Arsenic trioxide as first-line treatment for acute promyelocytic leukemia

Abstract

The history, clinical pharmacology and toxicities, and role of arsenic trioxide as a first-line agent for treating acute promyelocytic leukemia (APL) are described. APL is most often characterized by the hallmark reciprocal translocation between chromosomes 15 and 17, leading to the fusion of the promyelocytic gene and retinoic acid receptor alpha. Arsenic's therapeutic utility as an antileukemic agent was first described in the late 18th century. Arsenic trioxide demonstrates a dual, dose-dependent mechanism of action and can induce both partial myeloid differentiation and apoptosis. Arsenic trioxide is generally well tolerated, with reversible toxicities rarely requiring discontinuation of therapy. Toxicities associated with arsenic trioxide include leukocytosis, Q-T interval prolongation, APL differentiation syndrome, and hepatotoxicity. Since 2000, arsenic trioxide has been used as the standard of care for relapsed APL, with remission rates greater than 80% as a single agent. In an attempt to maximize disease-free survival and minimize relapse rates in patients with APL, arsenic trioxide is now being investigated as first-line therapy in the management of APL, with several studies showing promising outcomes. When used alone or in combination with tretinoin, the rates of complete remission have exceeded 85%, with high rates of molecular remission. Arsenic trioxide, alone or in combination with tretinoin, as first-line therapy in newly diagnosed APL has resulted in high rates of complete remission and molecular remission. Arsenic trioxide combined with tretinoin has shortened the time to achieve complete remission and lengthened disease-free survival, findings that suggest the usefulness of the regimen as first-line treatment for APL.