Journal of Neuro-Oncology

, 90:309

Valproic acid was well tolerated in heavily pretreated pediatric patients with high-grade glioma

  • Johannes E. A. Wolff
  • Christof Kramm
  • Rolf-Dieter Kortmann
  • Torsten Pietsch
  • Stefan Rutkowski
  • Norbert Jorch
  • Astrid Gnekow
  • Pablo Hernáiz Driever
Clinical Study - Patient Study


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.


Valproic acid Glioblastoma Anaplastic astrocytomas Pontine glioma Child Adolescent 


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Johannes E. A. Wolff
    • 1
    • 2
    • 3
  • Christof Kramm
    • 4
  • Rolf-Dieter Kortmann
    • 5
  • Torsten Pietsch
    • 6
  • Stefan Rutkowski
    • 7
  • Norbert Jorch
    • 8
  • Astrid Gnekow
    • 9
  • Pablo Hernáiz Driever
    • 10
  1. 1.Children’s Cancer Hospital, Department of Pediatrics, Unit 87The University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of BiostatisticsThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Pediatric Hematology and OncologyUniversity of RegensburgRegensburgGermany
  4. 4.Department of Pediatric OncologyMartin-Luther University Halle-WittenbergHalleGermany
  5. 5.Department of Radiation OncologyUniversity of LeipzigLeipzigGermany
  6. 6.Department of NeuropathologyUniversity of BonnBonnGermany
  7. 7.Children’s University HospitalUniversity of WuerzburgWuerzburgGermany
  8. 8.Department of PediatricsKrankenanstalten GileadBielefeldGermany
  9. 9.Department of PediatricsKlinik für Kinder und JugendlicheAugsburgGermany
  10. 10.Department of Pediatric Oncology and HematologyCharité-Universitätsmedizin BerlinBerlinGermany

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