Arsenic for Acute Promyelocytic Leukemia Offers Complete Remission
Acute promyelocytic leukemia (APL) is a variant of acute myeloid leukemia that represents 10 percent to 15 percent of this cancer in adults. Since 1990, advances in treatment using all-trans-retinoic acid have more than doubled the survival rate in APL patients and cut the relapse rate of the 1980s by better than one-third (to about 20 percent).
Recent reports from China have suggested that intravenous infusions of the compound arsenic trioxide could lead to complete remissions in people with APL who have failed other forms of therapy. Spurred by these findings, researchers at Memorial Sloan-Kettering Cancer Center in New York attempted to determine arsenic trioxide's "mechanism of action," the molecular basics of how it works. The study's results, published in the Nov. 1998 issue of the New England Journal of Medicine, confirmed the preliminary reports from China, the authors said (see the journal abstract).
This study was not a trial comparing treatment types. The arsenic drug was given only to 12 APL patients who had multiple relapses despite extensive treatment with bone marrow transplant, retinoids (vitamin A derivatives), or conventional chemotherapy.
The study involved daily intravenous infusions with arsenic trioxide "until visible leukemic cells were removed from the bone marrow," the researchers reported.
Of the 12 patients studied, 11 had a complete remission after infusion treatments over a range of low daily doses. The median duration of remission was more than five months (remission ranged from one month to more than nine).
According to the authors, "[A]dverse effects were relatively mild and included rash, lightheadedness, fatigue, and musculoskeletal pain."
The researchers pointed out that despite "mild" side effects from the low study doses, the highest arsenic trioxide dose caused "a characteristic skin reaction to arsenic." This meant that increasing the dose beyond the range used in the study would probably cause severe toxic reactions, including possibly kidney failure.
As to arsenic trioxide's mechanism of action, the authors state it is too early to determine exactly. Preliminary findings indicate that the drug works against leukemic cells through an important cellular pathway involved in "apoptosis" -- programmed cell death. And it appears that all-trans-retinoic acid -- a retinoid compound that is often included with standard chemotherapy for APL -- also may work via this pathway, although the drugs clearly work by different mechanisms since arsenic was effective even in patients who had failed all-trans-retinoic acid.
In addition, another feature shared by these drugs is the rapid development of clinical resistance in some patients. The report concluded that arsenic trioxide "warrants further study" in APL and other cancers.
 Back to Top |
