BACKGROUND: To examine the efficacy of valproic acid (VPA) given either with or 
without levetiracetam (LEV) on seizure control and on survival in patients with 
glioblastoma multiforme (GBM) treated with chemoradiation.
METHODS: A retrospective analysis was performed on 291 patients with GBM. The 
efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) 
patients with seizures with a minimum follow-up of 6 months. Cox-regression 
survival analysis was performed on 165 patients receiving chemoradiation with 
temozolomide of whom 108 receiving this in combination with VPA for at least 3 
months.
RESULTS: Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) 
and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom 
from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and 
in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, 
seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on 
LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on 
monotherapy. Patients using VPA in combination with temozolomide showed a longer 
median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared 
with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 
95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and 
O(6)-DNA methylguanine-methyltransferase promoter methylation status.
CONCLUSIONS: Polytherapy with VPA and LEV more strongly contributes to seizure 
control than does either as monotherapy. Use of VPA together with chemoradiation 
with temozolomide results in a 2-months' longer survival of patients with GBM.