Conventional and high‐dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta‐analysis of 7258 patients

Abstract

Previous meta-analyses suggested that acute myeloid leukaemia induction regimens containing idarubicin (IDA) or high-dose daunorubicin (HDD) induce higher rates of complete remission (CR) than conventional-dose daunorubicin (CDD), with a possible benefit in overall survival. However, robust comparisons between these regimens are still lacking. We conducted a mixed treatment comparison meta-analysis regarding these three regimens. Mixed treatment comparison is a statistical method of data summarization that aggregates data from both direct and indirect effect estimates. Literature search strategy included MEDLINE, EMBASE, Cochrane, Scielo and LILACS, from inception until August 2013 and resulted in the inclusion of 17 trials enrolling 7258 adult patients. HDD [relative risk (RR) 1.13; 95% credible interval (CrI) 1.02-1.26] and IDA (RR 1.13; 95% CrI 1.05-1.23) showed higher CR rates than CDD. IDA also led to lower long-term overall mortality rates when compared with CDD (RR 0.93, 95% CrI 0.86-0.99), whereas HDD and CDD were no different (RR 0.94, 95% CrI 0.85-1.02). HDD and IDA comparison did not reach statistically significant differences in CR (RR 1.00; 95% CrI 0.89-1.11) and in long-term mortality (RR 1.01, 95% CrI 0.91-1.11). IDA and HDD are consistently superior to CDD in inducing CR, and IDA was associated with lower long-term mortality. On the basis of these findings, we recommend incorporation of IDA and HDD instead of the traditional CDD as standard treatments for acute myeloid leukaemia induction. The lack of HDD benefit on mortality, when compared with CDD in this study, should be cautiously addressed, because it may have been susceptible to underestimation because of statistical power limitations.

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

“…Metaanalyses of alternative anthracyclines did not suggest that there was a major difference between these agents. 12, 13 Several trials have tested cytosine arabinoside dose modification, again without convincing evidence of benefit. [14][15][16] Our previous trial in younger patients (Medical Research Council [MRC] AML15) demonstrated that the fludarabine/cytosine arabinoside/granulocyte colony-stimulating factor and idarubicin (FLAG-Ida) regimen can deliver a higher number of remissions with the first course and also reduce the risk of relapse.…”

Current treatment preferences in acute myeloid leukemia: a survey in Brazil

“…Moreover, daunorubicin is considered equivalent to idarubicin if the relative dose ratio (daunorubicin/idarubicin) is ≥5. 6 , 7 We found in this study that the most prescribed anthracycline was daunorubicin (60 mg/m 2 ), that is according to current practices.…”

A Bayesian Network Meta-Analysis Comparing the Efficacies of Eleven Novel Therapies with the Common Salvage Regimen for Relapsed or Refractory Acute Myeloid Leukemia

“…Other than the former relevant metaanalysis regarding the evaluation of routine treatments, we are the first to conduct an overall comparison among new selections using NMA, and this strategy and is expected to make a therapeutic breakthrough over traditional chemotherapies [29,30]. In the scope of these eleven interventions researched, some were indicative of significant efficacies when compared with the conventional salvage regimen.…”