Vorinostat

November 1, 2006

This agent targets the overexpression of histone deacetylase (HDAC) or the aberrant recruitment of HDACs to oncogenic transcription factors in cancer cells. Vorinostat was approved on October 6, 2006, for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent, or recurrent disease following 2 systemic therapies.

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VorinostatMerckFirst-in-class histone deacetylase inhibitor approved for cutaneous T-cell lymphoma

This agent targets the overexpression of histone deacetylase (HDAC) or the aberrant recruitment of HDACs to oncogenic transcription factors in cancer cells. Vorinostat was approved on October 6, 2006, for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent, or recurrent disease following 2 systemic therapies.

Safety. Pulmonary embolism and deep vein thrombosis have been reported in association with vorinostat. Patients receiving vorinostat therapy should be monitored for the pertinent signs and symptoms of these conditions. Dose-related thrombocytopenia and anemia have occurred with vorinostat and may require dose modification or discontinuation of therapy. Vorinostat therapy has been associated with gastrointestinal disturbances (eg, nausea, vomiting, and diarrhea). As such, patients may require antiemetics, antidiarrheals, and/or fluid or electrolyte replacement when taking the drug. Hyperglycemia has been observed in association with vorinostat therapy, necessitating the potential adjustment of diet and/or dosing. Vorinostat has been associated with prolongation of the QTc interval. Taking this into consideration, patients' electrolytes and electrocardiograms (ECGs) should be monitored at baseline and periodically during treatment. The most common adverse events associated with vorinostat therapy include diarrhea, fatigue, nausea, thrombocytopenia, anorexia, and dysgeusia.

Dosing. The recommended dose of vorinostat is 400 mg orally once daily with food. If a patient is intolerant to therapy, the dose may be reduced to 300 mg once daily with food. If necessary, the dose may be further reduced to 300 mg once daily with food for 5 consecutive days each week.