title: Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme.
abstract: BACKGROUND
  To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation.
  
  
  METHODS
  A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months. Cox-regression survival analysis was performed on 165 patients receiving chemoradiation with temozolomide of whom 108 receiving this in combination with VPA for at least 3 months.
  
  
  RESULTS
  Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on monotherapy. Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status.
  
  
  CONCLUSIONS
  Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.
authors.affiliation: Neuro-oncology Unit, Department of Neurology,Medical Center Haaglanden, The Hague, The Netherlands. mkerkhof85@gmail.com
authors.forename: Melissa
authors.initials: M
authors.lastname: Kerkhof
authors.forename: Janneke C M
authors.initials: JC
authors.lastname: Dielemans
authors.forename: Melanie S
authors.initials: MS
authors.lastname: van Breemen
authors.forename: Hanneke
authors.initials: H
authors.lastname: Zwinkels
authors.forename: Robert
authors.initials: R
authors.lastname: Walchenbach
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Taphoorn
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Vecht
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011379:Prognosis; D012189:Retrospective Studies; D012640:Seizures / Q000209:etiology / Q000401:mortality* / Q000517:prevention & control; D015996:Survival Rate; D000077204:Temozolomide; D014635:Valproic Acid / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D018906:Antineoplastic Agents, Alkylating; D000077287:Levetiracetam; D014635:Valproic Acid; D003606:Dacarbazine; D000077204:Temozolomide; D010889:Piracetam
keywords: epilepsy; glioblastoma multiforme; levetiracetam; survival; valproic acid