CLINICAL TRIAL: PI &PHARMACOKINETIC STUDY OF DRUG FOR SOLID TUMORS &LYMPHOMAS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase 1, multicenter trial to determine the pharmacokinetic disposition of vorinostat is patients with varying degrees of hepatic dysfunction. Vorinostat is an inhibitor of Histone deacetylases (HDAC), enzymes that catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. HDAC inhibitors can induce tumor cell growth arrest, differentiation, or apoptosis in vitro and inhibit tumor growth in animals and the eventual goal is to use this drug to treat solid tumors, and therefore tumor progression will be a secondary aim of the study. Vorinostat has recently been approved by the US FDA (400 mg PO QD) for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat has a short half life of less than 2 hours. The major pathways of metabolism of vorinostat involve glucuronidation and There are no data regarding the appropriate use of vorinostat in patients with hepatic dysfunction.