Clobazam as an add-on treatment for medically refractory brain tumor-related epilepsy.

Abstract

e14038 Background: Over 25,000 patients receive a new diagnosis of a malignant primary brain tumor yearly and of those patients between 30-70% will experience at least one seizure (Maschio, 2015). Brain tumor related epilepsy (BTRE) can have significant negative impacts on patients’ quality of life and treatment must consider the additional complexities of concurrent oncological care. Even with the recent advances in treatment, 15.0% of glioblastoma BTRE patients and 40.0% of grade 2 glioma patients with BTRE experience medically refractory seizures (Newton, 2024). Clobazam, a 1,5 benzodiazepine, is being explored as a potential add on treatment for BTRE patients with refractory seizures. Methods: This single study retrospective analysis evaluates 48 patients from Northwestern’s Malnati Brain Tumor Institute diagnosed with primary brain tumors and received clobazam at some point in their treatment between June 2017- June 2024. Seizure type and frequency, as well as side effects and other pertinent variables were measured upon initiation of clobazam, after 6 months of clobazam treatment, and at the most recent follow up. A modified Engel score was used to evaluate treatment outcomes. Results: 48 patients met study criteria (21 glioblastoma, 3 diffuse astrocytoma, 11 oligodendroglioma, 8 anaplastic astrocytoma, 5 other). At the 6-month time period, 68.8% of patients (33/48) were seizure free with 89.6% of patients (43/48) having modified Engel Scores of I or II, indicating a significant decrease in seizure frequency. Almost all patients who attained seizure freedom on clobazam (98.0%) attained it within 6 months of starting treatment, and the average dose for seizure freedom was 21.3 mg daily dosing. The number of ASMs in addition to clobazam that patients were on at the initial timepoint, 6 month follow up, and most recent time point were also evaluated. 98% (47/48) of patients did not require additional ASMs by 6 months, and 33.3% (16/48) were able to decrease the number of ASMs they were taking. With clobazam, the most common side effects reported included fatigue, lethargy, and headaches, present in 35.4% (17/48) of patients. Conclusions: This data suggests that clobazam is an effective add on medication for patients with medically refractory tumoral epilepsy. Furthermore, the data strongly suggests that if patients are going to respond to clobazam, a response is typically seen within 6 months, which can help guide clinical decision making for patients starting clobazam. An improvement in seizure burden is a clear goal for patients with BTRE, although the ability to wean concurrent agents is similarly an essential goal of treatment. More research is needed to better predict when weaning concurrent agents can be pursued with minimal risk, whether clobazam should be considered as a first line agent, and furthermore, further characterize which patients respond positively to clobazam, and whether other ASMs can be weaned.