Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia.
OBJECTIVE
This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics.


METHODS
Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m(2) per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m(2) per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded.


RESULTS
The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%).


CONCLUSIONS
In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis.
Department of Leukemia, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. hkantarj@mdanderson.org
Hagop M
HM
Kantarjian
Xavier G
XG
Thomas
Anna
A
Dmoszynska
Agnieszka
A
Wierzbowska
Grzegorz
G
Mazur
Jiri
J
Mayer
Jyh-Pyng
JP
Gau
Wen-Chien
WC
Chou
Rena
R
Buckstein
Jaroslav
J
Cermak
Ching-Yuan
CY
Kuo
Albert
A
Oriol
Farhad
F
Ravandi
Stefan
S
Faderl
Jacques
J
Delaunay
Daniel
D
Lysák
Mark
M
Minden
Christopher
C
Arthur
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002755:Choice Behavior; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003657:Decision Making; D000077209:Decitabine; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D010166:Palliative Care / Q000379:methods; D010358:Patient Participation; D012074:Remission Induction; D018570:Risk Assessment; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D000077209:Decitabine; D001374:Azacitidine