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A randomized study of high-dose cytarabine in induction in acute myeloid
leukemia [see comments]
JF Bishop, JP Matthews, GA Young, J Szer, A Gillett, D Joshua, K Bradstock, A Enno, MM Wolf and R Fox
Australian Leukemia Study Group, Peter MacCallum Cancer Institute,
Melbourne, Australia.
High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic
blasts. It has been used as a successful salvage and in postremission
therapy but not as initial induction treatment. Patients aged 15 to 60
years, presenting with newly diagnosed acute myeloid leukemia (AML) were
randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days
1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75
mg/m2 days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m2
continuous intravenous infusion for 7 days with daunorubicin and etoposide
at the same dose and schedule as above (7-3-7). Patients could receive a
second or third induction course if complete remission (CR) was not
achieved. All patients received the same postinduction consolidation
therapy (5-2-5) for 2 courses. Eligible patients had no prior chemotherapy
or myelodysplastic disease. Patients have been followed for a median of 4.5
years. Of 301 patients treated, complete response (CR) was achieved in 71%
with HIDAC- 3-7 and 74% with 7-3-7. For patients in CR, the estimated
median remission duration was 45 months with HIDAC-3-7 and 12 months with
7-3- 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis).
The estimated percentage of patients relapse free 5 years after achieving a
CR was 49% on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive
longer with HIDAC-3-7 but there were no overall survival differences
between the two arms. HIDAC-3-7 was associated with significantly more
toxicity in induction with more leukopenia, thrombocytopenia, nausea, and
vomiting and eye toxicity (all P < .001) but a similar incidence of
severe central nervous system and cerebellar toxicity compared to 7-3-7.
The consolidation treatment was the same in both arms but caused
significantly more leukopenia and thrombocytopenia in patients previously
treated with HIDAC-3-7 induction (P < .0001). We conclude that a
dose-effect exists for cytarabine in AML and that HIDAC- 3-7 prolongs
remission duration and disease-free survival and is tolerable when used as
initial induction therapy in patients with de novo AML.
Volume 87,
Issue 5,
pp. 1710-1717,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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