Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat

摘要

Epigenetic regulation of gene transcription by small molecule inhibitors of histone deacetylases (HDAC) is a novel cancer therapy. Vorinostat (Zolinza?) is the first FDA approved HDAC-inhibitor for treatment of patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. 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 patients with CTCL including large cell transformation and Sézary syndrome (SS). The common side effects of vorinostat, similar in all studies, included gastro-intestinal symptoms, fatigue, and thrombocytopenia and the most common serious events were thrombosis. Vorinostat, in combination with other agents such as radiation therapy and chemotherapy, have shown synergistic or additive effects in a variety of cancers in clinical trials.