TY - JOUR
T1 - A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction
T2 - results from the UK NCRI AML17 trial in 1206 patients
AU - Burnett, Alan K
AU - Russell, Nigel H
AU - Hills, Robert K
AU - Kell, Jonathan
AU - Cavenagh, Jamie
AU - Kjeldsen, Lars
AU - McMullin, Mary-Frances
AU - Cahalin, Paul
AU - Dennis, Mike
AU - Friis, Lone
AU - Thomas, Ian F
AU - Milligan, Don
AU - Clark, Richard E
AU - UK NCRI AML Study Group
N1 - © 2015 by The American Society of Hematology.
PY - 2015/6/18
Y1 - 2015/6/18
N2 - Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been recommended as a standard of care. However, 60 mg/m(2) is widely used and has never been directly compared with 90 mg/m(2). As part of the UK National Cancer Research Institute (NCRI) AML17 trial, 1206 adults with untreated AML or high-risk myelodysplastic syndrome, mostly younger than 60 years of age, were randomized to a first-induction course of chemotherapy, which delivered either 90 mg/m(2) or 60 mg/m(2) on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m(2) on days 1, 3, and 5. There was no overall difference in complete remission rate (73% vs 75%; odds ratio, 1.07 [0.83-1.39]; P = .6) or in any recognized subgroup. The 60-day mortality was increased in the 90 mg/m(2) arm (10% vs 5% (hazard ratio [HR] 1.98 [1.30-3.02]; P = .001), which resulted in no difference in overall 2-year survival (59% vs 60%; HR, 1.16 [0.95-1.43]; P = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535.
AB - Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been recommended as a standard of care. However, 60 mg/m(2) is widely used and has never been directly compared with 90 mg/m(2). As part of the UK National Cancer Research Institute (NCRI) AML17 trial, 1206 adults with untreated AML or high-risk myelodysplastic syndrome, mostly younger than 60 years of age, were randomized to a first-induction course of chemotherapy, which delivered either 90 mg/m(2) or 60 mg/m(2) on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m(2) on days 1, 3, and 5. There was no overall difference in complete remission rate (73% vs 75%; odds ratio, 1.07 [0.83-1.39]; P = .6) or in any recognized subgroup. The 60-day mortality was increased in the 90 mg/m(2) arm (10% vs 5% (hazard ratio [HR] 1.98 [1.30-3.02]; P = .001), which resulted in no difference in overall 2-year survival (59% vs 60%; HR, 1.16 [0.95-1.43]; P = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535.
KW - Adolescent
KW - Adult
KW - Aged
KW - Antibiotics, Antineoplastic
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Cytarabine
KW - Daunorubicin
KW - Dose-Response Relationship, Drug
KW - Female
KW - Humans
KW - Induction Chemotherapy
KW - Kaplan-Meier Estimate
KW - Leukemia, Myeloid, Acute
KW - Male
KW - Middle Aged
KW - Young Adult
U2 - 10.1182/blood-2015-01-623447
DO - 10.1182/blood-2015-01-623447
M3 - Journal article
C2 - 25833957
SN - 0006-4971
VL - 125
SP - 3878
EP - 3885
JO - Blood
JF - Blood
IS - 25
ER -