Efficacy of anti-epileptic drugs in patients with gliomas and seizures

Abstract

Although seizures in brain tumor patients are common, the knowledge on optimal anti-seizure therapy in this patient group is limited. An observational study was carried out using a database of all patients from the neuro-oncology service during the period 2000-2005, with data on seizure characteristics, therapy with AEDs, the underlying brain tumor and its treatment. A total of 140 brain tumor patients were studied of whom 23.6% had a low-grade glioma, 53.6% a high-grade glioma, and 22.8% belonged to a mixed group existing of ependymoma, meningioma, and brain metastasis. Epilepsy as the presenting sign was more frequent in low-grade vs. high-grade gliomas (69.7 vs. 52%, P = 0.087), and a total of 75.8% of patients developed seizures with low-grade and of 80.0% with high-grade gliomas. Of all 99 patients with seizures, 80.1% received valproic acid (VPA) as first choice, and either levetiracetam (LEV), carbamazepine (CBZ) or lamotrigine (LMT) as the most frequent next choice. Patients treated with a combination of VPA and LEV showed the highest percentage of responders (81.5%), with a decline in seizure frequency of more than two categories in 55.6% and seizure freedom in 59%. No correlation was found between the use of VPA and survival. A combination of VPA and LEV seems effective, if seizure control cannot be achieved by VPA alone. This indicates that adding levetiracetam may be preferable over sequential trials of AED monotherapy in treatment-resistant seizures in patients with brain tumors.

Valproic Acid Inhibits Angiogenesis In Vitro and Glioma Angiogenesis In Vivo in the Brain

“…One researcher reported that there was no remarkable difference in survival between the patients with and without VPA. 25) However, this study was not a randomized control study and has the problem that the ratio of high-grade glioma was not similar between the two groups. Another report demonstrated that VPA was well tolerated in heavily pretreated pediatric patients with high-grade glioma with moderate tumor efficacy.…”

Pharmacists Perspective on Management of GBM

“…The correlating median survival times were 17.3 months, 14.4 months, and 14.0 months, respectively. It has been hypothesized that valproic acid enhances antitumor effects of chemoradiation through inhibition of histone deacetylase, inducing autophagy [42,43].…”

“…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].…”

Zonisamide: Antiproliferative and Antioxidant Effects on C6 Glioma Cancer Cell Model

“…Similar results were obtained from the use of valproic acid. It was reported by Van Bremen et al, that 79.3% in 99 glioma patients with secondary epilepsy remained entirely seizure free after treatment with valproic acid [5]. Zonisamide, due to its antioxidant and with a low level of anti-cancer drugs interaction properties, is also associated with tumor-associated seizures [6,7].…”