Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland (A.O.R., J.N., R.S.); Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland (S.J.); Department of Neurology, Universitätspital Zürich, Zurich, Switzerland (P.R., M.W.).
Neuro Oncol. 2014 Apr;16(4):584-8. doi: 10.1093/neuonc/not170. Epub 2013 Dec 4.
In patients with brain tumors, the choice of antiepileptic medication is guided by tolerability and pharmacokinetic interactions. This study investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non-enzyme-inducing agents, in this setting.
In this pragmatic, randomized, unblinded phase II trial (NCT00629889), patients with primary brain tumors and epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability were assessed using structured questionnaires. The primary composite endpoint was the need to discontinue the study drug, add-on of a further antiepileptic treatment, or occurrence of at least 2 seizures with impaired consciousness during 1 year follow-up.
Over 40 months, 25 patients were randomized to LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue: side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor progression.
This study shows that LEV and PGB represent valuable monotherapy options in this setting, with very good antiepileptic efficacy and an acceptable tolerability profile, and provides important data for the design of a phase III trial.
在脑肿瘤患者中，抗癫痫药物的选择取决于药物的耐受性和药代动力学相互作用。本研究旨在研究非酶诱导剂左乙拉西坦（LEV）和普瑞巴林（PGB）在这种情况下的有效性。
在这项实用、随机、非盲的 II 期试验（NCT00629889）中，原发性脑肿瘤合并癫痫患者被滴定至 LEV 或 PGB 的单药治疗。采用结构化问卷评估疗效和耐受性。主要复合终点是需要停用研究药物、添加另一种抗癫痫药物治疗或在 1 年随访期间发生至少 2 次意识障碍性癫痫发作。
在 40 个月的时间里，25 例患者被随机分配至 LEV 组，27 例患者被随机分配至 PGB 组。大多数患者为中年男性，患有高级别肿瘤且至少有一次全身性惊厥。LEV 组的平均日剂量为 1125mg，PGB 组为 294mg。LEV 组的保留率为 59%，PGB 组为 41%。LEV 组有 9 例和 PGB 组有 12 例患者达到复合终点，需要停药的原因分别为：副作用 6 例（LEV 组 3 例，PGB 组 3 例）、疗效不佳 1 例（LEV 组）、口服困难 0 例（LEV 组）、2 例（PGB 组）、添加另一种药物 1 例（LEV 组）和意识障碍性癫痫发作 1 例（LEV 组）。有 7 例 LEV 组和 5 例 PGB 组患者因肿瘤进展而死亡。
本研究表明，LEV 和 PGB 是这种情况下有价值的单药治疗选择，具有很好的抗癫痫疗效和可接受的耐受性，为 III 期临床试验的设计提供了重要数据。
