Carbamazepine for Epilepsy Treatment in Glioblastoma Patients: A Review and a Clinical Case

Glioblastoma is a malignant brain tumor characterized by an aggressive course, resistance to chemoradiation and immunotherapy, recurrence, and high mortality. The incidence of glioblastoma ranges from 3.2 to 5 per 100,000 people. In recent years, an increase in the incidence of glioblastoma among patients under 45 years of age has been observed. Epilepsy develops in 25–60% of the patients, reducing their quality of life and worsening the prognosis of the disease. In 35–40% of the patients, epileptic seizures are the first manifestation of glioblastoma, being also possible during its treatment or relapse. The risk of epilepsy development and its severity are affected by the tumor volume, growth pattern, localization, presence of preoperative seizures, IDH1-2 mutations, and residual tumor volume. The epilepsy associated with glioblastoma is characterized by a multifactorial and poorly understood etiopathogenesis. The leading role in epileptogenesis is attributed to dysfunction of ion channels with an increase in the level of extracellular K⁺, hyperexpression of SCN1A and SCN2A alpha subunits of Na⁺ channels, as well as dysregulatory Ca²⁺ channels. As a result, in the peritumoral zone, the homeostasis of inhibitory and excitatory neurotransmitters, repolarization/depolarization processes, and electrochemical interactions between neurons and tumor cells are disrupted. Due to its high clinical effectiveness, carbamazepine is most often used to treat glioblastoma-associated epilepsy. The antiepileptic activity of carbamazepine is related to the inactivation of Na⁺ channels, potentiation of potential-dependent K⁺, Cl^– channels, the GABA-ergic system, inhibition of glutamate release, and the effect on the homeostasis of other neurotransmitter systems in the brain. The ability of carbamazepine to suppress cell proliferation in a number of malignant glioma cell lines is also of high significance. Although carbamazepine is an inducer of liver microsomal enzymes, it does not reduce the effectiveness of temozolomide, which is not metabolized in the liver. Possible adverse carbamazepine-associated reactions do not require its discontinuation. Given the high clinical effectiveness of carbamazepine, further studies of its pleiotropic effects in patients with epilepsy associated with glioblastoma and other malignant brain tumors are required.

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