Antiepileptic drugs in glioblastoma survival: dichotomic or treatment and mechanism of action-dependent variable?

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Abstract Background Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. Methods We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. Results A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS—median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients ­taking AEDs. Conclusion There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments.

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