Lacosamide in patients with gliomas and uncontrolled seizures: results from an observational study

Abstract

To report the efficacy and tolerability of lacosamide as an add-on treatment in patients with gliomas and uncontrolled seizures despite conventional antiepileptic drugs (AEDs). We conducted an observational study on 71 patients to describe patterns of response to lacosamide and the association between clinico-pathological factors and seizure control. We observed at 3, 6 and 9 months a seizure reduction ≥ 50% in 74.6, 76 and 86.2% of patients and a seizure freedom in 42.2, 43 and 50%, respectively. The median number of seizures in the 3 months before treatment was 13, and decreased to 3 between baseline and 6 months, and to 0.5 between 6 and 9 months. The best seizure response was observed at 3 months (62%). Sixty per cent of patients displayed the maximum seizure control with doses of lacosamide of 100-250 mg/day, while 21% needed doses up to 400 mg/day. Seizure reduction ≥ 50% and seizure freedom were higher in patients who received lacosamide as first add-on compared to those who received a later adjunctive therapy. A reduction ≥ 50% of seizures was observed in a proportion of patients with progressive disease on MRI. Age > 45 years (OR 0.11, 95% CI 0.02-0.63, p = 0.013) was a significant predictor of seizure freedom at 9 months on multivariate analysis. The study suggests that lacosamide, when added to any baseline AEDs, is effective in obtaining a high seizure reduction and seizure freedom regardless of the tumor activity and response to antineoplastic therapies.

Effectiveness and tolerability of lacosamide as add‐on therapy in patients with brain tumor–related epilepsy: Results from a prospective, noninterventional study in European clinical practice (VIBES)

“…Results are consistent with the responder rates observed in three prospective studies that investigated the effectiveness of add‐on lacosamide in heterogeneous groups of patients with high‐ or low‐grade gliomas and uncontrolled focal seizures 14‐15,18 . One of these was an observational study (N = 71) which found a 50% responder rate of 76% with add‐on lacosamide at 6 months; 43% of patients were seizure‐free at 6 months 15 . In that study, levetiracetam was also the most frequent concomitant AED.…”

“…Lacosamide was well tolerated by most patients with BTRE; the most common ADRs were vertigo, headache, nausea, and asthenia, in line with the adverse event profile reported with add‐on lacosamide in adults with focal seizures 30‐33 . Previous studies of lacosamide in patients with brain tumor‐related epilepsy have also shown a favorable tolerability profile 15,16 . One of these studies was a retrospective chart review of data from 70 patients predominantly with glioma, who were treated mainly with add‐on lacosamide, which reported that 77% of patients had no toxicities 16 .…”

“…Lacosamide is a non–enzyme‐inducing AED indicated for the treatment of focal (partial onset) seizures in patients ≥4 years of age in the European Union and the USA 12,13 . Published data from retrospective and prospective studies has shown good tolerability and effectiveness of lacosamide in patients with BTRE 14‐18 . The primary objective of the current study was to evaluate the effectiveness of lacosamide added to one or two AEDs in the treatment of patients with BTRE, based on the 50% responder rate and patients’ global impression of change.…”

Seizures in patients with cancer

“…It has low protein binding, no induction or inhibition of hepatic enzymes, few drug interactions, and low incidence of side effects (however, because it can cause PR interval prolongation, it should not be initiated in patients with PR >200 msec). Lacosamide has tablet, liquid, and intravenous formulations and is generally well tolerated in patients with brain tumors . Lamotrigine, perampanel, zonisamide, and clobazam are other good choices.…”

“…Lacosamide has tablet, liquid, and intravenous formulations and is generally well tolerated in patients with brain tumors. 72,73 Lamotrigine, perampanel, zonisamide, and clobazam are other good choices. Pregabalin and gabapentin may be less efficacious but can be helpful in add-on therapy, are well tolerated, and can be quickly up-titrated.…”