September 27, 2000
WASHINGTON (AP) - A form of arsenic once used as insect poison won Food and Drug Administration approval Tuesday as a leukemia treatment after studies found small doses helped patients with a rare but deadly form of the disease.
The approval of Trisenox, the brand name for arsenic trioxide, marks the first official arsenic-based therapy in the United States in over 100 years - one that came when U.S. scientists noted China was having some success with a compound much of the world had abandoned.
At issue is the rare "acute promyelocytic leukemia," or APL, which strikes about 1,500 Americans a year. About 400 will not respond to, or will quickly relapse after, standard chemotherapy. These patients have had few options but to try standard therapy again in hopes of buying some time.
But in a study of Trisenox, 28 of the 40 patients given the drug intravenously went into remission - an impressive 70 percent response rate, the FDA said. How long remission lasts varies, cautions FDA medical officer Dr. Steven Hirschfeld, but a few have lasted several years.
"To have a 70 percent response rate in patients who have failed conventional treatment is an exceptionally good result," said Dr. David Scheinberg, leukemia chief at New York's Memorial Sloan-Kettering Cancer Center, which is responsible for arsenic trioxide's comeback.
Arsenic alone is a poison and can cause cancer, but arsenic-containing compounds have been used medically for more than 2,000 years. Ninteenth-century U.S. doctors tried arsenic to treat leukemia, but abandoned it with the discovery of radiation and chemotherapy.
In the late 1970s, Chinese scientists noticed traditional Chinese practitioners were giving leukemia patients an arsenic-containing paste that in some cases seemed to work, Hirschfeld said. Those scientists eventually figured out that arsenic trioxide was the beneficial ingredient, and hunted for intravenous forms. Successful Chinese studies attracted the attention of Sloan-Kettering, which began U.S. tests in 1997.
APL is a cancer where abnormal or immature white blood cells crowd out proper white cells and red blood cells in the bone marrow and blood. Arsenic trioxide apparently works like another common APL treatment, retinoic acid: Instead of killing cells, it causes those immature white cells to mature into normal cells, Scheinberg said. Scientists now are testing whether it might help certain other cancers, too.
It can cause very serious side effects, the FDA cautioned. The sudden increase of working white blood cells can cause inflammation and fluid accumulation, especially in the heart and lungs, that can be fatal. Twenty percent of patients who tested Trisenox had the side effect, but all were successfully treated.
Trisenox also caused a heartbeat irregularity called an increased QT interval in 40 percent of patients. This irregularity can lead to arrhythmias, so the FDA urged that patients be closely monitored. Other side effects included nausea, vomiting, headache and fatigue.
Manufacturer Cell Therapeutics Inc. of Seattle said Trisenox will be available within three weeks, and a complete course of therapy will cost between $12,000 and $16,000.
Copyright 2000 The Associated Press. All rights reserved.