A new report has raised questions about the safety of arsenic trioxide, a compound recently approved in the United States for treating acute promyelocytic leukaemia, a rare subtype of acute myelogenous leukaemia.
In a study of 10 patients who had leukaemia that had relapsed or had not responded to conventional treatment and who were taking arsenic trioxide, three died suddenly, researchers reported (Blood 2001;98:266-71).
Even though the compound may provide benefits to some patients with leukaemia, "arsenic trioxide may be significantly, perhaps fatally, toxic at doses currently in use," reported the team of researchers, led by Dr Peter Westervelt of the University of Massachusetts Medical School in Worcester.
The standard treatment for acute promyelocytic leukaemia, all-trans retinoic acid, a vitamin A derivative, has a high success rate. But some patients either do not respond to the treatment or experience a relapse of the disease.
Last September, after a US study found that most patients also treated with arsenic trioxide went into complete remission, the US Food and Drug Administration (FDA) approved the drug to treat patients with this form of leukaemia. The latest study was conducted with a form of the drug that is different from Trisenox, the version approved last September by the FDA.
The causes of death are uncertain, as postmortem examinations conducted on two of the patients were inconclusive. But the researchers said that it was possible the deaths were related to the treatment, particularly as arsenic has previously been shown to trigger dangerous abnormalities in heart rhythm, including prolonged QT interval and ventricular premature contractions (Annals of Internal Medicine 2000;133:881-5).
In previous studies of patients with acute promyelocytic leukaemia, arsenic trioxide showed good safety. "Over 500 patients have been treated with the FDA-approved product with no sudden deaths," said a statement from Cell Therapeutics, the company that markets Trisenox. "This is a potential life-saving therapy . . . and when monitored correctly provides them an opportunity to get rid of their leukemia while preserving their quality of life."
Dr Westervelt and his colleagues suggested that variations in the current formulation of arsenic trioxide may account for the potential toxicity. "Our observations should nonetheless raise a cautionary flag to practitioners regarding the potential for previously under-appreciated cardiac toxicity with this agent," Dr Westervelt and his colleagues said in a statement.
"We await data from studies currently being conducted by the FDA to determine whether formulation issues might account for the toxicity differences," the statement said.