Valproic Acid Beneficial in Glioblastoma, But Not Low-Grade Glioma

brain tumor
brain tumor
Interestingly, the risk of death and tumor progression was increased in low-grade gliomas.

Valproic acid appears to be effective in improving survival in grade IV glioblastoma, however it may be detrimental to histological progression and survival in lower grade gliomas.

The antiepileptic drug has properties of a histone deacetylase inhibitor (HDACi), which are of increasing interest as anticancer agents.

In this study, Navid Redjal, MD, of Massachusetts General Hospital, and colleagues aimed to determine the effects of valproic acid on grade II, III, and IV gliomas through a retrospective analysis of 359 glioma patients who were treated with temozolomide and an antiepileptic drug (valproic acid or other) between January 1997 and June 2013.

After adjusting for confounders, valproic acid was associated with a 28% decrease in hazard of death (P=0.031) and 28% decrease in hazard of progression or death (P=0.015) in grade IV glioblastoma. Valproic acid dose was also found to correlate with reduced hazard of death by 7% (P=0.002) and reduced hazard of progression or death by 5% (P<0.001).

Interestingly, valproic acid was associated with a 118% increase in tumor progression or death (P=0.014) in grade II and III gliomas, and each additional 100g of valproic acid raised the hazard by 4%, although this was not statistically significant (P=0.064). Grade II and III glioma patients taking valproic acid also had 2.17 times the risk of histological progression (P=0.020), although this too was not statistically significant after adjusting for confounders.

The effects of treatment with valproic acid in gliomas will need to be confirmed through future studies, the authors concluded.


Redjal N, Reinshagen C, Le A, et al. Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide. J Neurooncol. 2016;127(3):505-14.