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. 2013 Jul;15(7):961-7.
doi: 10.1093/neuonc/not057. Epub 2013 May 16.

Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme

Melissa Kerkhof  1 , Janneke C M Dielemans, Melanie S van Breemen, Hanneke Zwinkels, Robert Walchenbach, Martin J Taphoorn, Charles J Vecht
Affiliations

Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme

Melissa Kerkhof et al. Neuro Oncol. 2013 Jul.

Abstract

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.

Keywords: epilepsy; glioblastoma multiforme; levetiracetam; survival; valproic acid.

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Figures

Fig. 1.
Fig. 1.
Status of the initial cohort of patients with GBM.
Fig. 2.
Fig. 2.
Flowchart. Use of LEV and VPA during the study.
Fig. 3.
Fig. 3.
Kaplan–Meier curve of patients treated with chemoradiation with and without VPA for a minimum of 3 months. HR, hazard ratio.
See this image and copyright information in PMC

Comment in

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