Belinosta Introduction
Belinostat is an intravenously administered histone deacetylase inhibitor and antineoplastic agent that is approved for use in refractory or relapsed peripheral T cell lymphoma. Belinostat is associated with moderate rate of minor serum enzyme elevations during therapy and has been reported to cause clinically apparent fatal, acute liver injury.
Background
Belinostat (be lin' oh stat) is a parenterally administered small molecule inhibitor of histone deacetylase which acts by preventing removal of acetyl groups from histones. Accumulation of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. Malignant cells and particularly malignant T cells are particularly sensitive to the effects of inhibition of histone deacetylases. In open label studies in patients with refractory or relapsed peripheral T cell lymphoma (PTCL), monotherapy with belinostat yielded an overall response rate of 26% and some responders had long term remissions and were able to undergo hematopoietic cell transplantation. Belinostat was approved for use in the United States in 2014 as monotherapy for refractory or relapsing peripheral T cell lymphoma. Belinostat is available as a lyophilized powder for reconstitution in 500 mg single use vials under the commercial name Beleodaq. The recommended dose is 1 gm/m2 given intravenously on days 1 to 5 in 21 day cycles, which are repeated until there is disease progression or unacceptable toxicity. Side effects are common, but usually mild-to-moderate in severity, and include nausea, fatigue, fever, anemia, neutropenia, thrombocytopenia, constipation, rash, edema, cough and pruritus. Side effects lead to early discontinuation in up to 20% of patients. Severe adverse events can include marked neutropenia, thrombocytopenia, serious infections, sepsis, tumor lysis syndrome and acute liver failure.
