title: 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.
authors.affiliation: Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Institute for Research and Education, Hospital Moinhos de Vento, Porto Alegre, Brazil.
authors.forename: Leo
authors.initials: L
authors.lastname: Sekine
authors.affiliation: Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Vinícius Daudt
authors.initials: VD
authors.lastname: Morais
authors.affiliation: Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Institute for Research and Education, Hospital Moinhos de Vento, Porto Alegre, Brazil.
authors.forename: Karine Margarites
authors.initials: KM
authors.lastname: Lima
authors.affiliation: Internal Medicine Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Tor Gunnar Hugo
authors.initials: TG
authors.lastname: Onsten
authors.affiliation: Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|Statistics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|National Institute of Science and Technology for Health Technology Assessment, CNPq, Porto Alegre, Brazil.
authors.forename: Patrícia Klarmann
authors.initials: PK
authors.lastname: Ziegelmann
authors.affiliation: Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.|National Institute of Science and Technology for Health Technology Assessment, CNPq, Porto Alegre, Brazil.|Institute for Research and Education, Hospital Moinhos de Vento, Porto Alegre, Brazil.
authors.forename: Rodrigo Antonini
authors.initials: RA
authors.lastname: Ribeiro
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D012074:Remission Induction
chemical_list: D015255:Idarubicin; D003630:Daunorubicin
keywords: acute myeloid leukaemia; anthracyclines; daunorubicin; idarubicin; induction chemotherapy; remission induction