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Open Access Highly Accessed Research article

Cardiotoxicity of anthracycline agents for the treatment of cancer: Systematic review and meta-analysis of randomised controlled trials

Lesley A Smith1*, Victoria R Cornelius1, Christopher J Plummer2, Gill Levitt3, Mark Verrill4, Peter Canney5 and Alison Jones6

Author Affiliations

1 Medical Research Matters, 77 Witney Road, Eynsham, OX29 4PN, UK

2 Department of Cardiology, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK

3 Great Ormond St Hospital for Sick Children NHS Trust, London, WCIN3JH, UK

4 Northern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, UK

5 Beatson West of Scotland Cancer Centre, Gartnavel General Hospital, Great Western Road, Glasgow, G12 0NY, UK

6 UCLH Foundation Trust, Cancer Management, 3rd Floor West, 250 Euston Road, London NW1 2PG, UK

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BMC Cancer 2010, 10:337  doi:10.1186/1471-2407-10-337

Published: 29 June 2010

Abstract

Background

We conducted a systematic review and meta-analysis to clarify the risk of early and late cardiotoxicity of anthracycline agents in patients treated for breast or ovarian cancer, lymphoma, myeloma or sarcoma.

Methods

Randomized controlled trials were sought using comprehensive searches of electronic databases in June 2008. Reference lists of retrieved articles were also scanned for additional articles. Outcomes investigated were early or late clinical and sub-clinical cardiotoxicity. Trial quality was assessed, and data were pooled through meta-analysis where appropriate.

Results

Fifty-five published RCTs were included; the majority were on women with advanced breast cancer. A significantly greater risk of clinical cardiotoxicity was found with anthracycline compared with non-anthracycline regimens (OR 5.43 95% confidence interval: 2.34, 12.62), anthracycline versus mitoxantrone (OR 2.88 95% confidence interval: 1.29, 6.44), and bolus versus continuous anthracycline infusions (OR 4.13 95% confidence interval: 1.75, 9.72). Risk of clinical cardiotoxicity was significantly lower with epirubicin versus doxorubicin (OR 0.39 95% confidence interval: 0.20, 0.78), liposomal versus non-liposomal doxorubicin (OR 0.18 95% confidence interval: 0.08, 0.38) and with a concomitant cardioprotective agent (OR 0.21 95% confidence interval: 0.13, 0.33). No statistical heterogeneity was found for these pooled analyses. A similar pattern of results were found for subclinical cardiotoxicity; with risk significantly greater with anthracycline containing regimens and bolus administration; and significantly lower risk with epirubicin, liposomal doxorubicin versus doxorubicin but not epirubicin, and with concomitant use of a cardioprotective agent. Low to moderate statistical heterogeneity was found for two of the five pooled analyses, perhaps due to the different criteria used for reduction in Left Ventricular Ejection Fraction. Meta-analyses of any cardiotoxicity (clinical and subclinical) showed moderate to high statistical heterogeneity for four of five pooled analyses; criteria for any cardiotoxic event differed between studies. Nonetheless the pattern of results was similar to those for clinical or subclinical cardiotoxicity described above.

Conclusions

Evidence is not sufficiently robust to support clear evidence-based recommendations on different anthracycline treatment regimens, or for routine use of cardiac protective agents or liposomal formulations. There is a need to improve cardiac monitoring in oncology trials.