New York, November 5, 1998 -- Arsenic, a notorious poison, may be on the verge of overcoming its bad reputation. Two years ago, Chinese researchers reported that low doses of arsenic trioxide induced remission in patients with acute promyelocytic leukemia (APL), prompting physicians in the West to undertake their own pilot study.
Researchers at Memorial Sloan-Kettering Cancer Center have now become the first investigators in the Western world to show that arsenic effectively induces remission in patients who have relapsed with APL, a potentially fatal type of cancer that affects the blood and bone marrow. The findings are reported in the November 5 issue of the New England Journal of Medicine.
"We now know that arsenic can safely bring patients with APL into remission, which may ultimately give them a second chance at life," said Dr. Raymond P. Warrell, Jr., the senior author of the study and a leukemia specialist at Memorial Sloan-Kettering Cancer Center.
In the pilot study, 12 patients who had relapsed from conventional therapy were treated with low doses of arsenic trioxide. Eleven of the 12 patients achieved remission anywhere from 12 to 39 days after treatment started, experiencing only mild side effects.
The single patient who failed to reach remission died from a complication related to the disease five days after arsenic treatment began and could not be evaluated in the study.
Once remission was achieved, each patient received a brief treatment break, which was followed with repeated courses of arsenic trioxide therapy every three to six weeks thereafter. After two cycles of therapy, the investigators conducted additional tests to determine whether any molecular evidence of leukemia remained. Three patients tested positive for molecular evidence of the disease and later relapsed with APL, while eight patients tested negative for molecular evidence of APL and remained in remissions that lasted as long as 10 months. To date, several patients have received up to six courses of arsenic treatment without experiencing cumulative side effects.
"Based on these highly sensitive molecular results, treatment with arsenic trioxide appears to exceed the effectiveness of any single drug to treat APL," said Dr. Steven Soignet, the lead author of the study. "Still, this is not a cure. More studies will tell us how truly effective arsenic trioxide will be over the long term."
Arsenic trioxide works by killing the cancerous cells that cause APL, including those that have become resistant to the most successful form of treatment -- a drug called all-trans retinoic acid that was also pioneered by Dr. Warrell. Several years ago, he and others showed that all-trans retinoic acid could be used with chemotherapy to treat many patients with APL because it forced cancer cells to mature and die normally. But despite
this improvement in therapy, about 30 percent of patients who receive all-trans retinoic acid develop resistance to it and relapse with the disease. Arsenic trioxide appears to bypass this resistance by forcing APL cells to partly mature, and then causing them to self-destruct.
"This finding shows that arsenic trioxide does not discriminate between APL that is resistant or not resistant to retinoic acid, which may mean that we can use it at the outset of treatment for patients with APL," said Dr. Soignet.
Clinical trials using arsenic trioxide to treat patients with APL are on-going at Memorial Sloan-Kettering and at several centers throughout the country. Next, the investigators will look at arsenic trioxide’s effectiveness in treating other types of cancers.
The research has been supported in part by the National Cancer Institute, the Food and Drug Administration, the American Cancer Society and by grants from the Lymphoma Foundation and PolaRx Biopharmaceuticals, Inc.
Memorial Sloan-Kettering Cancer Center is the world's oldest and largest institution devoted to patient care, research, and education in cancer. Throughout its long, distinguished history, the Center has played a leadership role in defining the standards of care for patients with cancer. In 1998, Memorial Sloan-Kettering was named the nation's best cancer center for the sixth consecutive year by U.S. News & World Report.
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