Arsenic trioxide in patients with myelodysplastic syndromes: a phase II multicenter study.
OBJECTIVE
Evaluation of the safety and efficacy of arsenic trioxide in patients with myelodysplastic syndromes (MDS).


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.


CONCLUSIONS
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.
Vey
Norbert
N
Institut Paoli-Calmettes, Marseille, France. veyn@marseille.fnclcc.fr
Bosly
Andre
A
Guerci
Agnes
A
Feremans
Walter
W
Dombret
Herve
H
Dreyfus
Francois
F
Bowen
David
D
Burnett
Alan
A
Dennis
Mike
M
Ribrag
Vincent
V
Casadevall
Nicole
N
Legros
Laurence
L
Fenaux
Pierre
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide