Washington (H24N). The Food and Drug Administration (FDA) approved on Tuesday Arsenic trioxide, a former insect poison, to treat acute promyelocytic leukemia, a rare and often fatal form of leukemia that is resistant to chemotherapy and strikes about 1,500 Americans a year.

In 1998, researchers at Memorial Sloan-Kettering Cancer Center in New York City confirmed Chinese studies that proved that small doses of arsenic, which has also been used to treat syphilis, are extremely effective at putting acute promyelocytic leukemia (APL) into remission without harming healthy blood cells. An intravenous form of arsenic trioxide called Trisonex has been developed by Cell Therapeutics Inc. of Seattle and will be available within three weeks.

According to Steven Hirschfeld, MD, a medical officer at the FDA, Chinese scientists noticed in the late 1970s that traditional Chinese healers gave leukemia patients a paste that sometimes worked against the disease. Arsenic trioxide was found to be the active ingredient. Successful studies at the Shanghai Institute of Hematology with intravenous forms of the compound attracted the attention of scientists at Memorial Sloan-Kettering, who began their own research in 1997.

The investigators at Memorial Sloan-Kettering gave the drug to 40 patients with APL, and 28 of them achieved complete remissions, some of which have lasted several years. "To have a 70 percent response rate in patients who have failed conventional treatment is an exceptionally good result," said David Scheinberg, MD, chief of Leukemia Treatment at Memorial Sloan-Kettering, in an article in the global edition of Doctor's Guide. Steven Soignet, MD, the lead author of the Memorial Sloan-Kettering study who was quoted in the same article, cautioned that arsenic trioxide could not yet be considered a cure for APL and that further studies were needed to determine its effectiveness over the long term.

Normal blood is formed of red cells, white cells and platelets in balanced numbers. These blood elements are principally made in the bone marrow from starter cells (called stem cells), which grow in stages into the three different blood components. Leukemia is a form of cancer of the bone marrow that causes too many white cells to form from the stem cells and to stop developing before they are fully mature. These immature forms take up so much space in the bone marrow that not enough red blood cells and platelets are formed. There are several kinds of white blood cells (lymphocytes, monocytes and the myelocytes), and the type of leukemia, what special problems it causes, and the way it is treated are determined by the kind of white blood cell that is overproduced. Patients with acute promyelocytic leukemia have too many myelocytes.

APL is caused by a genetic mutation on genes 15 and 17. As many as a third of patients who receive conventional chemotherapy for APL do not respond or relapse quickly, and until a few years ago there were no other treatment options. In the mid-90s, both Western and Chinese researchers decided to concentrate on the mutation itself and discovered that, when genes 15 and 17 changed places, the result was the formation of a double protein that blocked the use of retinoic acid (a form of vitamin A also used to treat acne and rejuvenate skin) which helps healthy white blood cells form and mature. The protein also interferes with clotting, and APL patients often die of hemorrhages in their brains or digestive tracts.

Giving patients retinoic acid forced the immature white blood cells to mature, live out their full lifespan and die naturally (apoptosis) and increased the overall survival rate from 51 percent to 81 percent, but there was still a significant group that relapsed quickly or did not respond at all.

Arsenic filled that gap. The Chinese researchers discovered that it caused apoptosis as retinoic acid did, but also worked on the other half of the protein that interfered with clotting. It has produced good results both in patients who respond to retinoic acid and those that don't, does not harm other cells in the body and is more effective in the treatment of APL than any other single agent.

A complete course of therapy with Trisonex will cost between $12,000 and $16,000, and researchers around the country are investigating its usefulness in treating other types of cancer.

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