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Meta-Analysis
. 2010 May 12;2010(5):CD005006.
doi: 10.1002/14651858.CD005006.pub4.

Different anthracycline derivates for reducing cardiotoxicity in cancer patients

Elvira C van Dalen  1 , Erna Mc Michiels, Huib N Caron, Leontien Cm Kremer
Affiliations
Meta-Analysis

Different anthracycline derivates for reducing cardiotoxicity in cancer patients

Elvira C van Dalen et al. Cochrane Database Syst Rev. .

Abstract

Background: The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied.

Objectives: To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients.

Search strategy: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases.

Selection criteria: Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults).

Data collection and analysis: Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects.

Main results: We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified.

Authors' conclusions: We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Doxorubicin versus epirubicin, Outcome 1 Clinical heart failure.
1.2
1.2. Analysis
Comparison 1 Doxorubicin versus epirubicin, Outcome 2 Tumour response.
1.3
1.3. Analysis
Comparison 1 Doxorubicin versus epirubicin, Outcome 3 Progression‐free survival.
1.4
1.4. Analysis
Comparison 1 Doxorubicin versus epirubicin, Outcome 4 Overall survival.
1.5
1.5. Analysis
Comparison 1 Doxorubicin versus epirubicin, Outcome 5 Adverse effects: leukopenia grade 3 or 4.
1.6
1.6. Analysis
Comparison 1 Doxorubicin versus epirubicin, Outcome 6 Adverse effects: nausea / vomiting grade 3 or 4.
1.7
1.7. Analysis
Comparison 1 Doxorubicin versus epirubicin, Outcome 7 Adverse effects: alopecia grade 3 or 4.
2.1
2.1. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 1 Clinical heart failure.
2.2
2.2. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 2 Heart failure combined.
2.3
2.3. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 3 Tumour response.
2.4
2.4. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 4 Progression‐free survival.
2.5
2.5. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 5 Overall survival.
2.6
2.6. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 6 Adverse effects: anaemia grade >=3.
2.7
2.7. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 7 Adverse effects: thrombocytopenia grade >=3.
2.8
2.8. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 8 Adverse effects: neutropenia grade 4.
2.9
2.9. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 9 Adverse effects: neutropenic fever (fever >=38, neutropenia grade 4, IV antibiotics and/or hospitalisation).
2.10
2.10. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 10 Adverse effects: nausea/vomiting grade >=3.
2.11
2.11. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 11 Adverse effects: stomatitis/mucositis grade >=3.
2.12
2.12. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 12 Adverse effects: diarrhoea grade >=3.
2.13
2.13. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 13 Adverse effects: asthenia/fatigue grade 3.
2.14
2.14. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 14 Adverse effects: cutaneous grade 3.
2.15
2.15. Analysis
Comparison 2 Conventional doxorubicin versus liposomal‐encapsulated doxorubicin (myocet), Outcome 15 Adverse effects: infection grade >=3.
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Ventura 2005 {published data only}
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References to studies awaiting assessment

Burnell 2007 {published data only}
    1. Burnell MJ, Levine MN, Chapman JA, Bramwell V, Vandenberg T, Chalchal HI, et al. A phase III adjuvant trial of sequenced EC + filgrastim + epoetin‐alpha followed by paclitaxel compared to sequenced AC followed by paclitaxel compared to CEF in women with node‐positive or high‐risk node‐negative breast cancer (NCIC CTG MA.21). 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement): 550. 2007.
Knobloch 2008 {published data only (unpublished sought but not used)}
    1. Knobloch K, Tepe J, Rossner D, Lichtinghagen R, Luck HJ, Busch KH, et al. Combined NT‐pro‐BNP and CW‐Doppler ultrasound cardiac output monitoring (USCOM) in epirubicin and liposomal doxorubicin therapy. International Journal of Cardiology 2008;128:316‐25. - PubMed
NCT00002985 {published data only}
    1. Double‐Blind Randomized Evaluation of Clinical Benefits of DOXIL in Patients With AIDS‐Related Kaposi's Sarcoma Treated With DOXIL or DaunoXome. NCT00002985 on www.controlled‐trials.com.
NCT00022516 {published data only}
    1. Maintenance Chemotherapy In Hormone Non‐Responsive Breast Cancer, Assessment of Vascular Endothelial Growth Factor (VEGF), Soluble Her2 Protein (NRP, HER2‐ECD) and Vascular Cellular Adhesion Molecule‐1 (VCAM‐1) in Serum Samples. NCT0022516 on www.controlled‐trials.com.
NCT00431795 {published data only (unpublished sought but not used)}
    1. A multicentre randomized phase II study of second line chemotherapy with epirubicin (farmorubicin) versus the pegylated liposomal doxorubicin in advanced breast cancer patients. NCT00431795 on www.controlled‐trials.com.
NCT00516425 {published data only (unpublished sought but not used)}
    1. Adjuvant cytotoxic chemotherapy in older women. NCT00516425 on www.controlled‐trials.com.
NCT00536393 {published data only (unpublished sought but not used)}
    1. Phase III study of treatment of disseminated and aggresive lymphoma R CHOP versus R CLOP (with liposomal doxorubicin). NCT00536393 on www.controlled‐trials.com.
Northfelt 1996 {published data only (unpublished sought but not used)}
    1. Northfelt DW, Martin FJ, Working P, Volberding PA, Russell J, Newman M, et al. Doxorubicin encapsulated in liposomes containing surface‐bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS‐related Kaposi's sarcoma. Journal of Clinical Pharmacology 1996;36:55‐63. - PubMed

References to ongoing studies

NCT00575406 {published and unpublished data}
    1. Multicentre study to determine the cardiotoxicity of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristin and prednisolone) compared to R‐COMP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristin and prednisolone) in patients with diffuse large B‐cell lymphoma (NHL‐14). NCT00575406 on www.controlled‐trials.com.

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References to other published versions of this review

Van Dalen 2006b
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