Effect of anti-epileptic drugs on the survival of patients with glioblastoma multiforme: A retrospective, single-center study

• Published in: PloS one Vol. 14; no. 12; p. e0225599
• Main Authors: Ryu, Jae Yeoul, Min, Kyoung Lok, Chang, Min Jung
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.12.2019; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Analysis; Anticancer properties; Anticonvulsants; Anticonvulsants - administration & dosage; Antiepileptic agents; Antineoplastic Agents, Alkylating - therapeutic use; Antitumor activity; Astrocytoma; Biology and Life Sciences; Brain cancer; Brain Neoplasms - complications; Brain Neoplasms - mortality; Brain Neoplasms - therapy; Cancer; Central nervous system; Chemoradiotherapy - methods; Chemotherapy; Child; Child, Preschool; Confidence intervals; Deoxyribonucleic acid; DNA; DNA methyltransferase; Dose Fractionation, Radiation; Drug therapy; Drugs; Epilepsy; Etiracetam; Female; Follow-Up Studies; Fosphenytoin; Glioblastoma; Glioblastoma - complications; Glioblastoma - mortality; Glioblastoma - therapy; Glioblastoma multiforme; Glioblastomas; Gliomas; Health; Humans; Kaplan-Meier Estimate; Kinases; Lacosamide; Lamotrigine; Levetiracetam; Levetiracetam - administration & dosage; Male; Medical prognosis; Medical research; Medicine and Health Sciences; Methylguanine; Middle Aged; Mutation; O6-methylguanine-DNA methyltransferase; Operating systems (Software); Oxcarbazepine; Patient outcomes; Patients; Perampanel; Physical Sciences; Public health; Quality of Life; Radiation therapy; Radiotherapy; Republic of Korea - epidemiology; Retrospective Studies; Risk analysis; Risk Factors; Seizures; Seizures (Medicine); Seizures - drug therapy; Seizures - etiology; Statistical analysis; Statistical significance; Surgery; Survival; Temozolomide; Temozolomide - therapeutic use; Time Factors; Transferases; Treatment Outcome; Tumors; Young Adult; Republic of Korea; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0225599

Glioblastoma multiforme (GBM) is a lethal and aggressive malignant tumor of the central nervous system. The World Health Organization classifies it as a grade IV astrocytoma. Controlling seizures is essential during GBM treatment because they are often present and closely associated with the quality of life of GBM patients. Some antiepileptic drugs (AEDs) exhibit antitumor effects and could decrease the mortality of patients with GBM. In this retrospective cohort study, we examined 418 patients treated with surgery, radiotherapy, and chemotherapy with temozolomide (TMZ) at Severance Hospital in South Korea, per the current protocol. Median overall survival (OS) was 21 months [95% confidence interval (CI): 18.1-23.9] in the levetiracetam (LEV) treatment group, whereas it was 16 months [95% CI: 14.1-17.9] in the group without LEV, exhibiting a statistically significant difference between the two groups (P < 0.001). Of nine AED groups, only LEV treatment [P = 0.001; hazard ratio (HR), 0.65; 95% CI: 0.51-0.83] exhibited a statistically significant difference in the OS, in the univariate analysis. In the risk analysis of the baseline characteristics, age, administration of LEV, and O6-methylguanine-DNA methyltransferase (MGMT) promoter status correlated with OS. The use of LEV in the group with a methylated MGMT promoter resulted in a positive impact on the OS [P = 0.006; HR, 0.174; 95% CI: 0.050-0.608], but the effect of LEV on the OS was not statistically significant in the unmethylated MGMT promoter group (P = 0.623). This study suggests that, compared with other AEDs, the administration of LEV may prolong the survival period in GBM patients with methylated MGMT promoters, who are undergoing chemotherapy with TMZ.