University of Lille, U-1192, F-59000, Lille, France; Inserm, U-1192, F-59000, Lille, France; CHU Lille, General and Stereotaxic Neurosurgery Service, F-59000, Lille, France; Department of Neurology & Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.
EORTC Headquarters, Brussels, Belgium.
Eur J Cancer. 2018 Sep;101:95-104. doi: 10.1016/j.ejca.2018.06.029. Epub 2018 Jul 20.
To test the hypothesis that despite bleeding risk, anticoagulants improve the outcome in glioblastoma because of reduced incidence of venous thromboembolic events and modulation of angiogenesis, infiltration and invasion.
We assessed survival associations of anticoagulant use from baseline up to the start of temozolomide chemoradiotherapy (TMZ/RT) (period I) and from there to the start of maintenance TMZ chemotherapy (period II) by pooling data of three randomised clinical trials in newly diagnosed glioblastoma including 1273 patients. Progression-free survival (PFS) and overall survival (OS) were compared between patients with anticoagulant use versus no use; therapeutic versus prophylactic versus no use; different durations of anticoagulant use versus no use; anticoagulant use versus use of anti-platelet agents versus neither anticoagulant nor anti-platelet agent use. Cox regression models were stratified by trial and adjusted for baseline prognostic factors.
Anticoagulant use was documented in 75 patients (5.9%) in period I and in 104 patients (10.2%) in period II. Anticoagulant use during period II, but not period I, was associated with inferior OS than no use on multivariate analysis (p = 0.001, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.18-1.95). No decrease in OS became apparent when only patients with prophylactic anticoagulant use were considered. No survival association was established for anti-platelet agent use.
Anticoagulant use was not associated with improved OS. Anticoagulants may not exert relevant anti-tumour properties in glioblastoma.
为了检验以下假说,即尽管存在出血风险,但抗凝剂通过降低静脉血栓栓塞事件的发生率、调节血管生成、浸润和转移,从而改善胶质母细胞瘤患者的预后。
我们评估了 3 项随机临床试验中从确诊胶质母细胞瘤开始到替莫唑胺放化疗(TMZ/RT)开始(I 期)和从那时到维持替莫唑胺化疗开始(II 期)期间抗凝剂使用与生存的相关性,共纳入 1273 例患者。比较抗凝剂使用与未使用患者、治疗性与预防性与未使用患者、不同抗凝剂使用时间与未使用患者、抗凝剂与抗血小板药物使用与未同时使用抗凝剂和抗血小板药物患者的无进展生存期(PFS)和总生存期(OS)。Cox 回归模型按试验分层,并根据基线预后因素进行调整。
I 期有 75 例(5.9%)患者和 II 期有 104 例(10.2%)患者记录了抗凝剂的使用。多变量分析显示,仅在 II 期而不是 I 期使用抗凝剂与未使用抗凝剂相比,OS 更差(p=0.001,风险比 [HR]为 1.52,95%置信区间 [CI]:1.18-1.95)。当仅考虑预防性抗凝剂使用的患者时,未观察到 OS 降低。抗血小板药物使用与 OS 无关。
抗凝剂的使用与 OS 改善无关。抗凝剂可能对胶质母细胞瘤没有明显的抗肿瘤作用。