Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma.
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.
Duvic
Madeleine
M
University of Texas MD Anderson Cancer Center, Department of Dermatology, Houston, TX 77030, USA. mduvic@mdanderson.org
Vu
Jenny
J
D000284:Administration, Oral; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015507:Drugs, Investigational; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D007150:Immunohistochemistry; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D000077337:Vorinostat
D015507:Drugs, Investigational; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat