The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

Abstract

Purpose Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. Methods In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. Results We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26–51%) versus 30% (95%CI 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. Conclusion Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

Prescription preferences of antiepileptic drugs in brain tumor patients: An international survey among EANO members

“…Commonly chosen alternatives to levetiracetam as equivalent first choice or when patients had experienced treatment failure on their first choice AED due to inefficacy or intolerable adverse effects included lacosamide (preferred in Austria, France, Italy, Spain, and Switzerland), lamotrigine (preferred in Germany and the United Kingdom), and valproic acid (preferred in the Netherlands). Lacosamide and lamotrigine showed similar effectiveness in diffuse gliomas in a recent retrospective observational study, 12 but high-quality comparative AED second-line studies in BTRE are currently lacking and these country-specific differences most probably reflect differing expert opinion per country and invites to conduct a comparative European randomized second-line AED study in BTRE. 13 …”

Brain tumor related epilepsy: pathophysiological approaches and rational management of antiseizure medication

“…The number of studies on lamotrigine in BTRE is very limited. In one retrospective study, the 12-months cumulative incidence of treatment failure had been 38% and the incidence of adverse events 17% with a second line lamotrigine monotherapy (which had been comparable to the alternative treatment with LCM in this study) [ 48 ]. Besides potential interaction with anti-tumor medication, disadvantages of LTG are its availability only as an oral formulation and the slow titration at initiation of the medication.…”

“…It is of note that before initiation of LCM an atrioventricular block of second or higher degree has to be excluded via electrocardiogram. A retrospective study in glioma patients, in which LTG (n = 61 patients) and LCM (n = 78 patients) were compared reported similar efficacy and a similar incidence of treatment failure due to adverse events for both ASMs [ 48 ].…”

Management of epilepsy in brain tumor patients

“…Instead of prescribing two subsequential AED monotherapies before combining AEDs, in BTRE there is a natural tendency towards AED duotherapy as second-line treatment [ ]. The duotherapy combination levetiracetam with valproic acid (n ¼ 236) showed better efficacy compared to other duotherapy combinations with either levetiracetam or valproic acid (n ¼ 119), while level of toxicity was similar [34 ]. Brivaracetam and perampanel are both relatively new AEDs and have both shown to be well tolerated and effective in reducing seizure frequency in BTRE patients as add-on, but sample sizes were small [38,39].…”

“…Ruda et al [ 36 ] conducted a prospective observational study in n = 93 brain tumor patients with epilepsy evaluating add-on lacosamide, which showed good efficacy and was generally well tolerated. (Add-on) lacosamide showed similar effectiveness compared to (add-on) lamotrigine in n = 139 glioma patients [ 37 ▪ ]. The duotherapy combination levetiracetam with valproic acid ( n = 236) showed better efficacy compared to other duotherapy combinations with either levetiracetam or valproic acid ( n = 119), while level of toxicity was similar [ 34 ▪ ].…”