title: Effect of valproic acid on the outcome of glioblastoma multiforme.
abstract: BACKGROUND
  Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor. It is a rapidly progressive, highly recurrent, fatal intracranial neoplasm, and the demand for novel treatment is urgent. Valproic acid (VPA) is a potential anticancer agent that belongs to a class of histone deacetylase (HDAC) inhibitors, targeting the epigenetic control of gene functions in cancer cells. This drug has been administered for the prevention or treatment of seizure disorder in GBM patients; therefore, a retrospective analysis may further our understanding of the effect of VPA on GBM patients.
  
  
  METHODS
  A retrospective analysis of 102 patients with GBM was conducted to study the effects of VPA on disease outcome. Tumor samples from seven patients receiving VPA treatment between the first and second operations were obtained in order to verify the HDAC inhibitory activity of VPA in these patients.
  
  
  RESULTS
  In univariate analysis, administration of VPA within 2 weeks of initial diagnosis seemed to confer a survival benefit. However, stratified analysis according to chemotherapy showed that VPA did not have significant impact on the GBM patients' overall survival. Analysis of tissue samples from these patients revealed that a small subset of patients had increased histone acetylation after VPA treatment.
  
  
  CONCLUSIONS
  VPA treatment, when administered according to a protocol targeting seizure control, may result in HDAC inhibition in a small subset of patients, but does not significantly affect overall patient survival. Early administration of VPA as an adjunct to temozolomide chemotherapy may have its merits, but the optimal dosing schedule and target serum level require further investigation.
authors.affiliation: Department of Neurosurgery, Chang-Gung Memorial Hospital and University, Tao-Yuan, Taiwan.
authors.forename: Hong-Chieh
authors.initials: HC
authors.lastname: Tsai
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
authors.forename: Chi-Neu
authors.initials: CN
authors.lastname: Tsai
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Huang
authors.forename: Pin-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Chen
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Lu
authors.forename: Shih-Tseng
authors.initials: ST
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014635:Valproic Acid; D051548:Histone Acetyltransferases