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Does the choice of antiepileptic drug affect survival in glioblastoma patients?

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Abstract

Patients with glioblastoma (GBM) often suffer from symptomatic epilepsy. Older antiepileptic drugs (AEDs) which affect the enzyme system cytochrome P450 have been in extensive use, but there is an increasing focus on interactions with other drugs. This study investigated whether newer AEDs with little or no enzyme effect are increasingly preferred. Previous research has indicated that valproate improves survival in GBM. We investigated the impact of AEDs on overall survival in GBM patients. All GBM patients diagnosed in Norway 2004–2010 were included through a linkage of national registries, and follow-up data on the malignancy and drug usage were analyzed. In a multivariate cox proportional-hazards regression, AEDs were adjusted for each other and for relevant factors. Immortal time bias was eliminated with time-dependent variables. The study population was 1263 patients with histologically confirmed GBM. Carbamazepine was the most frequently prescribed AED to patients diagnosed with GBM during 2004–2006, while levetiracetam was increasingly prescribed to patients diagnosed later. Taking AEDs on a reimbursement code of epilepsy was not beneficial for survival. None of the six AEDs valproate, levetiracetam, carbamazepine, oxcarbazepine, lamotrigine or phenytoin significantly altered overall survival. There has been a shift in the prescriptions of AEDs to GBM patients from older to newer AEDs over time. We found no significant survival benefit in GBM patients neither from treatment with AEDs for epilepsy in general, nor from the usage of six separate AEDs.

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Acknowledgments

The study has used data from the Cancer Registry of Norway. The interpretation and reporting of these data are the sole responsibility of the authors, and no endorsement by the Cancer Registry of Norway is intended nor should be inferred. We thank Tom Børge Johannesen (MD, PhD) for facilitating the data collection in this study.

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Department of Clinical Medicine 1, University of Bergen, Norway.

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Authors and Affiliations

  1. Department of Neurology, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway

    Kristin M. Knudsen-Baas, Nils Erik Gilhus, Anette M. Storstein & Jone F. Owe

  2. Department of Clinical Medicine 1, University of Bergen, 5021, Bergen, Norway

    Kristin M. Knudsen-Baas, Nils Erik Gilhus & Anette M. Storstein

  3. Department of Pharmacoepidemiology, Domain of Mental and Physical Health, Norwegian Institute of Public Health, 5020, Bergen, Norway

    Anders Engeland

  4. Department of Global Public Health and Primary Care, University of Bergen, 5020, Bergen, Norway

    Anders Engeland

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  1. Kristin M. Knudsen-Baas
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  2. Anders Engeland
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  5. Jone F. Owe
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Correspondence to Kristin M. Knudsen-Baas.

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The study employs anonymous data in mandatory national registries only and complies with the ethical standards for use of these registries.

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The authors declare no conflict of interest.

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Knudsen-Baas, K.M., Engeland, A., Gilhus, N.E. et al. Does the choice of antiepileptic drug affect survival in glioblastoma patients?. J Neurooncol 129, 461–469 (2016). https://doi.org/10.1007/s11060-016-2191-0

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