Retrospective analysis of the efficacy and tolerability of levetiracetam in patients with metastatic brain tumors

Abstract

Seizures are a common complication of metastatic brain tumors (MBT), affecting approximately 27-50% of all patients during the course of their illness. Treatment of tumor-induced seizures is often inadequate with traditional antiepileptic drugs (AED) due to a variety of factors, including activation of glutamatergic NMDA receptors, alterations of neuronal input pathways, and tumor growth. Levetiracetam (LEV) is a 2nd generation non-enzyme inducing AED with a novel mechanism of action, binding to neuronal synaptic vesicle protein SV2A, that has been previously shown to reduce seizure activity in patients with primary brain tumors. Due to its unique mechanism of action, it has been postulated that LEV may also be effective in controlling seizures from MBT. A retrospective chart review was performed of all Neuro-Oncology Center patients with MBT who had received LEV for seizure control. Thirteen patients were reviewed with a median age of 55.1 years (range: 34-70). Six patients had breast cancer, five had lung cancer, and two had melanoma. LEV was used as an add-on AED in seven patients (54%) and as monotherapy in six patients (46%), with a median dose of 1,000 mg/day (range: 500-3,000). The baseline median seizure frequency was one ictal event every other day. After the addition of LEV, the median seizure frequency was reduced to 0 per week. The seizure frequency was reduced to less than 50% of the pre-LEV baseline in 100% of patients (P=0.0002, Sign test), with 10 patients (77%; confidence interval: 46-95%) noting complete seizure control. The most common adverse event was somnolence and headache, noted in 3 of 13 patients (23%). LEV was very effective and well tolerated in MBT patients with seizures and should be considered for add-on therapy or as a substitute AED for monotherapy.

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).…”

Zonisamide: Antiproliferative and Antioxidant Effects on C6 Glioma Cancer Cell Model

“…TAS are partially controlled with multiple and high doses of antiepileptic drugs [1] such as acetazolamide, phenobarbital, valproic acid, perampanel, zonisamide, gabapentin and levetiracetam [2,3]. Concerning metastatic tumors, treatment of levetiracetam reduced seizure frequency to more than 50% in all 13 patients [4]. Similar results were obtained from the use of valproic acid.…”

Seizures in Children with Brain Tumours — Epidemiology, Significance, Management, and Outcomes

“…Meanwhile, evidence continues to mount documenting both the effectiveness and safety of newer-generation AEDS, like levetiracetam, oxcarbazepine and pregabalin [152,[196][197][198][199][200][201][202][203][204]. Though direct comparisons against the older drugs are generally lacking, theoretical advantages include the lack of any effect on cytochrome P450, and the fact that these drugs generally target specific risk factors for tumour-induced seizures [81].…”