The Safety Profile of Vorinostat (Suberoylanilide Hydroxamic Acid) in Hematologic Malignancies: A Review of Clinical Studies

Cancer Treat Rev. 2016 Feb;43:58-66. doi: 10.1016/j.ctrv.2015.04.003. Epub 2015 Apr 9.

Abstract

Histone acetyltransferases and histone deacetylases (HDACs) are multifunctional enzymes that posttranslationally modify both histone and nonhistone acetylation sites, affecting a broad range of cellular processes (e.g., cell cycle, apoptosis, and protein folding) often dysregulated in cancer. HDAC inhibitors are small molecules that directly interact with HDAC catalytic sites preventing the removal of acetyl groups, thereby counteracting the effects of HDACs. Since the first HDAC inhibitor, valproic acid, was investigated as a potential antitumor agent, there have been a number of other HDAC inhibitors developed to improve efficacy and safety. Despite significant progress in the management of patients with hematologic malignancies, overall survival is still poor. The discovery that HDACs may play a role in hematologic malignancies and preclinical studies showing promising activity with HDAC inhibitors in various tumor types, led to clinical evaluation of HDAC inhibitors as potential treatment options for patients with advanced hematologic malignancies. The Food and Drug Administration has approved two HDAC inhibitors, vorinostat (2006) and romidepsin (2009), for the treatment of cutaneous T-cell lymphoma. This review highlights the safety of HDAC inhibitors currently approved or being investigated for the treatment of hematologic malignancies, with a specific focus on the safety experience with vorinostat in cutaneous T-cell lymphoma.

Keywords: Clinical trial; HDAC; Hematologic malignancies; Histone deacetylase inhibitors; Safety; Vorinostat.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Depsipeptides / pharmacology*
  • Disease Management
  • Hematologic Neoplasms* / metabolism
  • Hematologic Neoplasms* / pathology
  • Histone Acetyltransferases* / antagonists & inhibitors
  • Histone Acetyltransferases* / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Lymphoma, T-Cell, Cutaneous* / metabolism
  • Lymphoma, T-Cell, Cutaneous* / pathology
  • Protein Folding / drug effects
  • Treatment Outcome
  • Vorinostat

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Vorinostat
  • romidepsin
  • Histone Acetyltransferases
  • Histone Deacetylases