Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
Neurology. 2011 Sep 20;77(12):1156-64. doi: 10.1212/WNL.0b013e31822f02e1. Epub 2011 Aug 31.
This analysis was performed to assess whether antiepileptic drugs (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients with newly diagnosed glioblastoma.
The European Organization for Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the impact of the interaction between AED use and chemoradiotherapy on survival. Data were adjusted for known prognostic factors.
When treatment began, 175 patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients without an AED or patients taking an EIAED only. The overall survival (OS) of patients who were receiving an AED at baseline vs not receiving any AED was similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95% CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).
VPA may be preferred over an EIAED in patients with glioblastoma who require an AED during TMZ-based chemoradiotherapy. Future studies are needed to determine whether VPA increases TMZ bioavailability or acts as an inhibitor of histone deacetylases and thereby sensitizes for radiochemotherapy in vivo.
本分析旨在评估抗癫痫药物（AEDs）是否调节新诊断胶质母细胞瘤患者替莫唑胺放化疗的疗效。
检查欧洲癌症研究与治疗组织（EORTC）26981-22981/加拿大国家癌症研究所（NCIC）CE.3 临床试验数据库中放疗（RT）联合或不联合替莫唑胺（TMZ）治疗新诊断胶质母细胞瘤，以评估 AED 使用与放化疗之间相互作用对生存的影响。数据针对已知预后因素进行了调整。
当治疗开始时，175 名患者（30.5%）无 AED，277 名患者（48.3%）服用任何酶诱导型 AED（EIAED），135 名患者（23.4%）服用任何非 EIAED。服用丙戊酸（VPA）的患者比无 AED 或仅服用 EIAED 的患者更容易出现 3/4 级血小板减少和白细胞减少。基线时接受 AED 治疗的患者的总生存（OS）与未接受任何 AED 治疗的患者相似。单独服用 VPA 的患者（97 [16.9%]）似乎从 TMZ/RT 中获得更多生存获益（风险比[HR]0.39，95%置信区间[CI]0.24-0.63），而仅服用 EIAED 的患者（252 [44%]）（HR 0.69，95% CI 0.53-0.90）或未接受任何 AED 的患者（HR 0.67，95% CI 0.49-0.93）。
在需要 TMZ 放化疗期间服用 AED 的胶质母细胞瘤患者中，VPA 可能优于 EIAED。需要进一步的研究来确定 VPA 是否增加 TMZ 的生物利用度，或作为组蛋白去乙酰化酶抑制剂，从而在体内增强放化疗的敏感性。
