Arsenic compounds in the treatment of multiple myeloma: a new role for a historical remedy.
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.
Berenson
James R
JR
Institute for Myeloma and Bone Cancer Research, West Hollywood, CA, USA. jberenson@imbcr.org
Yeh
Howard S
HS
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D049671:History, 18th Century; D006801:Humans; D008495:Medical Oncology / Q000266:history*; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy*; D010087:Oxides / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide