The efficacy and safety of daunorubicin versus idarubicin combined with cytarabine for induction therapy in acute myeloid leukemia: A meta-analysis of randomized clinical trials

• Published in: Medicine (Baltimore) Vol. 99; no. 24; p. e20094
• Main Authors: Wang, Hanyu, Xiao, Xueting, Xiao, Qirong, Lu, Yanhong, Wu, Yong
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 12.06.2020
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cytarabine - adverse effects; Cytarabine - therapeutic use; Daunorubicin - adverse effects; Daunorubicin - therapeutic use; Female; Humans; Idarubicin - adverse effects; Idarubicin - therapeutic use; Induction Chemotherapy - methods; Leukemia, Myeloid, Acute - drug therapy; Male; Middle Aged; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Safety; Survival Analysis; Systematic Review and Meta-Analysis; Topoisomerase II Inhibitors - adverse effects; Topoisomerase II Inhibitors - therapeutic use; Treatment Outcome; United States - epidemiology; Young Adult; United States
• ISSN: 0025-7974; 1536-5964
• DOI: 10.1097/MD.0000000000020094

To ascertain the efficacy and safety of daunorubicin combined with cytarabine comparing with idarubicin combined with cytarabine as a standard induction therapy for acute Myeloid leukemia by a meta-analysis. The randomized controlled trials included were retrieved from PubMed, Embase, and Cochrane library. We evaluated and cross-checked the randomized clinical trials (RCTs) comparing daunorubicin combined with cytarabine (DA) and idarubicin combined with cytarabine (IA) by two reviewers independently according to Cochrane Handbook for Systematic Reviewers of Interventions. The data of meta-analysis was conducted using Review Manager 5.3 and Stata 12.0 software. A total of 6 studies containing 3140 patients were included. The primary outcomes were complete remission (CR), CR in one course (CR1), CR in two courses (CR2), overall survival (OS), and relapse rate. The secondary outcomes included adverse events and cytogenetic risk in subgroup analyses. IA showed a statistically significant in CR (RR = 1.05; 95%CI = 1.00-1.09, P = .03) and CR1 (RR = 1.11; 95%CI = 1.04-1.18, P = .003), but not in CR2 (RR = 0.97; 95%CI = 0.77-1.24, P = .83), and relapse rate (RR = 1.08; 95%CI = 0.98-1.43, P = .08). In high dose daunorubicin group, OS was significantly improved with IA compared to DA (HR = 0.89, 95%CI = 0.8-1.0, P = .041, I = 0). At grade 3/4 adverse events, the difference between IA and DA was not statistically significant (infection, P = .28; cardiac toxicity, P = .15; bleeding, P = .29). In the subgroup analysis, the genotypes of the IA and DA groups were not statistically significant for comparison of CR between the two groups (P = .07). This meta-analysis showed that IA had a better efficacy in the treatment of acute myeloid leukemia than DA, even with increased doses of DA. The OS of a standard dose of IA patients was longer than that of DA patients. Our research shows that anthracycline dose intensification of daunorubicin is of no clinically relevant benefit in AML patients comparing with a standard dose of IA. When it comes to adverse drug reactions, it is not a significant difference. Therefore, in clinical practice, IA should be the first choice for induction regimen in patients with acute myeloid leukemia.