Abstracts

Rationale: High-grade glioma is the most common primary malignant brain tumor in adults, and epilepsy is a common secondary problem in these patients. Enzyme-inducing AEDs (EIAED) are known to alter the pharmacokinetics of many chemotherapies resulting in decreased drug levels and potential efficacy. The purpose of this study is to compare the effects on seizure control, response to chemotherapy and survival in high-grade glioma patients treated with EIAED vs. leviteracitam (LEV) vs. other non-EIAED (nEIAED). Methods: Vanderbilt University Medical Center (VUMC) patients over 18 years of age with a malignant glioma and secondary seizure disorder diagnosed between 1/1/2000 and 12/31/2006 were identified through the VUMC Cancer Registry and Neuro-Oncology clinic records. Variables collected included demographic information, seizure type/frequency, tumor pathology/treatment/response and patient survival. Patients were then divided into three groups based on AED regimen (EIAED, LEV or other nEIAED). The data was statistically analyzed using SPSS 16, specifically looking at outcomes and survival. Results: A total of 202 patients were identified and classified as being on an EIAED, LEV or other nEIAED. Of these 202 patients, 90.6% were initially on an EIAED, 4.0% were on LEV and 5.4% were on other nEIAED. Seizure was the presenting symptom in 51.0% of patients followed by headache (27.2%) and focal deficits (14.4%). Seizure type was classified as GTC (33.7%), SPS (27.2%), CPS (12.4%) and unclassified (22.3%). Tumor type consisted of astrocytoma (73.8%), oligodendroglioma/oligoastrocytoma (14.8%) and other cell types (11.4%). 59.9% were WHO grade IV and 41.4% were WHO grade III. 85 patients remained on their initial AED regimen. Of the 202 patients, 117 patients’ AED regimen was changed with 52.1% remaining on an EIAED, 37.6% to LEV and 10.3% to another nEIAED. Of these 117 patients, there were no statistically significant differences in age, seizure type, presenting symptom, tumor cell type or grade between the three AED categories. Using a Kaplan-Meier curve, median survival was 23 months in the EIAED group vs. 22 months in the LEV group and 13 months in the other nEIAED group (p>0.05, log rank). Response to chemotherapy was categorized into one of two groups, radiographic progression vs. stable or responsive disease. Of 102 patients with response data, the percentage of stable/responders was 53.8% in LEV, 47.2% in EIAED and 30.0% in other nEIAED (p>0.05, chi-square). Complete seizure control was obtained in 72.7% in the LEV group, 50.0% in the nEIAED group and 41.0% in the EIAED group (p<0.005, Kruskal Wallis test). Conclusions: More than half of malignant glioma patients were switched from their original AED regimen in favor of reducing the number of patients on an EIAED. Though not statistically significant, there was a trend of improved survival and response to chemotherapy in patients on LEV vs. other nEIAED. Complete seizure control was significantly greater in LEV vs. both EIAED and other nEIAED (p<0.005).