Department of Neurology, Regensburg University Medical Center, Regensburg, Germany.
Wilhelm Sander-NeuroOncology Unit, Regensburg University Medical Center, Regensburg, Germany.
PLoS One. 2018 Dec 3;13(12):e0207858. doi: 10.1371/journal.pone.0207858. eCollection 2018.
High-grade glioma (HGG) is associated with a limited prognosis. Drug repurposing has become of increasing interest to improve standard therapy. Statins and NSAIDs inhibit glioma cell growth in vitro and in vivo, but data on statin and NSAID treatment in relation to survival of patients with HGG are sparse.
We performed multivariable adjusted Cox-regression analyses among 1,093 patients with HGG from a regional cancer registry to obtain Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression-free survival (PFS) according to treatment with statins or NSAIDs. Data on dose and duration of treatment was mostly lacking in our analysis, therefore we were not able to perform dose-response analyses.
Use of statins was unrelated to OS or PFS of glioma patients. Use of aspirin was associated with prolonged OS and PFS in patients with WHO grade III, but not WHO grade IV glioma. Use of other NSAIDs (diclofenac, ibuprofen) or non-NSAID analgesics (paracetamol) was mostly unrelated to survival of glioma patients. Use of selective COX-2 inhibitors and metamizol was related to inferior patient survival in parts of the analyses.
Use of statins or NSAIDS, including aspirin, was not associated with prolonged OS or PFS of patients with WHO grade IV glioma in our selected cohort. There was an indication for improved survival in patients with WHO grade III glioma using aspirin, but further studies are needed to confirm our first observation.
高级别胶质瘤(HGG)的预后有限。药物再利用已成为提高标准治疗的兴趣点。他汀类药物和 NSAIDs 可抑制体外和体内神经胶质瘤细胞的生长,但关于他汀类药物和 NSAIDs 治疗与 HGG 患者生存的相关数据却很少。
我们对来自区域癌症登记处的 1093 名 HGG 患者进行了多变量调整 Cox 回归分析,以获得总体生存率(OS)和无进展生存率(PFS)的风险比(HR)和 95%置信区间(CI),这些患者根据他汀类药物或 NSAIDs 的治疗情况进行了分层。在我们的分析中,关于剂量和治疗时间的数据大多缺乏,因此我们无法进行剂量反应分析。
他汀类药物的使用与胶质瘤患者的 OS 或 PFS 无关。阿司匹林的使用与 WHO 分级 III 级但不是 WHO 分级 IV 级的胶质瘤患者的 OS 和 PFS 延长有关。其他 NSAIDs(双氯芬酸、布洛芬)或非 NSAID 类镇痛药(扑热息痛)的使用与胶质瘤患者的生存大多无关。选择性 COX-2 抑制剂和甲灭酸的使用在部分分析中与患者生存较差有关。
在我们选择的队列中,他汀类药物或 NSAIDs(包括阿司匹林)的使用与 WHO 分级 IV 级胶质瘤患者的 OS 或 PFS 延长无关。阿司匹林的使用可使 WHO 分级 III 级胶质瘤患者的生存得到改善,但需要进一步研究来证实我们的初步观察。