Originally published as JCO Early Release 10.1200/JCO.2005.03.7903 on May 1 2006

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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schiller, G. J. Articles by List, A. F. Search for Related Content PubMed PubMed Citation Articles by Schiller, G. J. Articles by List, A. F. Related Articles Related Article Related Editorial

Phase II Multicenter Study of Arsenic Trioxide in Patients With Myelodysplastic Syndromes

Gary J. Schiller, James Slack, John D. Hainsworth, James Mason, Mansoor Saleh, David Rizzieri, Dan Douer, Alan F. List

From the UCLA Division of Hematology-Oncology, University of California Los Angeles; Norris Cancer Center, University of Southern California School of Medicine, Los Angeles; Scripps Cancer Center, San Diego, CA; Mayo Clinic, Scottsdale, AZ; Sarah Cannon Cancer Center, Nashville, TN; Georgia Cancer Specialists, Tucker, GA; Duke University Medical Center, Durham, NC; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

Address reprint requests to Gary J. Schiller, MD, UCLA Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA 90095; e-mail: garyjs{at}ucla.edu

PURPOSE: To evaluate the efficacy and safety of arsenic trioxide monotherapy in patients with myelodysplastic syndromes (MDS).

PATIENTS AND METHODS: Patients received arsenic trioxide (0.25 mg/kg/d) on 5 consecutive days per week for 2 weeks, followed by 2 weeks’ rest (one cycle). Two patient cohorts were established according to International Prognostic Scoring System risk category: lower-risk (low or intermediate-1) or higher-risk MDS (intermediate-2 or high). For lower-risk MDS, hematologic improvement (HI) was the primary response end point. For higher-risk MDS, additional end points included complete or partial remission. Based on the expected time to response, patients receiving two or more cycles were prospectively evaluated.

RESULTS: Hematologic adverse events included neutropenia, thrombocytopenia, and febrile neutropenia. Two patients died during the study due to treatment-related toxicities. Most common grade 3/4 nonhematologic events were pneumonia, fatigue, hemorrhage, pain, and dyspnea. Among patients who received one or more doses (n = 70) or completed two or more cycles (n = 51), the HI rates were 34% and 39% in lower-risk patients, and 6% and 9% in higher-risk patients, respectively; the overall major HI rates were 20% and 22%. One higher-risk patient achieved a complete remission (3%). Major HIs were observed in all hematologic lineages; erythroid responses were the most common. Transfusion independence or reduction by 50% occurred in 33% of patients dependent on RBC transfusions. The overall median duration of HI was 6.8 months (range, 2 to 40 months).

CONCLUSION: Arsenic trioxide monotherapy has moderate activity against MDS, with a manageable adverse effect profile. The further study of arsenic trioxide in MDS, particularly in combination with other agents, is warranted.

Supported by Cell Therapeutics Inc, Seattle, WA.

Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

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

Related Article

• Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study
  Norbert Vey, Andre Bosly, Agnes Guerci, Walter Feremans, Herve Dombret, Francois Dreyfus, David Bowen, Alan Burnett, Mike Dennis, Vincent Ribrag, Nicole Casadevall, Laurence Legros, and Pierre Fenaux
  JCO 2006 24: 2465-2471 [Abstract] [Full Text]

Related Editorial

• Is Intravenous Arsenic Trioxide a Useful Therapy in Myelodysplastic Syndromes?
  Richard M. Stone
  JCO 2006 24: 2414-2416 [Full Text]

This article has been cited by other articles:

				V. G. Sankaran, S. H. Orkin,, and C. R. Walkley Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis Genes & Dev., February 15, 2008; 22(4): 463 - 475. [Abstract] [Full Text] [PDF]

				D. Shackelford, C. Kenific, A. Blusztajn, S. Waxman, and R. Ren Targeted Degradation of the AML1/MDS1/EVI1 Oncoprotein by Arsenic Trioxide Cancer Res., December 1, 2006; 66(23): 11360 - 11369. [Abstract] [Full Text] [PDF]

				D. CILLONI, E. MESSA, F. MESSA, S. CARTURAN, I. DEFILIPPI, F. ARRUGA, V. ROSSO, R. CATALANO, E. BRACCO, P. NICOLI, et al. Genetic Abnormalities as Targets for Molecular Therapies in Myelodysplastic Syndromes Ann. N.Y. Acad. Sci., November 1, 2006; 1089(1): 411 - 423. [Abstract] [Full Text] [PDF]

				N. Vey, A. Bosly, A. Guerci, W. Feremans, H. Dombret, F. Dreyfus, D. Bowen, A. Burnett, M. Dennis, V. Ribrag, et al. Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study J. Clin. Oncol., June 1, 2006; 24(16): 2465 - 2471. [Abstract] [Full Text] [PDF]

				R. M. Stone Is Intravenous Arsenic Trioxide a Useful Therapy in Myelodysplastic Syndromes? J. Clin. Oncol., June 1, 2006; 24(16): 2414 - 2416. [Full Text] [PDF]