Organic Arsenic

History and Preclinical Development

Arsenic has been used to treat cancer for more than 2000 years. Concepts of modern chemotherapy derive from early 20th century studies of arsenic when it was a mainstay of cancer chemotherapy. For example, in the early 1930's, inorganic arsenic was used to treat chronic myelogenous leukemia (CML) with dramatic effects.

Inorganic arsenic (such as arsenic trioxide) has diverse effects on many tissues including the heart and cardiovascular system, gastrointestinal tract, kidneys, skin, nervous system, and blood and bone marrow. Inorganic arsenic is especially toxic to the liver, causing infiltration, central necrosis, and cirrhosis. Furthermore, inorganic arsenic causes cancer of the skin and lung in humans. When given at high doses, inorganic arsenic has also been associated with EKG abnormalities.

Unlike inorganic arsenic, preclinical studies show few serious toxicities associated with organic arsenic.

In vitro testing of darinaparsin (ZIO-101) detected activity against lung, colon, brain, melanoma, ovarian and kidney cancer. Moderate activity was detected against breast and prostate cancer.

Additionally, in vitro testing and in vivo testing in a leukemia animal model demonstrated substantial activity against hematological cancers (cancers of the blood). These include leukemia, lymphoma, myelodysplastic syndromes and multiple myeloma.

Clinical development plan

A Phase II clinical trial is underway in patients with liver cancer, leukemia/lymphoma and myeloma. A Phase I trial has also begun involving oral administration. Preliminary results have been reported from the solid tumor trial on 37/40 patients where a variety of patients achieved a best response of stable disease. In the hematological trial, data show evidence of anti-leukemia activity in persons with advanced acute myelogenous leukemia (AML).

For more information regarding treatment centers, please visit our clinical trials page.