belinostat

Belinostat is a histone deacetylase inhibitor (HDAC inhibitor) marketed under the brand name Beleodaq. It is a synthetic hydroxamic acid that acts as a pan-HDAC inhibitor, affecting multiple HDAC enzymes in class I and II. Inhibiting these enzymes increases acetylation of histones and other proteins, leading to changes in gene expression that can promote cell cycle arrest, differentiation, and apoptosis of malignant cells.

Medical use and regulatory status

Belinostat is approved in the United States for adults with relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single-agent therapy. It is used after prior systemic therapy and is administered intravenously. The approval is based on melanoma and lymphoma studies showing activity in PTCL, with ongoing research exploring broader indications and combination regimens.

Administration and dosing

Belinostat is given as an intravenous infusion once daily on Days 1 through 5 of a 21-day cycle. Dosing is described in the official labeling and may vary by body surface area and clinical factors; clinicians follow specific guidelines to ensure safe administration.

Adverse effects and safety

Common adverse effects include fatigue, nausea, diarrhea, vomiting, constipation, anorexia, fever, and cytopenias such as anemia and thrombocytopenia. Hepatotoxicity and QT interval prolongation have been reported, and liver function tests should be monitored during treatment. Other risks may include electrolyte disturbances and infection due to immune suppression.

Pharmacology and pharmacokinetics

Belinostat is metabolized primarily by hepatic pathways, including glucuronidation, with excretion of metabolites in urine and feces. The pharmacokinetic profile supports its short dosing window within a 21-day cycle, as used in PTCL therapy.