Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer

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

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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 definitive conclusion. For Wilms' tumour, rhabdomyosarcoma/undifferentiated sarcoma, Ewing's sarcoma, and non-Hodgkin lymphoma 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 At the moment, there are 7 ongoing or unpublished randomised studies evaluating the use of anthracyclines in the following types of childhood cancer: hepatoblastoma/hepatocarcinoma, acute myeloid leukaemia (AML), ALL, rhabdomyosarcoma, and Wilms' tumour.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 1, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: van Dalen EC, Raphaël MF, Caron HN, Kremer LCM. Treatment including anthracyclines versus treatment not including anthracyclines for childhood cancer. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006647. DOI: 10.1002/14651858.CD006647.pub2.

This version first published online: January 21. 2009

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 different types of childhood cancer should be based on the available evidence on both antitumour efficacy and cardiotoxicity.

Objectives

To compare antitumour efficacy of treatment including or not including anthracyclines in children with childhood cancer.

Search strategy

We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, issue 4), MEDLINE (1966 to January 2007) and EMBASE (1980 to January 2007). 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 efficacy.

Data collection and analysis

Two reviewers independently performed the study selection, quality assessment and data-extraction.

Main results

We 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 studies had methodological limitations. For ALL no evidence of a significant difference in antitumour efficacy was identified in the meta-analyses, but in most individual studies there was a suggestion of better antitumour efficacy in patients treated with anthracyclines. For both Wilms' tumour 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 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.

Authors' conclusions

At 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.

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