Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer (Review)

van Dalen EC, Raphal MF, Caron HN, Kremer LCM

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 4 http://www.thecochranelibrary.com

Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

[Intervention Review]

Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer
Elvira C van Dalen1 , Martine F Raphal2 , Huib N Caron1 , Leontien CM Kremer1
1 Department of Paediatric Oncology, Emma Childrens Hospital / Academic Medical Center, Amsterdam, Netherlands. 2 Department of Pediatric Hematology and Oncology, Wilhelmina Childrens Hospital, University Medical Center Utrecht, Utrecht, Netherlands

Contact address: Elvira C van Dalen, Department of Paediatric Oncology, Emma Childrens Hospital / Academic Medical Center, PO Box 22660 (room TKsO-247), Amsterdam, 1100 DD, Netherlands. e.c.vandalen@amc.uva.nl. Editorial group: Cochrane Childhood Cancer Group. Publication status and date: Edited (no change to conclusions), published in Issue 4, 2012. Review content assessed as up-to-date: 1 September 2010. Citation: van Dalen EC, Raphal MF, Caron HN, Kremer LCM. Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD006647. DOI: 10.1002/14651858.CD006647.pub3. Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background One of the most important adverse effects of anthracyclines is cardiotoxicity. A well-informed decision on the use of anthracyclines in the treatment of childhood cancers should be based on evidence regarding both antitumour efcacy and cardiotoxicity. Objectives To compare antitumour efcacy of treatment including or not including anthracyclines in children with childhood cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 2), MEDLINE (1966 to March 2010) and EMBASE (1980 to March 2010). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trials databases. Selection criteria Randomised controlled trials (RCTs) comparing treatment of any type of childhood cancer with and without anthracyclines and reporting outcomes concerning antitumour efcacy. Data collection and analysis Two reviewers independently performed the study selection, risk of bias assessment and data extraction. Main results We identied RCTs for six types of tumour: acute lymphoblastic leukaemia (ALL) (three trials; 912 children), Wilms tumour (one trial; 316 children), rhabdomyosarcoma/undifferentiated sarcoma (one trial; 413 children), Ewings sarcoma (one trial; 94 children), nonHodgkin lymphoma (one trial; 284 children) and hepatoblastoma (one trial; 255 children). All studies had methodological limitations. For ALL no evidence of a signicant difference in antitumour efcacy was identied in the meta-analyses, but in most individual studies there was a suggestion of better antitumour efcacy in patients treated with anthracyclines. For both Wilms tumour and Ewings sarcoma a signicant difference in event-free and overall survival in favour of treatment with anthracyclines was identied,
Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

although for Wilms tumour the signicant difference in overall survival disappears with long-term follow-up. For rhabdomyosarcoma/ undifferentiated sarcoma, non-Hodgkin lymphoma and hepatoblastoma no difference in antitumour efcacy between the treatment groups was identied. Clinical cardiotoxicity was evaluated in three RCTs: no signicant difference between both treatment groups was identied, but in all individual studies there was a suggestion of a lower rate 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 identied. Authors conclusions At the moment no evidence from RCTs is available which underscores the use of anthracyclines in ALL. However, no evidence of effect, as identied in this review, is not the same as evidence of no effect. For Wilms tumour, rhabdomyosarcoma/undifferentiated sarcoma, Ewings sarcoma, non-Hodgkin lymphoma and hepatoblastoma only one RCT was available and, therefore, no denitive conclusions can be made about the antitumour efcacy of treatment with or without anthracyclines in these tumours. For other childhood cancers no RCTs were identied and therefore, no conclusions can be made about the antitumour efcacy of treatment with or without anthracyclines in these tumours.

PLAIN LANGUAGE SUMMARY Treatment with or without anthracycline chemotherapy for childhood cancer. Anthracyclines are used in the treatment of different types of childhood cancer. Unfortunately, one of the most important adverse effects of anthracyclines is damage to the heart. This can become manifest not only during treatment, but also years after the end of treatment. A well-informed decision on the use of anthracyclines in the treatment of different types of childhood cancer should be based on the available evidence on both antitumour effects of anthracyclines and the risk for damage to the heart. This systematic review focused on randomised studies evaluating the antitumour effects of anthracycline therapy. The authors found that at the moment no high quality evidence is available which shows that the use of anthracyclines has an increased antitumour effect in acute lymphoblastic leukaemia (ALL) as compared to treatment without anthracyclines, but there was some suggestion that this might be the case. Further high quality studies are needed to give a denitive conclusion. For Wilms tumour, rhabdomyosarcoma/ undifferentiated sarcoma, Ewings sarcoma, non-Hodgkin lymphoma and hepatoblastoma the reviewers found only limited data and were unable to draw conclusions. Also, there are no data for other childhood cancers. More high quality research is needed. At the moment, there are six ongoing or unpublished randomised studies evaluating the use of anthracyclines in the following types of childhood cancer: hepatoblastoma, acute myeloid leukaemia (AML), ALL, rhabdomyosarcoma, and Wilms tumour.

Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.