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Blood, 15 January 2005, Vol. 105, No. 2, pp. 481-488. Prepublished online as a Blood First Edition Paper on June 22, 2004; DOI 10.1182/blood-2004-01-0326.
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS 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 cytarabineFrom the Department of Haematology, Westmead Hospital, Westmead, NSW, Australia; Statistical Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Royal Hobart Hospital, Hobart, TAS, Australia; Monash Medical Centre, Clayton, VIC, Australia; St George Hospital, Kogarah, NSW, Australia; Princess Alexandra Hospital, Woolloongabba, QLD, Australia; Wesley Medical Centre, Brisbane, QLD, Australia; Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Royal Perth Hospital, Perth, WA, Australia; Alfred Hospital, Prahran, VIC, Australia; Royal Brisbane Hospital, Herston, QLD, Australia; Mater Hospital, South Brisbane, QLD, Australia; Royal North Shore Hospital, St Leonards, NSW, Australia; Mater Hospital, Newcastle, NSW, Australia; Liverpool Hospital, Liverpool, NSW, Australia; Royal Melbourne Hospital, Melbourne VIC, Australia; and Fremantle Hospital, Fremantle, WA, Australia.
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.
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