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

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.

Antiseizure medication in patients with Glioblastoma- a collaborative cohort study.

PURPOSE: We investigated, whether epileptic seizures (ES) as presenting symptom in adult patients with GBM are associated with better Overall Survival (OS) compared to ES presenting later during the course of GBM, and efficacy and safety of different antiseizure medications (ASMs). METHODS: Retrospective consecutive cohort study of adults with GBM: 50 from Norway and 50 from Italy. We compared the time to changing ASM treatments. OS was investigated with a Cox regression model adjusted for time dependency. RESULTS: Median follow-up was 17 months from GBM diagnosis. ES were the presenting symptom in 49 patients. All patients received ASM treatment. LEV was the first ASM in the majority of patients and the most effective at one year from the first prescription, (p = 0.004). Occurrence of adverse events (AEs) was similar between LEV and other ASMs (p = 0.47). Poorer OS correlated with older age at GBM diagnosis, country and ASM therapy. A negative impact of ASMs on OS was observed for LEV in a univariate and multivariate analysis, and for VPA (only in multivariate analysis), even when adjusted for O6-methylguanine-DNA-methyltransferase (MGMT) methylation status. Patients with ES as the onset symptom of GBM and patients who had first ES later had similar OS (p = 0.87). CONCLUSION: ES as the GBM debut symptom did not lead to a longer OS. LEV was a more effective ASM compared to other treatments with no differences regarding AEs between LEV and other ASMs. Surprisingly, in our patients LEV and VPA were associated with worse OS than other ASMs. This result should be interpreted with caution due to the retrospective nature of this study along with the many variables which may affect the outcome in this population.

Status epilepticus secondary to glioma.

PURPOSE: Epilepsy is common in glioma patients, but clinical data on the course of status epilepticus (SE) in this group are sparse. The aim of this study was to investigate the relationship of SE to tumor grading, seizure semiology, trigger factors, treatment response, recurrence and outcome of SE in patients with glioma. METHODS: Adult patients with SE and glioma WHO grade II-IV were identified from a prospective clinical study at two neurological departments. We identified 31 SE in 20 patients during a period of 7 years. RESULTS: SE was more frequent in patients with high-grade glioma. Half of the seizures were secondary generalized. Patients with a clinical and radiological stable glioma had SE as often as patients with untreated tumor or tumor in progression. The majority of patients had a well-controlled epilepsy prior to SE. SE responded well to first and second line treatment. Patients with SE and tumor progression were not more refractory to treatment than patients without progression. CONCLUSION: SE secondary to glioma responded well to treatment and should be treated aggressively regardless of the oncological prognosis. Seizures during tumor progression were not more treatment refractory than SE in patients with stable glioma disease.