Arsenic trioxide: its use in the treatment of acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) represents approximately 10-15% of all adult cases of acute myeloid leukemia and is characterized by a unique genetic abnormality and frequent association with a severe hemorrhagic diathesis. An arsenic trioxide formulation for intravenous infusion has been developed and is currently licensed for the induction of remission and consolidation in adult patients with relapsed/refractory APL. Several studies have shown that arsenic trioxide is highly effective in the treatment of relapsed/refractory patients with APL, achieving remission rates of >80%, high rates of molecular remission, and durable periods of disease-free survival. Furthermore, recent studies indicate that arsenic trioxide may also have a role in the treatment of newly diagnosed patients, either as a single agent or in combination with tretinoin. These studies suggest a synergistic effect when arsenic trioxide and tretinoin are administered in combination, reducing the time to complete remission and rapidly reducing promyelocytic leukemia/retinoic acid receptor-α protein transcripts. Arsenic trioxide is generally well tolerated with a manageable adverse-event profile. The most common adverse events occur during the induction cycle and are often associated with the APL differentiation syndrome. Other common adverse events include leucocytosis, prolongation of the QT/corrected QT interval, peripheral neuropathy, neutropenia, thrombocytopenia, hyperglycemia, and hypokalemia.