Correlation between SV2A expression in tumour tissue and efficacy of levetiracetam in glioma patients with epilepsy
01 / 2011 - unknown
Levetiracetam is a relatively novel anti-epileptic drug (AED), which has proven to be effective and well tolerated in many glioma patients with otherwise pharmacoresistant epilepsy. Moreover, levetiracetam has neither enzyme-inducing nor enzyme-inhibiting properties, which makes the drug particularly attractive for brain tumor patients, as they frequently receive chemotherapy and/or corticosteroids. Therefore, levetiracetam is the anti-epileptic drug of choice post-operatively in glioma patients suffering from epilepsy. Unfortunately, even with levetiracetam, a proportion of glioma patients is not free of seizures. It is unclear, however, which glioma patients benefit from levetiracetam treatment. Better selection of glioma patients with seizures for treatment with levetiracetam would avoid unnecessary and ineffective treatment with levetiracetam. Recently the synaptic vesicle protein 2A (SV2A) has been demonstrated to be the binding site for levetiracetam. It is suggested that the expression of SV2A is correlated with clinical response to levetiracetam. The determination of SV2A expression in brain (tumor) tissue might be used as a predictive tool for response to levetiracetam. The objective of this project is to correlate SV2A expression in surgically removed tumor and tumor-surrounding tissue of glioma patients suffering from epilepsy with their clinical response to levetiracetam. For that purpose, we will include 40 post-operative adult (> 18 years) glioma patients, pre-operatively suffering from partial seizures, whether or not with secondary generalisation, who are treated with levetiracetam. We will determine the total number of seizures and time to drug withdrawal due to inadequate seizure control (if applicable) during the study period, which is 6 months for every patient. We will also determine neurocognitive performance, electrical brain activity, and impact on health-related quality of life at baseline and at the end of the study period. We will determine blood levels of levetiracetam at the start and at the end of the study period. We will determine expression of SV2A by means of immuno-histochemistry and reverse transcriptase polymerase chain reaction on tumor (-surrounding) tissue. We will correlate the clinical outcome with SV2A expression.