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.

Darinaparsin Preclinical Development

In vitro 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.

Additionally, 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.

Clinical Development Plan

A Phase II trial is nearing completion in patients with primary liver cancer and advanced myeloma, a Phase II trial is ongoing in patients with lymphomas, and a Phase I oral trial is in progress. Preliminary results from previous trials have reported stable diseases in patients with solid tumors, MDS and CML. A complete remission and partial remissions were seen in patients heavily pretreated for Hodgkin’s and non-Hodgkin’s lymphomas.

Unlike inorganic arsenic, preclinical and clinical studies show little serious toxicities associated with organic arsenic, particularly the ECG abnormalities seen at high doses. Extensive ECG data has been collected as part of the darinaparsin development program and central tendency analysis revealed no significant drug effect on cardiac function comparable to inorganic arsenic.

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