Vorinostat for the treatment of cutaneous T-cell lymphoma

Vorinostat (suberoylanilide hydroxamic acid) is the first US FDA-approved histone deacetylase inhibitor for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphomas (CTCLs). In two Phase II trials, vorinostat was safe and effective at an oral dose of 400 mg/day, with an overall response rate of 24-30% in refractory advanced CTCL patients, including large-cell transformed mycosis fungoides and Sézary syndrome. Most patients with CTCL also experience significant itching relief with vorinostat therapy. Moreover, a recent follow-up study reported long-term safety and clinical benefits of vorinostat in heavily pretreated patients with CTCL, regardless of previous treatment failures. The most frequent side effects of vorinostat include gastrointestinal symptoms, fatigue and thrombocytopenia. These side effects are dose-related and reversible upon cessation of therapy. Translational studies have shown that vorinostat has in vitro and in vivo anti-tumor activities against CTCL, including selective induction of apoptosis in tumor T cells, inhibition of angiogenesis, suppression of signal transducer and activator of transcription proteins and upregulation of proapoptotic proteins. Further identification of predictive biomarkers of vorinostat will help to select patients most likely to benefit from treatment and develop better combination therapies for patients with CTCL.