Abstract：
BACKGROUND: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome.
METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors.
RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862).
CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.
METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors.
RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862).
CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.
摘要：
背景：关于抗癫痫药（AEDs）作为放射或化学增敏剂改善胶质母细胞瘤患者生存率的证据正在出现，但并不一致。我们进行了一项全国性的基于人群的研究，以评估术后放化疗期间并发AED对预后的影响。
方法：2008-2015年，国家健康保险研究数据库和癌症登记处共确定了1057例胶质母细胞瘤患者。符合条件的标准包括接受手术的人，辅助放疗和替莫唑胺，没有其他癌症诊断。比较放化疗期间同时服用AED14天或更长时间的患者（AED组）和未服用AED的患者（非AED组）之间的生存率，以及对丙戊酸（VPA）患者的亚组分析，左乙拉西坦（LEV），或苯妥英进行。多变量分析用于校正混杂因素。
结果：AED组642例，而非AED组的415。人口统计学数据是平衡的，除了AED组中更多的患者有AED的既往用药史（22.6%vs.18%,P0.078)。总的来说,与非AED组相比,AED组的死亡风险显著增加(HR=1.18,P0.016).此外,在AED组中也证实了对生存的不良剂量依赖性关系(HR=1.118,P0.0003).在亚组分析中，在VPA组（HR=1.29，P0.0002），但不在LEV(HR=1.18,P0.079)和苯妥英(HR=0.98,P0.862)中。
结论：在放化疗期间并发AED的患者未观察到生存改善。我们的实际数据不支持胶质母细胞瘤患者预防性使用AED。
方法：2008-2015年，国家健康保险研究数据库和癌症登记处共确定了1057例胶质母细胞瘤患者。符合条件的标准包括接受手术的人，辅助放疗和替莫唑胺，没有其他癌症诊断。比较放化疗期间同时服用AED14天或更长时间的患者（AED组）和未服用AED的患者（非AED组）之间的生存率，以及对丙戊酸（VPA）患者的亚组分析，左乙拉西坦（LEV），或苯妥英进行。多变量分析用于校正混杂因素。
结果：AED组642例，而非AED组的415。人口统计学数据是平衡的，除了AED组中更多的患者有AED的既往用药史（22.6%vs.18%,P0.078)。总的来说,与非AED组相比,AED组的死亡风险显著增加(HR=1.18,P0.016).此外,在AED组中也证实了对生存的不良剂量依赖性关系(HR=1.118,P0.0003).在亚组分析中，在VPA组（HR=1.29，P0.0002），但不在LEV(HR=1.18,P0.079)和苯妥英(HR=0.98,P0.862)中。
结论：在放化疗期间并发AED的患者未观察到生存改善。我们的实际数据不支持胶质母细胞瘤患者预防性使用AED。
