Antiepileptogenic Trials in Patients With Brain Tumour
Up to 60% of people with brain tumours may present with seizures or have seizures for the first time after diagnosis or neurosurgery. This high risk of seizures (depending on tumour type, grade, and location) makes primary prevention with AEDs an option worth considering. However, the use of ASDs in primary prevention of seizure is complicated by the risk of adverse effects (some of them occurring more frequently in patients with brain tumours than in other patient groups) and interactions with steroids and chemotherapy (resulting in inadequate chemotherapeutic dosing), which limit the use of ASDs, especially those with enzyme-inducing effect.
A Cochrane review (including five RCTs, 404 participants) found no difference between AEDs (phenobarbital, phenytoin, valproate) and placebo/no treatment in preventing a first seizure in patients with brain tumours. Conversely, the risk of an adverse event was much higher for patients receiving ASDs (number needed to harm 3; RR 6.10, 95% CI 1.10–34.63; P = 0.046). Adverse effects reported were nausea, skin rash, sore gums, myelosuppression, vertigo, blurred vision, tremor, and gait unsteadiness. No study evaluating newer AEDs was identified.
The evidence for seizure prophylaxis with older ASDs in patients with brain tumours is therefore inconclusive, and limited by the higher risk of adverse effects, which may lessen their overall benefit ( Table 2 ).
However, very recent data might support the use of valproate in patients undergoing chemotherapy (with temozolomide) and/or radiotherapy for malignant glioblastoma. Several studies have shown that valproate is associated with improved survival and better seizure control in these patients, probably by increasing temozolomide bioavailability or by acting as an inhibitor of histone deacetylases with subsequent increased sensibilization for radiochemotherapy in vivo. However, one study failed to find a significant influence on overall patient survival. Hence, although valproate seems to represent a promising disease-modifying therapy for brain tumours, that might also prevent associated epileptogenesis, further studies are warranted to conclude on its influence on tumour progression and related seizure outcomes.