Vorinostat

Vorinostat is an HDAC inhibitor currently marketed in the United States and other countries for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) who have progressive disease, persistent, or recurrent disease following two systemic therapies. Vorinostat inhibits the enzymatic activity of Class I (HDAC1, HDAC2, HDAC3) and Class II (HDAC6) HDACs at nanomolar concentrations (IC₅₀<86 nM). A clinical study of vorinostat in patients with stage Ib and higher CTCL, who had failed to two systemic therapies (one containing bexarotene), demonstrated a 30 % overall objective response. An additional study in refractory CTCL patients demonstrated a similar response rate of 31 %. The most common adverse reactions (incidence C20 %) associated with vorinostat treatment are diarrhea, fatigue, nausea, thrombocytopenia, anorexia, and dysgeusia. Vorinostat is being actively investigated in other solid and hematological malignancies as monotherapy treatment or in combination with other chemotherapies. The clinical pharmacology of vorinostat is reviewed within, including serum and urine pharmacokinetic data, special population data, and data regarding drug–drug interactions. QTc assessment data are also included. Data from peer-reviewed sources were identified through a literature search (as of July 25, 2012) using the MedLine®, Web of Science®, and Biosis Previews® databases. Key words used to identify articles of interest included vorinostat, suberoy- lanilide hydroxamic acid, SAHA, pharmacokinetics, and interaction.