Abstracts

Rationale: Levetiracetam (LEV) is an FDA approved anti-epileptic drug for adjunctive therapy of partial seizures and primary generalized epilepsy. Several small retrospective studies of LEV demonstrated efficacy for seizure management in patients with brain tumors. We proposed that LEV provided significant seizure freedom among patients with brain tumors in a large retrospective study.Methods: This was an IRB-approved retrospective chart review of patients referred to the Neuro-oncology Service at an academic medical center for management of brain tumors from January 2000 to December 2006. Inclusion criteria were: 1) diagnosis of a primary or metastatic brain tumor, 2) documented history of seizures, 3) age greater than 18 years, and 4) patients receiving LEV treatment as either monotherapy or polytherapy. Exclusion criteria were: 1) documented history of non-compliance, 2) history of pseudoseizures, and 3) lack of complete documentation of seizure history. Additional information was obtained on tumor type, date of seizure onset, seizure frequency, dose of LEV, and reasons for discontinuation of LEV therapy. Seizure control was documented according to a change in seizure frequency from baseline as 0%, <25%, 26-50%, 51-75%, 76-99%, and 100% seizure freedom. Note that data collection is ongoing at the time of abstract submission; it is anticipated that ultimately data on 200 patients will be reported.Results: A total of 154 patients out of 214 charts screened met all the inclusion criteria. Patients were excluded due to brain biopsy negative for tumor and for incomplete documentation. 146/154 (95%)patients were diagnosed with primary brain tumors and the remaining 8/154 (5%)had metastatic brain tumors. 124 out of 154 (80.5%) patients had complete seizure freedom on an average daily dose of 2100 mg of LEV. There was no apparent statistically significant difference in rates of seizure control between various tumor types. A total of 91/124 (73%) patients were on LEV monotherapy. Discontinuation rates were higher among patients with seizure freedom than those without seizure freedom, 14.5% vs. 10% respectively.Conclusions: Seizures are a common manifestation in patients with primary brain and metastatic tumors. Several AEDs are metabolized by the hepatic cytochrome P450 system, as are many of the therapeutic interventions for brain tumors such as chemotherapeutic agents and dexamethasone. It is well documented that drug interactions decrease the efficacy of chemotherapeutic agents and AEDs in patients who are taking both. LEV is not hepatically metabolized, thus minimizing the risk. This is the largest retrospective study to date that demonstrates excellent seizure freedom rates using LEV for patients with brain tumors. The majority of patients were on LEV monotherapy, suggesting that in this patient population LEV monotherapy is effective. Interestingly, patients were more likely to discontinue LEV due to adverse events when they were seizure free. Larger prospective studies are needed to validate the efficacy and safety of levetiracetam as monotherapy among patients with brain tumors.