Levetiracetam Offers Excellent Seizure Control in Brain Tumor Patients

Caroline Cassels

December 04, 2007

December 4, 2007 (Philadelphia, PA) — The antiepileptic drug (AED) levetiracetam ( Keppra, UCB) safely and effectively reduces seizures in patients with primary and metastatic brain tumors, without the risk for adverse drug interactions that could diminish the efficacy of chemotherapy or other antiseizure treatment.

Presented here at the American Epilepsy Society 61st Annual Meeting, a large retrospective study showed complete seizure freedom in 80% of brain tumor patients taking levetiracetam.

According to study investigator Jennifer Connelly, MD, from the Medical College of Wisconsin, in Milwaukee, seizures in brain tumor patients are common and frequently require treatment with AEDs.

The problem is chemotherapeutic agents, and the majority of AEDs are metabolized by the hepatic cytochrome P450 (CYP450) system, which can result in adverse drug interactions, she said.

"This can either cause increased metabolism of the chemotherapeutic agents, which reduces efficacy of the cancer treatment, or reduced efficacy of the AED, which results in increased seizure frequency," Dr. Connelly told Medscape Neurology & Neurosurgery.

However, she added, levetiracetam is not metabolized by the liver and therefore may offer a treatment advantage over other AEDs in this patient population.

She pointed out that several smaller retrospective studies have shown the drug may offer a greater-than-50% reduction in seizures in up to 100% of brain tumor patients — findings that provided the basis for the current study, which is one of the largest to date.

Investigators reviewed the charts of patients who had been referred for brain tumor management to a hospital-based neuro-oncology service from January 2000 to December 2006.

Seizure Control Unaffected by Tumor Subtype

Study participants were older than 18 years, had a diagnosis of primary or metastatic brain tumor and a documented history of seizures, and were receiving levetiracetam alone or in combination with other AEDs.

Patients were excluded if they had been taking levetiracetam for less than 6 months, had a history of noncompliance or pseudoseizures, or had incomplete documentation of seizure history.

The investigators documented seizure control according to change in seizure frequency from baseline as 0%, <25%, 26% – 50%, 51% – 75%, 76% – 99%, and 100% seizure freedom.

With an average of 24 months of follow-up, 80% of the patients had 100% seizure freedom, and of the patients who had no further seizures, 80% were on levetiracetam monotherapy and taking an average dose of 2150 mg per day.

Furthermore, said Dr. Connelly, there was no statistical difference in seizure freedom rate among the various tumor subtypes.

"In general, individuals with low-grade tumors tend to be more epileptogenic. However, tumor subtype made no difference to seizure control, so whether patients had a low-grade or high-grade tumor, seizure control was the same," she said.

Of the total study group, 29 (16%) discontinued levetiracetam therapy. Reasons for discontinuation the drug were similar to those seen in the general epilepsy population, with the most common reason being impact on mood.

The bottom line, said Dr. Connelly, is that levetiracetam is well tolerated and offers excellent seizure control in the majority of brain tumor patients and is less likely to interfere with the efficacy of cancer treatment.

American Epilepsy Society 61st Annual Meeting: Abstract 3.239. Presented December 4, 2007.


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