Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma

Abstract

Epigenetic regulation of gene transcription by small-molecule inhibitors of histone deacetylases (HDACs) is a novel cancer therapy. Vorinostat (suberoylanilide hydroxamic acid) is the first FDA-approved HDAC inhibitor for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL). Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. In two Phase II trials, vorinostat 400 mg/day was safe and effective with an overall response rate of 24 – 30% in refractory advanced patients with CTCL including large cell transformation and Sézary syndrome. The common side effects of vorinostat, which are similar in all studies, include gastrointestinal symptoms, fatigue and thrombocytopenia and the most common serious event was thrombosis.

Keywords::

• cutaneous T-cell lymphoma
• histone deacetylase inhibitors
• mycosis fungoides
• Sézary syndrome
• suberoylanilide hydroxamic acid
• vorinostatv

Disclosure

M Duvic has received clinical and basic support from Aton/Merck for conducting clinical trials and NIHK24CA86815. J Vu declares no competing financial interest. This article was independently commissioned and no fee was received for preparation of the manuscript.

Notes