This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Douer, D. Articles by Tallman, M. S. Search for Related Content PubMed PubMed Citation Articles by Douer, D. Articles by Tallman, M. S. Social Bookmarking                            What's this?

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				L. C. Platanias Biological Responses to Arsenic Compounds J. Biol. Chem., July 10, 2009; 284(28): 18583 - 18587. [Abstract] [Full Text] [PDF]

				S. Ying, K. Myers, S. Bottomley, T. Helleday, and H. E. Bryant BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells Nucleic Acids Res., June 23, 2009; (2009) gkp538v1. [Abstract] [Full Text] [PDF]

				A. Sassano, M. Lo Iacono, G. Antico, A. Jordan, S. Uddin, R. A. Calogero, and L. C. Platanias Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins Mol. Cancer Ther., March 1, 2009; 8(3): 615 - 625. [Abstract] [Full Text] [PDF]

				M. A. Sanz, D. Grimwade, M. S. Tallman, B. Lowenberg, P. Fenaux, E. H. Estey, T. Naoe, E. Lengfelder, T. Buchner, H. Dohner, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet Blood, February 26, 2009; 113(9): 1875 - 1891. [Abstract] [Full Text] [PDF]

				Y. MOLIN, P. FRISK, and N.-G. ILBACK Arsenic Trioxide Affects the Trace Element Balance in Tissues in Infected and Healthy Mice Differently Anticancer Res, January 1, 2009; 29(1): 83 - 90. [Abstract] [Full Text] [PDF]

				A. Yoda, K. Toyoshima, Y. Watanabe, N. Onishi, Y. Hazaka, Y. Tsukuda, J. Tsukada, T. Kondo, Y. Tanaka, and Y. Minami Arsenic Trioxide Augments Chk2/p53-mediated Apoptosis by Inhibiting Oncogenic Wip1 Phosphatase J. Biol. Chem., July 4, 2008; 283(27): 18969 - 18979. [Abstract] [Full Text] [PDF]

				B. Dolniak, E. Katsoulidis, N. Carayol, J. K. Altman, A. J. Redig, M. S. Tallman, T. Ueda, R. Watanabe-Fukunaga, R. Fukunaga, and L. C. Platanias Regulation of Arsenic Trioxide-induced Cellular Responses by Mnk1 and Mnk2 J. Biol. Chem., May 2, 2008; 283(18): 12034 - 12042. [Abstract] [Full Text] [PDF]

				J. K. Altman, P. Yoon, E. Katsoulidis, B. Kroczynska, A. Sassano, A. J. Redig, H. Glaser, A. Jordan, M. S. Tallman, N. Hay, et al. Regulatory Effects of Mammalian Target of Rapamycin-mediated Signals in the Generation of Arsenic Trioxide Responses J. Biol. Chem., January 25, 2008; 283(4): 1992 - 2001. [Abstract] [Full Text] [PDF]

				E. H. Kim, M. J. Yoon, S. U. Kim, T. K. Kwon, S. Sohn, and K. S. Choi Arsenic Trioxide Sensitizes Human Glioma Cells, but not Normal Astrocytes, to TRAIL-Induced Apoptosis via CCAAT/Enhancer-Binding Protein Homologous Protein Dependent DR5 Up-regulation Cancer Res., January 1, 2008; 68(1): 266 - 275. [Abstract] [Full Text] [PDF]

				S. M. Kelly, J. K. VanSlyke, and L. S. Musil Regulation of Ubiquitin-Proteasome System mediated Degradation by Cytosolic Stress Mol. Biol. Cell, November 1, 2007; 18(11): 4279 - 4291. [Abstract] [Full Text] [PDF]

				J. Lu, E.-H. Chew, and A. Holmgren Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide PNAS, July 24, 2007; 104(30): 12288 - 12293. [Abstract] [Full Text] [PDF]

				V. Mathews, M. Thomas, V. M Srivastava, B. George, A. Srivastava, and M. Chandy Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen Haematologica, July 1, 2007; 92(7): 994 - 995. [Abstract] [Full Text] [PDF]

				S. Kitareewan, B. D. Roebuck, E. Demidenko, R. D. Sloboda, and E. Dmitrovsky Lysosomes and Trivalent Arsenic Treatment in Acute Promyelocytic Leukemia J Natl Cancer Inst, January 3, 2007; 99(1): 41 - 52. [Abstract] [Full Text] [PDF]

				P. Yoon, N. Giafis, J. Smith, H. Mears, E. Katsoulidis, A. Sassano, J. Altman, A. J. Redig, M. S. Tallman, and L. C. Platanias Activation of mammalian target of rapamycin and the p70 S6 kinase by arsenic trioxide in BCR-ABL-expressing cells. Mol. Cancer Ther., November 1, 2006; 5(11): 2815 - 2823. [Abstract] [Full Text] [PDF]

				P. Kannan-Thulasiraman, E. Katsoulidis, M. S. Tallman, J. S. C. Arthur, and L. C. Platanias Activation of the Mitogen- and Stress-activated Kinase 1 by Arsenic Trioxide J. Biol. Chem., August 11, 2006; 281(32): 22446 - 22452. [Abstract] [Full Text] [PDF]

				A. Navas-Acien, A. R. Sharrett, and E. Guallar THREE AUTHORS REPLY Am. J. Epidemiol., July 15, 2006; 164(2): 195 - 196. [Full Text] [PDF]

				D. Douer ATO: the forefront of APL treatment? Blood, April 1, 2006; 107(7): 2588 - 2589. [Full Text] [PDF]

				V. Mathews, B. George, K. M. Lakshmi, A. Viswabandya, A. Bajel, P. Balasubramanian, R. V. Shaji, V. M. Srivastava, A. Srivastava, and M. Chandy Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity Blood, April 1, 2006; 107(7): 2627 - 2632. [Abstract] [Full Text] [PDF]

				M. A. Sanz Treatment of Acute Promyelocytic Leukemia Hematology, January 1, 2006; 2006(1): 147 - 155. [Abstract] [Full Text] [PDF]

				F. Lo-Coco and E. Ammatuna The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment Hematology, January 1, 2006; 2006(1): 156 - 161. [Abstract] [Full Text] [PDF]

				R. E. Gale, R. Hills, A. R. Pizzey, P. D. Kottaridis, D. Swirsky, A. F. Gilkes, E. Nugent, K. I. Mills, K. Wheatley, E. Solomon, et al. Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia Blood, December 1, 2005; 106(12): 3768 - 3776. [Abstract] [Full Text] [PDF]