Perampanel in brain tumor-related epilepsy: Observational pilot study.

Silvana Zannino,Veronica Villani,Andrea Maialetti,Tatiana Koudriavtseva,Diana Giannarelli,Marta Maschio,Alessia Zarabla

doi:10.1002/brb3.1612

Silvana Zannino, Veronica Villani + Show 5 more

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https://doi.org/10.1002/brb3.1612

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Abstract

ObjectivePossible loss of efficacy and potential interactions between antiepileptic drugs (AEDs) and chemotherapy could complicate the management of patients with brain tumor‐related epilepsy (BTRE) that may expose patients to an increased risk of adverse events. Perampanel (PER) is a highly selective, noncompetitive, alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA)‐type glutamate receptor antagonist. This study evaluates the effectiveness, QoL, cognition, and mood of PER in add‐on therapy in BTRE patients.Material and MethodsObservational pilot study on the effectiveness of PER as add‐on therapy in BTRE patients with uncontrolled seizures with a 6‐month follow‐up.ResultsWe recruited 26 BTRE patients. During the follow‐up, 16 underwent chemotherapy and 11 radiotherapy; 11 had disease progression. Five patients dropped out. Mean daily PER dosage was 6.6 mg in the 21 patients who completed the follow‐up and 6.4 mg in the ITT population. The mean number of seizures/month decreased from 10.8 ± 15.03 at baseline to 1.7 ± 4.34 in the 21 patients who reached the final follow‐up. Responder rate was 88.4%: Eight patients were seizure‐free, 15 had ≥50% seizure reduction, and 3 remained stable. Four patients (15.4%) reported AEs: 2 required PER dose reduction, and 2 dropped out. Neuropsychological, mood, and QoL questionnaires were not statistically different compared to baseline. There were no significant differences in seizure control in patients with/without IDH1 mutation and with/without MGMT methylation.ConclusionsPerampanel proved to be effective on seizure control in BRTE patients and to be well tolerated without negative effects on cognition and QoL. Perampanel could be a valid therapeutic option in BTRE.

Highlights

In patients with brain tumor, epilepsy represents one of the most important symptoms
Objective: Possible loss of efficacy and potential interactions between antiepileptic drugs (AEDs) and chemotherapy could complicate the management of patients with brain tumor-related epilepsy (BTRE) that may expose patients to an increased risk of adverse events
Perampanel proved to be effective on seizure control in BRTE patients and to be well tolerated without negative effects on cognition and QoL

Summary

Introduction

In patients with brain tumor, epilepsy represents one of the most important symptoms. It has been estimated that seizures occur in rates varying from 20% to 40% of patients with brain tumors; seizures are the onset symptoms in a significant proportion of cases (Maschio et al, 2014; Perucca, 2013; Van Breemen, Wilms, & Vecht, 2007). 10% of patients with brain tumor do not have seizures as first symptom, but develop seizures at a later stage (Maschio, 2012). Brain tumor-related epilepsy (BTRE) patients may have an increase of adverse event due to a possible interaction with antiepileptic drugs (AEDs) and anticancer therapies (Perucca, 2013). The selection of the appropriate AED therapy in BTRE patients should be driven by multiple factors, which include efficacy in the specific type of seizure to be treated, and tolerability and drug-interaction potential

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