Levetiracetam therapy in patients with brain tumour and epilepsy

Abstract

Epilepsy is a common clinical problem in patients with brain tumours, strongly affecting patients' 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 28-70 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 1,000-3,000 mg/day. Patients were seen at the Outpatient's Centre every 1-3 months, and followed-up for 7-50 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 LEV-related adverse effects were observed. LEV plasma concentrations monitored in 12 subjects ranged from 11.9 to 82.1 microg/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.

Brain tumor epilepsy: A reappraisal and six remaining issues to be debated

“…In a uncontrolled prospective study, LEV was shown to be well tolerated and provided a good seizure improvement in 17 patients with BTE (Usery, Michael et al, 2009). Further studies confirmed the good profile of LEV in BTE Rosati, Buttolo et al ;Maschio, Albani et al 2006;Newton, Goldlust et al 2006) and metastatic brain tumor epilepsy Newton, Dalton et al 2007). Several experts recommend use of LEV as first monotherapy in BTE Vecht and Wilms ;Vecht and van Breemen 2006;van Breemen, Rijsman et al 2009), although others still suggest valproic acid, lamotrigine and topiramate as first choice treatments (van Breemen, Wilms et al 2007).…”

Anticonvulsant prophylaxis for brain tumor surgery: determining the current best available evidence

“…52 A large number of smaller studies have also shown levetiracetam to be well tolerated in brain tumor patients, with somnolence or other behavioral side effects being the most common adverse events, 31,37,40,41,55,64 with adverse effects being mostly reversible with dose reduction or displacement. 31,34,67 Levetiracetam demonstrated significantly fewer adverse effects than phenytoin when AED prophylaxis was given for supratentorial surgery, along with statistically equal efficacy (1% vs 4.3% early seizure incidence). 37 In contrast, patients given phenytoin were more likely to experience adverse effects than a seizure (18% vs 4%), and were much less likely to remain on the medication 1 year after surgery than with levetiracetam (26% vs 64%).…”

Glioma-Associated Epilepsy

“…Several antiepileptic agents have appeared over the past two decades that have shown efficacy and greater tolerability in patients with brain tumour-related epilepsy [88][89][90][91][92]. The side effect profile of the traditional antiepileptic medications such as phenobarbital, phenytoin, carbamazepine and valproic acid was such [93,94,5,95] that it seemed often to take precedence over the desire to reduce seizure activity [96].…”