title: Valproic acid was well tolerated in heavily pretreated pediatric patients with high-grade glioma.
abstract: Valproic acid (VPA) inhibits histone deacetylase and has been reported to induce apoptosis in glioma. We report 44 heavily pretreated pediatric patients with high-grade glioma or diffuse intrinsic pontine glioma who received VPA as oral continues maintenance treatment with individual dose adaptation. The tumor status when starting the drug was: no measurable disease in 12, measurable but stable disease in 12, and measurable progressive disease in 22 patients. Average trough blood levels of VPA were 99 mg/l. The most frequent complaint was somnolence (three patients), but no severe toxicity was reported. One relapse patient responded, early progression of disease was observed in three frontline patients and in six relapsed patients. Median overall survival duration for all patients was 1.33 years, with large differences between first-line (5-year overall survival, 44%) and relapse therapy (5-year overall survival, 14%). This shows that valproate is safe in this patient population. The moderate tumor efficacy encourages studying the drug further as an element of multi-agent protocols.
authors.affiliation: Children's Cancer Hospital, Department of Pediatrics, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, USA. jwolff@mdanderson.org
authors.forename: Johannes E A
authors.initials: JE
authors.lastname: Wolff
authors.forename: Christof
authors.initials: C
authors.lastname: Kramm
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Kortmann
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Norbert
authors.initials: N
authors.lastname: Jorch
authors.forename: Astrid
authors.initials: A
authors.lastname: Gnekow
authors.forename: Pablo Hernáiz
authors.initials: PH
authors.lastname: Driever
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D016019:Survival Analysis; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid