Rossi Jessica, Cavallieri Francesco, Bassi Maria Chiara, Biagini Giuseppe, Rizzi Romana, Russo Marco, Bondavalli Massimo, Iaccarino Corrado, Pavesi Giacomo, Cozzi Salvatore, Giaccherini Lucia, Najafi Masoumeh, Pisanello Anna, Valzania Franco
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Neurology Unit, Neuromotor & Rehabilitation Department, Azienda USL-IRCCS of Reggio Emilia, 42123 Reggio Emilia, Italy.
Biomedicines. 2023 Feb 21;11(3):651. doi: 10.3390/biomedicines11030651.
(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6-12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11-52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.
(1) 背景：癫痫是脑肿瘤患者常见的合并症，这些患者的癫痫发作往往耐药。目前的证据表明，肿瘤微环境中谷氨酸能活性过高可能促进癫痫发生，同时也有利于肿瘤生长和侵袭。选择性非竞争性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂吡仑帕奈（PER）已被证明对局灶性癫痫患者有效且耐受性良好。此外，临床前体外研究表明该药物具有潜在的抗肿瘤活性。在本系统评价中，总结了PER治疗脑肿瘤相关性癫痫（BTRE）的疗效和耐受性的临床证据。(2) 方法：检索了5个数据库和2个临床试验注册库，检索时间从建库至2022年12月。(3) 结果：纳入了7项研究和6项临床试验。样本量为8至36例患者，他们接受PER添加治疗（平均剂量为4至7毫克/天）用于BTRE。经过6至12个月的随访，缓解率（癫痫发作完全缓解或发作频率降低≥50%的患者百分比）为75%至95%，癫痫发作完全缓解率高达94%。关于耐受性，11%至52%的患者出现非严重不良反应（最常见的是头晕、眩晕、焦虑、易怒）。保留率为56%至83%。然而, 因不良事件停药的患者最多仅占12.5%。(4)结论：PER似乎对BTRE患者有效、安全且耐受性良好。应在更同质且更大规模的人群中开展进一步随机研究，同时评估PER对肿瘤进展、总生存期和无进展生存期的影响。
