High-dose cytosine arabinoside in the treatment of acute myeloid leukemia: Review of three randomized trials.
BACKGROUND
The use of high-dose cytosine arabinoside (HDAraC) during induction may improve outcomes in patients with acute myeloid leukemia (AML) compared with standard-dose AraC (SDAraC). The objective of this review was to assess the impact of HDAraC during induction therapy for patients with AML based on results from randomized trials.


METHODS
All randomized trials in the field were identified by using a predefined search strategy. Trials that assessed the impact of HDAraC compared with SDAraC as induction therapy for adult patients with AML in a randomized fashion and that reported the relevant endpoints were included. Data were extracted from each trial by both reviewers according to prespecified criteria.


RESULTS
No differences between HDAraC and SDAraC were found with regard to complete remission rates (relative risk, 1.00; 95% confidence interval [95% CI], 0.92-1.10). The weighted mean difference (WMD) for median recurrence-free survival (RFS) was 4.19 in favor of HDAraC (95% CI, 0.59-7.78; P = .02). The WMD for 4-year RFS was 10.98 in favor of HDAraC (95% CI, 1.02-20.94; P = .03). The WMD for median overall survival (OS) was - 0.22 for HDAraC compared with SDAraC (95% CI, - 2.76-2.32; P = .9). Data regarding the median OS was heterogeneous between studies (chi-square P = .00), with 2 studies in favor of HDAraC and 2 studies in favor of SDAraC. The WMD for 4-year OS was 6.21 in favor of HDAraC (95% CI, 2.70-9.72; P = .0005).


CONCLUSIONS
Induction therapy with HDAraC improved long-term disease control and overall survival in adults age < 60 years with de novo AML. It remains unknown whether patients should receive HDAraC during induction or if it is to be given during postremission therapy. Further analyses should focus on this issue and on the effects of HDAraC in prognostically different subgroups of patients with AML.
Kern
Wolfgang
W
MLL Munich Leukemia Laboratory, Munich, Germany. wolfgang.kern@mll-online.com
Estey
Elihu H
EH
D000293:Adolescent; D000328:Adult; D003561:Cytarabine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
D003561:Cytarabine