Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma

Abstract

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.

Effect of anti-epileptic drugs on the survival of patients with glioblastoma multiforme: A retrospective, single-center study

“…If one AED is not enough to control symptoms, it is more effective to add another AED rather than replacing it with another AED [26]. About 60% of patients with GBM in our cohort consequently received more than two AEDs, of which LEV was preferred as a primary or secondary medication because of its relatively low side effects and wide therapeutic range [24,26].…”

“…LEV, a relatively new AED, exhibits not only excellent anti-seizure effects but also fewer side effects [24]. A recent study reported that the mechanism underlying the effects of LEV involves the inhibition of MGMT gene expression via formation of a complex with p53; moreover, it acts as a sensitizer for TMZ [11].…”

Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy

“…Despite there being no specific guidelines for the anticonvulsant choice regarding brain tumor-associated seizures, there is ongoing interest in identifying compounds with anti-tumoral in vitro effects such as levetiracetam (LEV) [ 149 ]; see [ 148 ]. Among more contemporary anticonvulsants, most patients receive LEV for glioma-associated epileptic seizures, and some recent studies have observed a benefit in overall survival [ 150 , 151 , 152 ]. Although the mechanism of this survival benefit has not been directly addressed, it may partly be due to a reduced glutamate-to-GABA ratio [ 153 , 154 ].…”

Clinical Diagnosis and Perioperative Management of Glioma-Related Epilepsy

“…Recent studies on GRE treatment using LEV have suggested good efficacy and favorable safety profile ( 27 , 28 ). With the advantages of improving the cognitive functioning and enhancing the chemotherapeutic efficacy of Temozolomide (TMZ), LEV is widely used for treating GRE as either monotherapy or add-on therapy ( 28 , 29 ). VPA is a broad spectrum, well-tolerated AED that is widely used in epilepsy with brain tumors.…”

“…Brivaracetam is also a promising antiepileptic drug in this group of patients ( 38 ). We summarized the main characteristics of the antiepileptic drugs mentioned above in Table 1 ( 21 , 24 , 28 , 39 ).…”