Arsenic trioxide in patients with myelodysplastic syndromes: a phase II multicenter study.

Abstract

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 16 Pg. 2465-71 (Jun 01 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16651646 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Arsenicals
• Oxides
• Arsenic Trioxide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Arsenic Trioxide
• Arsenicals (administration & dosage, adverse effects, therapeutic use)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Hematologic Diseases (chemically induced)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy)
• Oxides (administration & dosage, adverse effects, therapeutic use)
• Prognosis
• Prospective Studies
• Risk Assessment
• Risk Factors
• Survival Analysis
• Treatment Outcome