Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

Background: Epilepsy is one of the most common symptoms of brain tumors. It is often drug resistant and generally worsen patients' quality of life (QoL). Brain tumors release glutamate among other mediators, contributing to seizures onset, and this is accompanied by an increased AMPA receptors' expression on neuronal cells' membrane. Perampanel (PER) is a relatively new antiseizure medication (ASM) that acts as a selective non-competitive AMPA receptors' antagonist. Given its mechanism of action, we aimed to evaluate through a prospective, observational study, the efficacy and safety of PER as an add-on treatment in patients with brain tumor-related epilepsy (BTRE). The study was called PERADET. Methods: Thirty-six adult patients (intention to treat population-ITT) affected by BTRE, with uncontrolled focal-onset seizures treated with 1–3 ASMs were recruited from four Italian epilepsy centers. Perampanel was added-on, titrated from 2 mg/day up to a maximum of 12 mg/day. Tumor history and therapy, type, and seizures frequency, previous ASMs were collected at 6 and 12 months. A battery of QoL tests were administered at baseline, 6 and 12 months. The primary endpoint was to assess the efficacy of PER by calculating the percent change in seizure frequency and the responder rate. The secondary endpoints were tolerability, retention rate at 12 months, and improvement in quality of life. Results: At the end of 12 months, 21 patients (per protocol population-PP) were available for evaluation. In this population the responder rate (percentage of patients who experienced a 50% or greater reduction in seizure frequency) was 90.4 with 33.3% of patients being seizure-free. In the ITT group the responder rate at the end of 12 months was 66.6 with 25% of patients being seizure free. PER was well tolerated (30.6% of patients experienced an adverse event, none was severe; three needed a treatment interruptions). Conclusions: Our study indicate that PER may be efficacious against BTRE as suggested by its mechanism of action and our current knowledge on mechanisms of brain tumor epileptogenicity. Trial Registration Number (TRN): (Prot. n° 0008872.25-06-2019); RS 919/17

Levetiracetam therapy in patients with brain tumour and epilepsy

Epilepsy is a common clinical problem in patients with brain tumours, strongly affecting patients\u2019 quality of life. Tumour-related seizures are often difficult to control, and the clinical picture is complicated by frequent interactions between antiepileptic drugs (AEDs) and antineoplastic agents. We studied the safety and efficacy of levetiracetam (LEV), a new AED with a different pharmacological profile from traditional anticonvulsants, in 19 patients (6 females; age range 28\u201370 years, mean 48 years) with supratentorial gliomas and epilepsy. Seizure types were simple partial in four patients, complex partial in 4, complex partial with secondary generalization in 7, and generalized tonic-clonic in 4. LEV was added to the existing AED treatment on account of persisting seizures, and titrated at dosages of 1,000\u20133,000 mg/day. Patients were seen at the Outpatient\u2019s Centre every 1\u20133 months, and followed-up for 7\u201350 months (mean 25 months, median 20 months). At the end of the observation period, nine patients were seizure free (seizure free period ranging from 7 to 33 months, mean 16, median 12) and five patients reported an improvement in seizure-frequency from daily to weekly (n = 1) or from weekly to monthly (n = 3). Seizure frequency was unmodified in four patients and increased (from monthly to weekly) in one. No LEVrelated adverse effects were observed. LEV plasma concentrations monitored in 12 subjects ranged from 11.9 to 82.1 lg/ml. Our preliminary open data indicate that add-on treatment with LEV in patients with brain tumours is safe and appears to be effective in reducing seizure frequency. Controlled studies on larger populations are warranted to confirm these open observations