Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia

Abstract

Arsenic trioxide (ATO) is presently the most active single agent in the treatment of acute promyelocytic leukemia (APL). This review provides insights into the mode of action and the pharmacological properties of ATO, and summarizes the most relevant results of more than 20 treatment studies in relapsed or newly diagnosed APL published between 1997 and 2011. ATO acts by targeting multiple pathways in APL leading to apoptosis and myeloid differentiation. It induces complete remission without myelosuppression and causes only few adverse effects. In relapsed APL, ATO-based salvage therapy has been able to induce long-lasting remissions and possible cure in 50-81% of patients. In newly diagnosed APL, two main strategies are currently pursued. ATO is either included into induction therapy with the aim to minimize or eliminate chemotherapy, or it is incorporated as an additive into established first-line concepts with all-trans-retinoic acid and chemotherapy to reinforce their anti-leukemic efficacy. Recent results suggest a high efficacy of ATO in both concepts. In conclusion, experimental research and clinical studies have made contributions toward a better understanding of the molecular mechanisms induced by ATO in APL cells and have established this historic substance as an important candidate for the further improvement of APL therapy.

The 12-year follow-up of survival, chronic adverse effects, and retention of arsenic in patients with acute promyelocytic leukemia

“…Acute and chronic GVHD were defined and scored according to the Glucksberg and National Institutes of Health consensus criteria, respectively. [15][16][17] TRM was defined as death from any cause without evidence of relapse or progression of the original disease. Progressionfree survival (PFS) was defined as the interval from HSCT to either relapse or progression or death in remission (whichever came first).…”

Role of cysteine 288 in nucleophosmin cytoplasmic mutations: sensitization to toxicity induced by arsenic trioxide and bortezomib

“…9 It has also been postulated that the bortezomib-induced increases in ROS levels in tumor cells may be the basis for its synergy with other chemotherapeutic agents. 9,23 Arsenic trioxide (ATO) has emerged as the most active single agent in the treatment of acute promyelocytic leukemia, 24 and ATO-based therapies are being investigated in other cancers including other hematopoietic malignancies. [25][26][27][28][29] Although the mechanisms underlying ATO-induced cytotoxicity are not completely understood, ATO-mediated induction of ROS has been shown to reduce the membrane potential of mitochondria, enhance the release of cytochrome c and induce both caspasedependent and caspase-independent apoptosis.…”

Arsenic trioxide-induced QT interval prolongation: A case report

“…Lengfelder et al described arsenic trioxide as very potent and first line agent in treatment of APL. [7] Chiang et al studied the action of ATO on guinea pig papillary muscle and the study concluded that dose dependent IV infusion of ATO prolonged QT interval and action potential duration (APD). [8] The study suggested that Arsenic trioxide has direct effect on cardiac repolarisation and the drug must be administered with strict ECG monitoring.…”