Levetiracetam use during chemoradiation may improve survival in glioblastoma
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Patients with isocitrate dehydrogenase wild-type glioblastoma who used levetiracetam for the duration of chemoradiation may have a higher overall survival rate, according to an observational, retrospective cohort study in Neurology.
“In patients with [isocitrate dehydrogenase (IDH)] wild-type glioblastoma, epileptic seizures are common during the course of the tumor, with incidence ranging up to 30% to 60%, and require long-term use of antiepileptic drugs,” Johan Pallud, MD, PhD, of GHU Paris—Sainte-Anne Hospital, Université de Paris—Sorbonne Paris Cité and Institut de Psychiatrie et Neurosciences de Paris, and colleagues wrote. “Therefore, antiepileptic drugs are often combined with Temozolomide during the standard combined chemoradiation protocol.”
Previous studies have shown a correlation between the antiepileptic drug levetiracetam and glioblastoma survival, so Pallud and colleagues assessed outcomes in 460 adults (270 men; mean age, 60.1 years) newly diagnosed with IDH wild-type supratentorial glioblastoma between December 2010 and December 2018. Patients who used levetiracetam for the duration of standard chemoradiation were case matched 1:1 to those who used it part or none of the time on chemoradiation.
At glioblastoma diagnosis, 162 patients (35.2%) had epileptic seizures, whereas 171 patients (37.2%) were taking at least one antiepileptic medication. There were 116 patients (25.2%) who took levetiracetam for the duration of chemoradiation, 145 (31.5%) who took it part of the time and 199 (43.3%) who never took it.
Factoring in 365 (79.3%) deaths during follow-up, the median overall survival for the whole cohort was 17.4 months (95% CI, 16.3-19). Among those on levetiracetam for the entirety of chemoradiation, median overall survival was 21 months (95% CI, 17.2-24); with part-time and no use of levetiracetam, it was 16.8 months (95% CI, 12.4-19) and 16 months (95% CI, 15.5-19.4), respectively.
Using levetiracetam for the entirety or part of chemoradiation was an independent factor in longer overall survival, and daily dosage did not significantly affect survival. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, partial tumor resection and gross total tumor resection were also independent factors in longer overall survival, the researchers wrote.
“The main take-home message is that — because both epileptogenic and oncogenic processes are intermixed in the specific condition of cerebral diffuse gliomas — an antiepileptic drug can also have anti-tumor effects beyond its effectiveness against epileptic seizures,” Pallud told Healio Neurology. “This has practical implications since one may introduce and/or continue the antiepileptic drug levetiracetam as an anti-tumor adjunct in combination with temozolomide during the standard chemoradiation protocol of IDH wild-type glioblastoma patients.”
Limitations included study design, clinical diagnosis of epileptic seizures, missing data for MGMT promoter methylation and absence of specifics on levetiracetam use.
“At a time where several antiepileptic drugs, such as sodium valproate, perampanel, and levetiracetam, have been suggested to affect IDH wild-type glioblastoma prognosis, further prospective multicentric controlled trials aiming at investigating the survival benefit of each of these drugs compared to an antiepileptic drug devoid of such anti-tumor properties and to the absence of antiepileptic drug should be considered,” the researchers wrote.