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

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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.

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