Vorinostat: A novel therapy for the treatment of cutaneous T-cell lymphoma.
OBJECTIVE
The pharmacology, pharmacokinetics, clinical efficacy, safety, adverse effects, dosage and administration, and role in therapy of vorinostat in the treatment of cutaneous T-cell lymphoma (CTCL) are reviewed.


CONCLUSIONS
Vorinostat is a novel histone deacetylase (HDAC) inhibitor approved for the treatment of advanced CTCL. Its primary biochemical mechanism is to correct an aberrant balance between acetylated and deacetylated histones, the proteins involved in chromatin structure and organization. Vorinostat is metabolized and excreted following glucuronidation by the uridine diphosphate glucuronosyl-transferase (UGT) enzyme system. Polymorphisms in the gene encoding for this enzyme system, UGT1A1, may be an important predictor of vorinostat toxicity and response levels in individual patients. Vorinostat is not metabolized by and does not inhibit the cytochrome P-450 isoenzyme system, and only two drug interactions have been noted with vorinostat: warfarin and valproic acid or other HDAC inhibitors. In two Phase II studies, patients with CTCL treated with oral vorinostat demonstrated significant reductions in skin lesions and decreased disease progression. The overall response rate was approximately 30%, including one complete response and a time to response of approximately 10 weeks. At the approved 400-mg, once-daily dose, vorinostat was well tolerated, with the most common grade 1 or 2 adverse events being fatigue, nausea, and diarrhea. More-severe toxicities included thrombocytopenia, fatigue, and nausea and occurred in less than 6% of patients.


CONCLUSIONS
Vorinostat, a novel HDAC inhibitor, is efficacious and well tolerated in patients with CTCL and is being investigated for its efficacy and safety in other types of cancers and as a part of combination therapy.
Kavanaugh
Shannon M
SM
School of Pharmacy, University of Wisconsin, Madison. USA.
Kavanaugh
Shannon A
SA
White
Lisa A
LA
Kolesar
Jill M
JM
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008954:Models, Biological; D012878:Skin Neoplasms / Q000188:drug therapy*; D000077337:Vorinostat
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat