Originally published as JCO Early Release 10.1200/JCO.2005.03.9503 on May 1 2006

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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, Pierre Fenaux

From the Institut Paoli-Calmettes, Marseille; Groupe Français des Myélodysplasies, Paris; CHU Nancy Brabois, Vandoeuvre-Les Nancy; Universite Paris 7 –Denis Diderot; Hopital Cochin; Hopital Hotel Dieu, Paris; Institut Gustave Roussy, Villejuif; CHU de Nice-Hopital de l'Archet 1, Nice; Hopital Beaujon, Clichy, France; Cliniques Universitaires de Mont-Godinne, Yvoir; Hopital Erasme, Bruxelles, Belgium; Ninewells Hospital, Dundee; University Hospital of Wales, Cardiff; Christie Hospital NHS Trust, Manchester, United Kingdom

Address reprint requests to Norbert Vey, MD, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, 13009 Marseille, France; e-mail: veyn{at}marseille.fnclcc.fr

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

PATIENTS AND METHODS: MDS patients diagnosed according to standard French-American-British criteria received a loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks. Patients were divided into two cohorts: lower-risk MDS (International Prognostic Scoring System risk category low or intermediate 1) and higher-risk MDS (International Prognostic Scoring System risk category intermediate 2 or high). Modified International Working Group criteria were used for response evaluation.

RESULTS: Of 115 patients enrolled and treated in the study, 67% of patients were transfusion dependent at baseline; median age was 68 years. Most treatment-related adverse events were mild to moderate. The overall rate of hematologic improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one partial response in the higher-risk cohort. The hematologic response rates were 13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk MDS, respectively. Major responses were observed in all three hematologic lineages; 16% of RBC transfusion-dependent patients and 29% of platelet transfusion-dependent patients became transfusion independent. At data cut off, the median response duration was 3.4 months, with responses ongoing in nine patients.

CONCLUSION: Arsenic trioxide treatment consisting of an initial loading dose followed by maintenance therapy has moderate activity in MDS, inducing hematologic responses in both lower- and higher-risk patients. This activity combined with a manageable adverse effect profile warrants the additional study of arsenic trioxide, particularly in combination therapy, for the treatment of patients with MDS.

Supported by Cell Therapeutics Inc, Seattle, WA.

Preliminary results of this study were presented at the 46th Annual Meeting of American Society of Hematology, San Diego, CA, December 4-7, 2004.

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

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