Objective:

We explore the impact of levetiracetam dose on both cancer survival and seizure outcomes to assess whether patients with high-grade glioma (HGG)-associated epilepsy may benefit from future disease-specific dosing guidelines.

Background:

Levetiracetam is a widely-preferred first line therapy for tumor-associated epilepsy. Preclinical studies propose that levetiracetam sensitizes malignant glioma cells to the methylating agent temozolomide. However, clinical studies have shown mixed results between levetiracetam and HGG outcomes, and there is minimal data on optimal levetiracetam dosing in tumor-associated epilepsy. A more thorough understanding of the relationship between levetiracetam and clinical outcomes may help guide prescribing.

Design/Methods:

We identified 422 patients with co-occurring HGG and epileptic activity. Multivariable linear regressions were applied to the full patient sample as well as patients who did and did not receive standard-of-care (SOC) chemoradiation with temozolomide (SOC+/-). Levetiracetam dose was analyzed both as a numeric variable and as a Low (<2000mg/day) versus High (≥2000mg/day) categorical variable. Age, sex, targeted anticancer therapies, gross total resection, and MGMT methylation status were included as additional variables. Outcomes included progression-free and overall survival (PFS and OS), achievement of a six-month seizure remission, and duration of seizure remission.

Results:

In the full patient sample, initial treatment with levetiracetam associated with significantly increased likelihood of achieving seizure remission (p = 0.0019), but not with improved PFS or OS. The SOC+ group likewise demonstrated a significant association (p = 0.00163) between levetiracetam and seizure remission, a finding not seen in the SOC- group. In all analyzed groups, levetiracetam dose did not associate with any outcomes of interest.

Conclusions: