title: A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine.
abstract: The value of administering sequential courses of chemotherapy containing high-dose cytarabine in both induction and consolidation therapy for acute myeloid leukemia (AML) has not been assessed in a prospective randomized trial. Two hundred ninety-two AML patients aged 15 to 60 years were enrolled in the Australasian Leukaemia and Lymphoma Group (ALLG) AML trial number 7 (M7) protocol to evaluate this question. All received induction therapy with the ICE protocol (idarubicin 9 mg/m2 x 3; cytarabine 3 g/m2 twice a day on days 1, 3, 5, 7; etoposide 75 mg/m2 x 7). Complete remission was achieved in 234 (80%) patients. Two hundred two patients in remission were then randomized to either a further identical cycle of ICE or 2 attenuated courses (cytarabine 100 mg/m2 daily x 5, idarubicin x 2, etoposide x 5 [IcE]). ICE consolidation therapy was more toxic than IcE, however, the treatment-related death rate was not significantly different. There was no difference between the 2 consolidation arms for relapse-free survival at 3 years (49% for ICE vs 46% for IcE; P = .66), survival following randomization (61% vs 62%; P = .91), or the cumulative incidence of relapse (43% vs 51%; P = .31), and there was no difference within cytogenetic risk groups. Intensive induction chemotherapy incorporating high-dose cytarabine results in high complete remission rates, but further intensive consolidation treatment does not appear to confer additional benefit.
authors.affiliation: Department of Haematology, Westmead Hospital, Westmead, NSW, Australia. bradstok@icpmr.wsahs.nsw.gov.au
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bradstock
authors.forename: Jane P
authors.initials: JP
authors.lastname: Matthews
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Lowenthal
authors.forename: Heather
authors.initials: H
authors.lastname: Baxter
authors.forename: John
authors.initials: J
authors.lastname: Catalano
authors.forename: Timothy
authors.initials: T
authors.lastname: Brighton
authors.forename: Devinder
authors.initials: D
authors.lastname: Gill
authors.forename: Paul
authors.initials: P
authors.lastname: Eliadis
authors.forename: Douglas
authors.initials: D
authors.lastname: Joshua
authors.forename: Paul
authors.initials: P
authors.lastname: Cannell
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: Simon
authors.initials: S
authors.lastname: Durrant
authors.forename: Anne
authors.initials: A
authors.lastname: Gillett
authors.forename: Jerry
authors.initials: J
authors.lastname: Koutts
authors.forename: Kerry
authors.initials: K
authors.lastname: Taylor
authors.forename: John
authors.initials: J
authors.lastname: Bashford
authors.forename: Christopher
authors.initials: C
authors.lastname: Arthur
authors.forename: Arno
authors.initials: A
authors.lastname: Enno
authors.forename: Lindsay
authors.initials: L
authors.lastname: Dunlop
authors.forename: Jeff
authors.initials: J
authors.lastname: Szer
authors.forename: Michael
authors.initials: M
authors.lastname: Leahy
authors.forename: Surender
authors.initials: S
authors.lastname: Juneja
authors.forename: Graham A R
authors.initials: GA
authors.lastname: Young
mesh_terms: D000208:Acute Disease; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / 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; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003561:Cytarabine; D005047:Etoposide; D015255:Idarubicin