In addition, we searched reference

lists of relevant articles, conference proceedings and ongoing trials databases.\n\nSelection criteria\n\nRandomised controlled trials (RCTs) comparing treatment of any type of childhood cancer with and without anthracyclines and reporting outcomes concerning antitumour efficacy.\n\nData collection and analysis\n\nTwo reviewers independently performed the study selection, quality assessment and data-extraction.\n\nMain results\n\nWe identified RCTs for 5 types of tumour: acute lymphoblastic leukaemia (ALL) (n=3; 912 children), Wilms’ tumour (n=1; 316 children), rhabdomyosarcoma/undifferentiated sarcoma (n= 1; 413 children), Ewing’s sarcoma (n=1; 94 children), and non-Hodgkin lymphoma (n= 1; 284 children). All GSK2399872A studies had methodological limitations. For ALL no evidence of a significant difference in antitumour efficacy was identified in the meta-analyses, but inmost individual studies there was a suggestion

of better antitumour efficacy in patients treated with anthracyclines. For both Wilms’ tumour BAY 73-4506 and Ewing’s sarcoma a significant difference in survival in favour of treatment with anthracyclines was identified. The hazard ratios for overall and event-free survival in Wilms’ tumour were 1.85 (95% CI 1.09 to 3.15) and 2.21 (95% CI 1.44 to 3.40), respectively. For patients with Ewing’s sarcoma only descriptive results were available (P = 0.02 for overall survival and P = 0.01 for event-free survival). For both rhabdomyosarcoma/undifferentiated sarcoma and non-Hodgkin lymphoma no difference in antitumour efficacy between the treatment groups was identified. Clinical

cardiotoxicity was evaluated in 3 RCTs. No significant difference between both treatment groups was identified, but in all individual studies there was a suggestion of a lower rate Pexidartinib concentration of clinical cardiotoxicity in patients who did not receive anthracyclines. None of the studies evaluated asymptomatic cardiac dysfunction. For other childhood cancers no RCTs were identified.\n\nAuthors’ conclusions\n\nAt the moment no evidence from RCTs is available which underscores the use of anthracyclines in ALL. However, it should be noted that “no evidence of effect”, as identified in this review, is not the same as “evidence of no effect”. For Wilms’ tumour, rhabdomyosarcoma/undifferentiated sarcoma, Ewing’s sarcoma, and non-Hodgkin lymphoma only 1 RCT was available and therefore, no definitive conclusions can be made about the antitumour efficacy of treatment with or without anthracyclines in these tumours. For other childhood cancers no RCTs were identified and therefore, no conclusions can be made about the antitumour efficacy of treatment with or without anthracyclines in these tumours. More high quality research is needed.