Arsenic is a member of group Va of the periodic table. Arsenic trioxide (As2O3) is a white or transparent solid in the form of crystalline powder that resembles sugar. It has no odor or taste. It has low solubility in water; however, it dissolves readily in dilute hydrochloric solutions. It forms whenever elemental metallic arsenic is heated to high temperatures or burned. Arsenic trioxide can be absorbed by the digestive system and can cause acute poisoning when overdosed.

 

Despite the well known toxicity of arsenic, arsenic trioxide has been used medicinally for over 2000 years. Ancient Chinese used arsenic, also known as ‘‘Pi Shuang’’ in traditional Chinese medicine, to treat cancer and other conditions. The use of arsenic resurged when a medical group in Harbin, China, found that a crude intravenous preparation of arsenic trioxide, named Ailing-1, induced a high remission rate in acute promyelocytic leukemia (APL). The results were confirmed in a collaborative project between Harbin and Shanghai. This rediscovery of the therapeutic efficacy of arsenic in leukemia was an important milestone in the treatment of APL.

 

Intravenous arsenic trioxide is currently used to treat relapsed APL patients in the U.S. and the rest of the world except Hong Kong, where oral arsenic is used. Clinical studies have shown that complete remission rates between 78%-100% are obtained with intravenous arsenic trioxide treatment. However, there are many down sides associated with the intravenous formulation, including severe cardiac toxicity. This is because intravenous arsenic delays cardiac repolarisation by blocking repolarisation channels and prolongs the action potential duration in cardiac muscle. The cost of intravenous arsenic trioxide is inordinately high (about US$50,000 dollars a month), which makes this life-saving medication out of reach of leukemia patients in developing countries. Furthermore, there are also high hospitalization costs associated with intravenous arsenic trioxide.