Influence of valproic acid on outcome of high-grade gliomas in children

Anticancer Res. Jul-Aug 2008;28(4C):2437-42.

Abstract

Background: Chemotherapy has limited effects in the treatment of high-grade gliomas (HGGs). Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, may sensitize HGGs to radiochemotherapy. As the drug has been given frequently as an antiepileptic drug, a retrospective analysis was conducted to ensure relevant information was not missed before a prospective study was launched.

Materials and methods: An analysis of 66 pediatric patients (range, 1-19 years of age) with glioblastoma multiforme (GBM) (n=40) or anaplastic astrocytoma (AA) (n=26) was retrospectively conducted for predictors of survival and response and for effects of VPA on outcome or toxicity.

Results: The overall survival (OS) was better for AA (p=0.0114) and complete resection (p<0.00005) and event-free survival (EFS) was better for complete resection (p=0.0049). Nine patients received VPA (for seizure) plus further oncological treatment. The most severe adverse effect was a pulmonary embolism (n=1); no other severe side-effects were noted. The response to nonsurgical treatment after 8 weeks was: complete response (CR): 0, partial response (PR): 3, stable disease (SD): 4, progressive disease (PD): 2. Some of the patients with SD responded later resulting in best response: CR:0, PR:5, SD:2, PD:2.

Conclusion: Treatment with VPA plus radiochemotherapy is well tolerated with an encouraging response rate.

MeSH terms

  • Adolescent
  • Adult
  • Astrocytoma / drug therapy*
  • Astrocytoma / surgery
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / surgery
  • Humans
  • Infant
  • Male
  • Retrospective Studies
  • Valproic Acid / adverse effects
  • Valproic Acid / therapeutic use*

Substances

  • Valproic Acid