Valproic Acid, Levetiracetam Do Not Improve Survival in Newly Diagnosed GBM

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Valproic acid and levetiracetam do not improve survival outcomes in patients with newly diagnosed glioblastoma, a study published online ahead of print in the Journal of Clinical Oncology has shown.1

Because several uncontrolled retrospective case series and a post hoc analysis have suggested an association between improved survival outcomes and valproic acid when added to temozolomide, researchers sought to evaluate whether antiepileptic drugs improve survival in patients with newly diagnosed glioblastoma. To do so, investigators conducted a pooled analysis of 4 contemporary randomized clinical trials in this patient population.

The 4 trials included AVAGlio (Avastin in Glioblastoma), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status), and Radiation Therapy Oncology Group 0825.

Results showed that valproic acid use at the start of chemoradiotherapy was not associated with improved progression-free or overall survival, nor was it associated with improved survival outcomes when taken both at the start of and after chemoradiotherapy.

Similarly, there was no associated between use of levetiracetam and improved outcomes.

“The results of this analysis do not justify the use of valproic acid or levetiracetam for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials,” the authors conclude.


1. Happold C, Gorlia T, Chinot O, et al. Does valproic acid or levetiracetam improve survival in glioblastoma? A pooled analysis of prospective clinical trials in newly diagnosed glioblastoma [published online ahead of print January 19, 2016]. J Clin Oncol. doi:10.1200/JCO.2015.63.6563.

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