pazopanib + vorinostat

pazopanib + vorinostat is a combination therapy investigated for the treatment of advanced malignancies. It consists of vorinostat (Zolinza), an orally active histone deacetylase (HDAC) inhibitor, and pazopanib (Votrient), an orally active multi-targeted tyrosine kinase inhibitor. The combination was evaluated in a Phase I dose-escalation trial (NCT01339871) at the M.D. Anderson Cancer Center, which established a recommended Phase II dose of 300 mg vorinostat and 600 mg pazopanib daily. Vorinostat works by inhibiting HDAC enzymes (primarily HDAC1, 2, 3, and 6), leading to the accumulation of acetylated histones and proteins, which induces cell cycle arrest and apoptosis. Pazopanib targets vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), platelet-derived growth factor receptors (PDGFR-alpha and -beta), and the stem cell factor receptor (c-Kit), thereby inhibiting angiogenesis and tumor cell growth. This combination has shown particular clinical activity in patients with TP53-mutant cancers, including metastatic sarcoma and colorectal cancer.

Other names

vorinostat and pazopanibpazopanib and vorinostat