Anti-epileptic Therapy with Lamotrigine Associated with Improved Progression-free Survival in High-grade Glioma: A Large-series Analysis
Ryan Rilinger1, Akshay Sharma2, Lydia Guo1, Matthew Grabowski2, Mina Lobbous3
1Cleveland Clinic Lerner College of Medicine, 2Department of Neurosurgery, 3Department of Neuro-Oncology, Cleveland Clinic Foundation
Objective:
We characterize the prognostic impact of the most common anti-epileptic drugs (AEDs) employed in high-grade gliomas (HGG) over the past twenty years. This information seeks to expand the understanding of potential mechanisms behind the demonstrated association between epileptic activity and improved prognosis in HGG.
Background:
High-grade gliomas (HGG) are aggressive brain tumors with notoriously poor prognoses and high symptomatic burden, including seizures in 30-60% of HGG cases. Prior research demonstrates associations between positive seizure history at initial HGG presentation and better overall survival. Additional findings from our lab suggest a positive prognostic value for post-diagnosis epileptic presentation. However, other recent literature findings suggest epileptic activity associates with glioma progression. Seeking to explore mechanisms behind the prognostic benefit of epileptic activity, we hypothesized a role of AEDs in HGG prognosis and sought to identify the impact of different AEDs.
Design/Methods:
We identified 950 patients with HGG from a twenty-year database, 422 of whom also had epileptic activity (44%). Multivariable linear regression was used to assess the impact of the five most commonly prescribed AEDs among our patient sample (levetiracetam, phenytoin, lacosamide, lamotrigine, and zonisamide). Additional variables in the regression included age, treatment exposure (radiation therapy, cytotoxic chemotherapy, or targeted chemotherapy), and extent of surgical resection (gross total resection versus all other surgeries).
Results:
We identified a statistically significant (p = 0.015) association between use of lamotrigine as an AED and increased progression-free survival, though there was no significant effect on overall survival. The other four AEDs studied did not associate with progression-free survival (levetiracetam: p = 0.926, phenytoin: p = 0.316, lacosamide: p = 0.396, zonisamide: p = 0.557) or overall survival.
Conclusions:
The prolongation of progression-free survival in patients with HGG-associated epilepsy on lamotrigine therapy suggests a potential connection between AED use and HGG disease course.