The withdrawal of antiepileptic drugs in patients with low-grade and anaplastic glioma

Abstract

The withdrawal of antiepileptic drugs (AEDs) in World Health Organization (WHO) grade II-III glioma patients with epilepsy is controversial, as the presence of a symptomatic lesion is often related to an increased risk of seizure relapse. However, some glioma patients may achieve long-term seizure freedom after antitumor treatment, raising questions about the necessity to continue AEDs, particularly when patients experience serious drug side effects. Areas covered: In this review, we show the evidence in the literature from 1990-2016 for AED withdrawal in glioma patients. We put this issue into the context of risk factors for developing seizures in glioma, adverse effects of AEDs, seizure outcome after antitumor treatment, and outcome after AED withdrawal in patients with non-brain tumor related epilepsy. Expert commentary: There is currently scarce evidence of the feasibility of AED withdrawal in glioma patients. AED withdrawal could be considered in patients with grade II-III glioma with a favorable prognosis, who have achieved stable disease and long-term seizure freedom. The potential benefits of AED withdrawal need to be carefully weighed against the presumed risk of seizure recurrence in a shared decision-making process by both the clinical physician and the patient.

Withdrawal of antiepileptic drugs in patients with low grade and anaplastic glioma after long-term seizure freedom: a prospective observational study

“…The risk of seizure relapse after AED withdrawal in glioma patients appears to be comparable with the general epilepsy population with non-brain tumor related epilepsy [ 23 – 25 ]. In the general epilepsy population, followed for variable periods of time ranging from 3 months to 23 years, a recurrence rate of 12–66% was reported [ 5 , 25 , 26 ]. Predictors for seizure recurrence after withdrawal in the general epilepsy population include AED polytherapy, longer duration of active epilepsy, having experienced seizures after the start of AED treatment, and having an abnormal EEG [ 26 ].…”

“…In clinical practice, there is no doubt that glioma patients who develop seizures require treatment with AEDs. To achieve adequate seizure control, levetiracetam and valproic acid are the mostly supported treatment options [ 5 ], but alternative AEDs as lamotrigine, lacosamide, topiramate, zonisamide or pregabaline also have shown a favorable efficacy and toxicity profile and limited interactions with other drugs such as chemotherapeutic agents [ 6 – 9 ]. Still, in 20–40% of glioma patients AED side-effects occur, such as somnolence, dizziness, fatigue, cognitive disturbances, and mood or behavioral changes [ 5 , 10 ].…”

“…To achieve adequate seizure control, levetiracetam and valproic acid are the mostly supported treatment options [ 5 ], but alternative AEDs as lamotrigine, lacosamide, topiramate, zonisamide or pregabaline also have shown a favorable efficacy and toxicity profile and limited interactions with other drugs such as chemotherapeutic agents [ 6 – 9 ]. Still, in 20–40% of glioma patients AED side-effects occur, such as somnolence, dizziness, fatigue, cognitive disturbances, and mood or behavioral changes [ 5 , 10 ]. Besides seizures, the tumor itself and antitumor treatments, the cumulative effects of AED treatment are also likely to contribute to cognitive dysfunction, behavioral changes and a decrease in quality of life [ 10 – 13 ].…”

“…In the light of potential side effects and costs of long-term AED use and the efficacy of anti-tumor treatment regarding seizures, the question arises whether withdrawal of AEDs after an interval of seizure freedom should be considered [ 5 ]. Based on retrospective studies, a seizure recurrence rate after withdrawal between 12.5 and 27% has been reported in patients with mostly intra-axial brain tumors [ 5 ]. Currently, it is unknown if glioma patients and their physicians are willing to withdraw AEDs after long-term seizure freedom, and more importantly, no prospective studies exist on the risk of seizure recurrence in glioma patients after AED withdrawal.…”

Clinical practice guidelines for the diagnosis and treatment of adult diffuse glioma‐related epilepsy

“…For patients with preoperative GRE, patients can withdraw AEDs after a minimum of 1 year of seizure freedom when their seizure histories are shorter than 6 months and tumors are completely removed, however, for those with a long seizure history, incomplete tumor resection, distant epileptiform EEG discharges, preoperative drug‐resistant seizures or focal seizures without a loss of consciousness, we recommend that the optimal timing of AED withdrawal should be at least 2 years without seizures after the surgery and needs to be considered carefully . AED withdrawal is not recommended for two subgroups in any case: (a) all GBM patients; (b) other HGG patients (patients with anaplastic glioma) with incomplete tumor resection or intractable postoperative seizures.…”