Optimizing therapy of seizures in patients with brain tumors

Abstract

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with structural brain lesions, and a role for multidrug-resistance proteins has been suggested. The medical treatment of epilepsy in brain tumor patients has mainly been studied retrospectively, and the optimal management of seizures with antiepileptic drugs (AEDs) is unclear. Enzyme-inducing anticonvulsants are generally not recommended because they can lead to insufficient serum levels of concomitantly administered chemotherapeutic drugs. Although valproic acid is an enzyme inhibitor and may therefore lead to toxic levels of simultaneously administered chemotherapeutic agents, this does not appear to be a major problem in patients with brain tumors. Preliminary observations of add-on treatment with the AEDs levetiracetam or gabapentin suggest that these non-enzyme-inducing AEDs can be useful for control of seizures in patients with brain tumors. Conversely, prophylactic use of AEDs in brain tumor patients is generally not recommended.

Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial

“…Several new AED are available that are devoid of clinically relevant drug interactions and do not influence hepatic metabolism. Therefore, although newer AED do not demonstrate a better efficacy, they are preferable for the treatment of brain tumor-related epilepsies (7,(24)(25)(26). One major disadvantage of most newer AED, however, is the lack of an intravenous formulation, that is necessary in emergency situations or in the perioperative phase.…”

Pharmacists Perspective on Management of GBM

“…Van Breemen and colleagues found valproic acid alone and in combination with levetiracetam resulted in a 79.3% and 81.5% seizure response rate, respectively [43]. Considerations for use of valproic acid include thrombocytopenia, drug interactions due to inhibition of CYP2C9, the need for add-on agents for further seizure control in some patients, and therapeutic drug monitoring [40,44]. Levetiracetam may also be effective monotherapy, with the benefits of good tolerance, lack of drug interactions and no need for therapeutic drug monitoring [40].…”

“…Phenytoin is another AED commonly used as monotherapy due to its efficacy, but has disadvantages of drug interactions, required therapeutic drug monitoring, and dose-related adverse effects, including drowsiness and dizziness [40,44]. The drug interaction between phenytoin and dexamethasone is especially concerning.…”

“…Therapeutic doses of phenytoin when used concomitantly with dexamethasone have been reported as high as 600 to 1000 mg/day. Other AEDs used as monotherapy in patients with GBM include topiramate, zonisamide, and lamotrigine [40,44].…”

Manejo perioperatorio de tumores intracraneales: rol del neurocirujano

“…Cerca de un 3050% de los pacientes con tumores cerebrales debutan con convulsiones como síntoma inicial 80,81 . El riesgo de convulsionar varía de acuerdo al tipo de tumor, su grado y ubicación 82,83 . Diversos estudios retrospectivos no han podido demostrar beneficios de la profi laxis anticonvulsivante 8487 y, peor aún, se conoce que los anticonvulsivantes tienen interacciones con los corticoides y los quimioterápicos 82,88 .…”