title: A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients.
abstract: 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.
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.affiliation: Department of Haematology, Nottingham University Hospital NHS Trust, Nottingham, United Kingdom;
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.affiliation: Department of Haematology, University Hospital of Wales Cardiff, United Kingdom;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kell
authors.affiliation: Department of Haematology, St Bartholomew's Hospital, West Smithfield, London United Kingdom;
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark;
authors.forename: Lars
authors.initials: L
authors.lastname: Kjeldsen
authors.affiliation: Department of Haematology, Belfast City Hospital, Belfast, United Kingdom;
authors.forename: Mary-Frances
authors.initials: MF
authors.lastname: McMullin
authors.affiliation: Blackpool Victoria Hospital, Blackpool, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Cahalin
authors.affiliation: Department of Haematology, Christie Hospital, Manchester, United Kingdom;
authors.forename: Mike
authors.initials: M
authors.lastname: Dennis
authors.affiliation: Department of Haematology, University of Odense, Odense, Denmark;
authors.forename: Lone
authors.initials: L
authors.lastname: Friis
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;
authors.forename: Ian F
authors.initials: IF
authors.lastname: Thomas
authors.affiliation: Department of Haematology, Heartlands Hospital, Birmingham, United Kingdom; and.
authors.forename: Don
authors.initials: D
authors.lastname: Milligan
authors.affiliation: Department of Haematology, Royal Liverpool University Hospital, Liverpool, United Kingdom.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D003561:Cytarabine; D003630:Daunorubicin
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