Arsenic compounds have been used since ancient times to treat a wide variety of ailments. Although the use of
arsenic to treat hematologic
cancers has been documented since the 19th century, widespread use of
arsenic compounds in patients with
hematologic malignancies did not occur until the 1990s, when several groups in China reported impressive clinical response rates in patients with
acute promyelocytic leukemia who had received
arsenic trioxide. Subsequently, clinical studies conducted in the United States confirmed earlier reports, and
arsenic trioxide was approved by the Food and Drug Administration for the treatment of relapsed/refractory
acute promyelocytic leukemia. The use of
arsenic compounds in the treatment of
multiple myeloma (MM) is supported by the proposed mechanisms of action underlying the antitumor activity of
arsenic and by preclinical studies showing antiproliferative and cytotoxic activities in cell culture and animal models. Moreover, clinical studies of
arsenic compounds, particularly
arsenic trioxide-based regimens, have shown that this
drug is clinically active in patients with relapsed/refractory MM. Combination studies with other antimyeloma agents have shown evidence of synergy with
arsenic trioxide. Furthermore,
arsenic trioxide-based regimens in MM appear to be well tolerated, particularly with regard to
cardiac toxicity. The activity and tolerability observed in clinical studies promise to make
arsenic-based
chemotherapy a viable treatment option for patients whose disease does not respond to or who cannot tolerate other
chemotherapy regimens.