NEW YORK, Nov 04 (Reuters Health) -- Low doses of a form of arsenic trioxide can safely bring about complete remission in patients with acute promyelocytic leukemia (APL) who have had relapses despite extensive prior treatment, US researchers report.
These findings confirm those of two Chinese studies, according to the researchers, Dr. Steven L. Soignet of Memorial Sloan-Kettering Cancer Center in New York, and colleagues. The researchers report their results in the November 5th issue of The New England Journal of Medicine.
Soignet and colleagues tested arsenic trioxide in 12 APL patients who had had multiple relapses and were not responding to traditional chemotherapy, bone marrow transplants, or treatment with all-trans-retinoic acid and related drugs -- medications that usually bring about remission. The researchers gave the patients intravenous doses of arsenic trioxide ranging from 0.06 to 0.2 milligrams per kilogram of body weight daily, until the patients no longer had visible leukemic cells in their bone marrow.
In acute leukemia, the body overproduces abnormal, nonfunctional white blood cells that virtually take over the bone marrow, crowding out the normal, functional white blood cells usually found there.
After 12 to 39 days of treatment, 11 of the 12 patients had complete, symptom-free remission, Soignet and colleagues report. One patient died of complications of the disease 5 days into the trial.
Remission lasted from between 1 month to more than 9 months, and all 11 patients completed at least one additional course of treatment after the initial remission. Three of the 11 relapsed during the second course of treatment, however. And 2 of these patients later died of leukemia, according to the researchers.
The relatively low doses of arsenic trioxide the patients were given caused "few serious adverse reactions," Soignet's team reports. The most commonly reported side effects included rash, lightheadedness, fatigue, and muscle and bone pain.
"These finding are especially important, since severe toxic reactions including... renal failure, have been observed after attempts to increase the dose beyond this range," they write.
Although compounds in the arsenic family have been used medicinally for thousands of years, and were used to treat chronic myelocytic leukemia until the 1930s, the mechanism by which arsenic trioxide brings about remission in APL patients is not entirely clear, the researchers note. Ultimately, the drug appears to cause the cancerous white blood cells to "commit suicide," they write.
Arsenic trioxide may have other promising uses, Dr. Robert E. Gallagher of Montefiore Medical Center, Bronx, New York, writes in an accompanying editorial.
Including arsenic trioxide in initial chemotherapy and all-trans-retinoic acid treatment for APL might improve outcomes, Gallagher notes. Preliminary findings from earlier laboratory studies suggest that the compound and related drugs may inhibit other types of tumor cells at safe doses.
SOURCE: The New England Journal of Medicine 1998;339:1341-1348, 1389-1391.
