The Pharmaceutical Benefits Scheme (PBS) listing for arsenic trioxide has recently extended to include the first-line treatment of acute promyelocytic leukaemia (APL). Well known for its toxicity and carcinogenic properties, the use of arsenic in the treatment of cancer may seem paradoxical. Although the exact mechanism of action is not well understood, arsenic acts on many pathways to induce apoptosis and differentiation, and to inhibit proliferation and angiogenesis.

A 2013 study demonstrated a 2-year event-free survival of 97% in APL patients treated with arsenic trioxide plus all-trans retinoic acid (ATRA) compared to 86% for patients treated with ATRA plus chemotherapy. While the clinical efficacy of these protocols is thought to be similar, improved survival rates in arsenic-treated patients may be the result of a more favourable haematological toxicity profile.

Serious adverse effects, however, are not uncommon. APL differentiation syndrome is a life-threatening complication that occurs in around 25% of patients receiving arsenic induction therapy. Signs and symptoms may include fever, dyspnoea, respiratory distress, pulmonary oedema, and leukocytosis. Serious cardiac conduction disorders may also be observed; prolongation of the QT interval is very common, and torsade de pointes and ventricular tachycardia are common. Symptoms of acute arsenic toxicity require discontinuation of arsenic therapy; chelation and other anti-arsenical therapies should also be considered.

References:

  1. Litzow MR. Arsenic trioxide . Expert Opin Pharmacother. 2008; 9(10): 1773-85.
  2. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. New Engl J Med. 2013; 369(2): 111-21.
  3. Miller WH, Schipper HM, Less JS, Singer J, Waxman S. Mechanisms of action of arsenic trioxide. Cancer Res. 2002; 62(14): 3893-903.
  4. Phenasen® (arsenic trioxide) Australian approved product information. Lane Cove West: Phebra Pty Ltd. Approved August 2015.
  5. Rogers JE, Yang D.Differentiation syndrome in patients with acute promyelocytic leukemia. J Oncol Pharm Practice. 2011; 18(1): 109-14.

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