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Arsenic Trioxide: New Clinical Experience With an Old Medication in Hematologic Malignancies

From the Division of Hematology, Norris Comprehensive Cancer Center and Hospital, University of Southern California at Los Angeles, Keck School of Medicine, Los Angeles, CA; and Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.

Address reprint requests to Dan Douer, MD, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Rm 3460, Los Angeles, CA 90033; e-mail: douer_d{at}ccnt.hsc.usc.edu

Arsenic trioxide has shown great promise in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APL). In clinical trials, arsenic trioxide induces complete remission in 87% of patients and molecular remission in 83% of patients. Two-year overall and relapse-free survival estimates are 63% and 49%, respectively. Treatment with arsenic trioxide may be associated with the APL differentiation syndrome, leukocytosis, and electrocardiographic abnormalities. The expanded use of arsenic trioxide in APL for postremission therapy, in conjunction with transplantation, and in patients with newly diagnosed APL is under investigation. The multiple mechanisms of action of arsenic trioxide suggest that it may have antitumor activity in malignancies other than APL and that it may be used in combination with other agents to expand its potential use. This article reviews the clinical use of arsenic trioxide to date and discusses new therapeutic strategies evolving from its diverse biologic activities.

Supported by the Orange County Education and Research Foundation.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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