Efficacy and tolerability of lacosamide in patients with glioma: a prospective study

BACKGROUND: Lacosamide (LCM) has been suggested in some retrospective studies to improve seizure control as an add-on treatment in brain tumor patients. We present here the preliminary results of a prospective study focused on a cohort of patients with gliomas and active epilepsy who received LCM. METHODS: Eligibility criteria were as follows: 1) biopsy-proven grade II or III or IV gliomas according to WHO 2007; 2) persisting seizures (seizure frequency > 1 per month) despite a treatment with 1 or more antiepileptic drugs (AEDs) for at least 3 months and adequate serum concentration; 3) stable steroid dose; 4) available information on tumor response on MRI according to RANO criteria following chemotherapy or radiotherapy; 5) age > 18 years. LCM was given at 50 mg daily for one week with an increase of 50 mg twice daily every week to a target dose of 200-400 mg/day. The endpoints were > 50% decrease of seizure frequency and seizure freedom at 3 and 6 months. RESULTS: Since January 2012 42 patients were enrolled. There were 17 grade II gliomas (5 astrocytomas, 8 oligodendrogliomas, 4 oligoastrocytomas), 13 grade III (4 astrocytomas, 3 oligodendrogliomas, 6 gliomatosis cerebri) and 12 glioblastomas. Ten patients (23.8%) had generalized seizures and 32 (76.2%) partial seizures. Thirty-six patients (85.7%) were on AED monotherapy while 6 (14.3%) on polytherapy. Reasons for introduction of LCM were unacceptable side effects of traditional AEDs in 5 patients (12%) and/or lack of efficacy of previous AEDs associated with either PD in 16 (38%) or without PD in 26 (62%). Median duration of follow up was 6.6 months (range 3-24 months). Among low grade gliomas after 3 months of LCM 5/17 patients (29.4%) had a reduction of >50% of seizure frequency while seizure freedom was obtained in other 3/17 (17.6%); at 6 months a reduction of >50% of seizure frequency was observed in 5 (29.4%) while seizure freedom was obtained in other 2 (11.8%) for overall seizure control of 41.2%. As for high grade gliomas after 3 months 6/25 patients (24%) had a reduction of >50% of seizure frequency while seizure freedom was obtained in other 11/25 (44%); at 6 months a reduction of >50% of seizure frequency was observed in 7/22 (31.8%) and seizure freedom in other 6 (27.3%) for overall seizure control of 59.1% . A resolution of an epileptic status was obtained in 3 patients of whom one receveing LCM alone. Secondary generalized seizures disappeared in 4 patients. However, responding patients were not able to reduce the doses of previous AEDs. Most patients (97.6%) did not report significant toxicities: in 2 cases only LCM was withdrawn due to dizziness and fatigue and resistant epilepsy, respectively. CONCLUSION: Among patients both with high grade and low grade gliomas LCM is well tolerated without interactions with antitumoral treatments. LCM shows significant activity as add-on therapy regardless of tumor response to antineoplastic treatment.