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Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma

  • Pharmacoepidemiology and Prescription
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

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.

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Author’s contributions

SW and AT contributed to the design of the study, collected data, and wrote the manuscript. SS, DY, and SO facilitated the data collection. YK and MT performed the analyses. HA was involved in the review of the study design, protocol, and study report, and in the preparation of the manuscript. All authors reviewed and edited the paper.

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Authors and Affiliations

  1. Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan

    Shinichi Watanabe, Yui Kuwabara, Mamoru Tanaka, Akihiro Tanaka & Hiroaki Araki

  2. Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan

    Satoshi Suehiro & Daisuke Yamashita

  3. Department of Neurosurgery, Ehime Prefecture Central Hospital, 83 Kasuga-cho, Matsuyama, Ehime, 790-0024, Japan

    Shiro Ohue

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  1. Shinichi Watanabe
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Correspondence to Akihiro Tanaka.

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Watanabe, S., Kuwabara, Y., Suehiro, S. et al. Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma. Eur J Clin Pharmacol 73, 357–363 (2017). https://doi.org/10.1007/s00228-016-2167-1

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  • DOI: https://doi.org/10.1007/s00228-016-2167-1

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