in the pooled patient group. No association was found for co-medication with either drug for PFS or OS. Median OS was 22.1 (statins) versus 22.2 (control) months (HR 1.06, 95% CI 0.81-1.39, p = 0.69), 20.4 (ACEI) versus 22.6 (control) months (HR 1.25, 95% CI 0.96-1.62, p = 0.10), and 21.7 (sartans) versus 22.3 (control) months (HR 0.86, 95% CI 0.61-1.21, p = 0.38). None of the comparisons showed a signal for different PFS or OS when analyses were controlled for MGMT promoter methylation or treatment group (TMZ/RT → TMZ vs. RT + CIL + TMZ → TMZ + CIL). This secondary analysis of two large glioblastoma trials thus was unable to detect evidence for an association of the use of statins, ACEI or sartans with outcome in patients with newly diagnosed glioblastoma. These data challenge the rationale for prospective studies on the possible role of these non-tumor-specific drugs within the concept of drug repurposing.
胶质母细胞瘤是预后不良的恶性脑肿瘤。最近，来自评估不同癌症类型联合用药作用的临床研究的数据表明，他汀类药物、血管紧张素转化酶抑制剂（ACEI）和血管紧张素 II 受体阻滞剂（沙坦类）可降低死亡率并具有潜在的抗肿瘤活性。在这里，我们分析了在接受整合素拮抗剂西仑吉肽治疗的 810 名新诊断的胶质母细胞瘤患者的 III 期 CENTRIC 和 II 期 CORE 试验中，联合使用他汀类药物、ACEI 或沙坦类药物与 O-甲基鸟嘌呤 DNA 甲基转移酶（MGMT）启动子甲基化的患者的结果之间的相关性。在合并患者组中分析了每种药物的无进展生存期（PFS）和总生存期（OS）。联合用药与 PFS 或 OS 均无相关性。中位 OS 为他汀类药物组 22.1 个月，对照组 22.2 个月（HR 1.06，95%CI 0.81-1.39，p=0.69），ACEI 组 20.4 个月，对照组 22.6 个月（HR 1.25，95%CI 0.96-1.62，p=0.10），沙坦类药物组 21.7 个月，对照组 22.3 个月（HR 0.86，95%CI 0.61-1.21，p=0.38）。当分析受 MGMT 启动子甲基化或治疗组（TMZ/RT→TMZ 与 RT+CIL+TMZ→TMZ+CIL）控制时，这些比较均未显示出不同的 PFS 或 OS 的信号。因此，这两项大型胶质母细胞瘤试验的二次分析未能检测到新诊断的胶质母细胞瘤患者使用他汀类药物、ACEI 或沙坦类药物与结局之间存在关联的证据。这些数据对前瞻性研究这些非肿瘤特异性药物在药物再利用概念中可能作用的合理性提出了挑战。
