Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study.
BACKGROUND
Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters.


METHODS
A total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 per course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks.


RESULTS
Patients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P < .001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate-2/high-risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment-naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]).


CONCLUSIONS
Decitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further.
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. hkantarj@mdanderson.org
Hagop
H
Kantarjian
Jean-Pierre J
JP
Issa
Craig S
CS
Rosenfeld
John M
JM
Bennett
Maher
M
Albitar
John
J
DiPersio
Virginia
V
Klimek
James
J
Slack
Carlos
C
de Castro
Farhad
F
Ravandi
Richard
R
Helmer
Lanlan
L
Shen
Stephen D
SD
Nimer
Richard
R
Leavitt
Azra
A
Raza
Hussain
H
Saba
D000208:Acute Disease; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality; D010166:Palliative Care; D011788:Quality of Life; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine