Abstracts

Rationale: Phenytoin (PHT) has long been the mainstay of antiepileptic drug therapy. However the availability of newer, efficacious AEDs with lower potential for drug interactions such as Levetiracetam (LEV) with its cytochrome P450 independent metabolism, ease of administration and availability of an intravenous dosage form offers additional benefits. Herein we compare the tolerability and efficacy of LEV with PHT among patients with primary brain tumors. Methods: All patients (> 19 years, with primary brain tumors) treated with either LEV and/ or PHT, prophylactically or therapeutically were included. Patients receiving both phenytoin and levetiracetam concomitantly were excluded. Information on age, gender, date of diagnosis, tumor type and location, AED use/ dose, seizure frequency, AED efficacy and toxicity was documented. Efficacy was defined as seizure freedom after initiation of PHT or LEV therapy. Efficacy of AED therapy was evaluated using logistic regression after adjustment for race, gender, tumor type, AED dose, current concomitant AED therapy and therapeutic versus prophylactic used of AED. Results: Of the 554 patients under the care of the neuro-oncology practice, 168 (84 PHT, dose 367.1 + 118.7 mg/day; 84 LEV, dose 1883.9+ 876.8 mg/day) patients meeting study criteria were included in this analyses. In multivariable analyses LEV demonstrated a four-fold higher efficacy (OR=3.8, 95%CI=1.0- 14.6; p=0.047) compared to PHT, after adjustment for age, gender, race, AED dose, tumor diagnoses and combination AED therapy. Age, gender, race, AED dose and tumor diagnoses did not influence efficacy (all p-values >0.15). Patients on combination AED therapy were four times more likely to demonstrate efficacy (OR=3.9, 95%CI 1.4-11.0; p=0.009) compared to patients on monotherapy. Recognizing that therapy was initiated prophylactically in 13% of LEV patients and 21% of PHT patients, we re-evaluated the efficacy with therapeutic use (i.e. initiation after a seizure). LEV demonstrated a four-fold higher efficacy compared to PHT, after adjustment for age, gender, race, AED dose, tumor diagnoses and combination AED therapy. However this finding was marginally statistically significant (OR=3.7, 95%CI =0.9-14.1; p=0.052). Age, gender, race, AED dose and tumor diagnoses did not influence efficacy (all p-values >0.15). Patients on combination AED therapy were four times more likely to demonstrate efficacy (OR=4.0, 95%CI=1.4-11.3; p=0.008) compared to patients on monotherapy. Three (3.6%) patients in the PHT group and one (1.2%) patient in the LEV group discontinued therapy due to adverse events. Multivariable analyses of tolerability demonstrated no significant differences between phenytoin and levetiracetam after adjustment for age, gender, AED dose, and combination AED therapy (p=0.48). Conclusions: In this retrospective review, compared to phenytoin, levetiracetam showed comparable tolerability and marginally superior efficacy among patients with primary brain tumors.