Does the choice of antiepileptic drug affect survival in glioblastoma patients?
Does the choice of antiepileptic drug affect survival in glioblastoma patients?
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DOI：
10.1007/s11060-016-2191-0
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发表时间：
2016-09-01
影响因子：
3.9
通讯作者：
Owe, Jone F.
中科院分区：
文献类型：
--
作者：
Knudsen-Baas, Kristin M.;Engeland, Anders;Owe, Jone F.
胶质母细胞瘤（GBM）患者经常患有症状性癫痫。影响细胞色素 P450 酶系统的较旧抗癫痫药物 (AED) 已被广泛使用，但人们越来越关注与其他药物的相互作用。这项研究调查了酶作用很小或没有酶作用的新型 AED 是否越来越受欢迎。先前的研究表明丙戊酸可以提高 GBM 的生存率。我们研究了 AED 对 GBM 患者总生存率的影响。通过国家登记处的链接纳入了 2004 年至 2010 年挪威诊断的所有 GBM 患者，并对恶性肿瘤和药物使用的后续数据进行了分析。在多变量 Cox 比例风险回归中，AED 相互之间以及相关因素进行了调整。与时间相关的变量消除了不朽的时间偏差。研究人群为 1263 名经组织学证实的 GBM 患者。卡马西平是 2004 年至 2006 年间诊断为 GBM 的患者最常用的 AED，而左乙拉西坦则越来越多地用于后来诊断的患者。使用癫痫报销代码的 AED 对生存无益。六种 AED（丙戊酸、左乙拉西坦、卡马西平、奥卡西平、拉莫三嗪或苯妥英）均未显着改变总生存期。随着时间的推移，GBM 患者的 AED 处方已从较旧的 AED 转向较新的 AED。我们发现 GBM 患者无论是使用 AED 治疗癫痫，还是使用六种单独的 AED 都没有显着的生存获益。
Patients with glioblastoma (GBM) often suffer from symptomatic epilepsy. Older antiepileptic drugs (AEDs) which affect the enzyme system cytochrome P450 have been in extensive use, but there is an increasing focus on interactions with other drugs. This study investigated whether newer AEDs with little or no enzyme effect are increasingly preferred. Previous research has indicated that valproate improves survival in GBM. We investigated the impact of AEDs on overall survival in GBM patients. All GBM patients diagnosed in Norway 2004-2010 were included through a linkage of national registries, and follow-up data on the malignancy and drug usage were analyzed. In a multivariate cox proportional-hazards regression, AEDs were adjusted for each other and for relevant factors. Immortal time bias was eliminated with time-dependent variables. The study population was 1263 patients with histologically confirmed GBM. Carbamazepine was the most frequently prescribed AED to patients diagnosed with GBM during 2004-2006, while levetiracetam was increasingly prescribed to patients diagnosed later. Taking AEDs on a reimbursement code of epilepsy was not beneficial for survival. None of the six AEDs valproate, levetiracetam, carbamazepine, oxcarbazepine, lamotrigine or phenytoin significantly altered overall survival. There has been a shift in the prescriptions of AEDs to GBM patients from older to newer AEDs over time. We found no significant survival benefit in GBM patients neither from treatment with AEDs for epilepsy in general, nor from the usage of six separate AEDs.