title: Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma.
abstract: OBJECTIVE
  Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS).
  
  
  METHODS
  Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS.
  
  
  RESULTS
  The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P < 0.01). Median OS was 42.2 and 20.3 months in the VPA use and non-use groups, respectively (P < 0.01; hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.18-0.74). Median PFS was 22.7 and 11.0 months in the VPA use and non-use groups, respectively (P = 0.099; HR, 0.62; 95% CI, 0.36-1.09).
  
  
  CONCLUSIONS
  VPA use during radiotherapy for glioma is associated with delayed hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Kuwabara
authors.affiliation: Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suehiro
authors.affiliation: Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamashita
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan. akiki@m.ehime-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Neurosurgery, Ehime Prefecture Central Hospital, 83 Kasuga-cho, Matsuyama, Ehime, 790-0024, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ohue
authors.affiliation: Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Araki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced / Q000517:prevention & control*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000628:therapy*; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000628:therapy*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D014635:Valproic Acid / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Hair loss; High-grade glioma; Radiotherapy; Valproic acid