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Meta-Analysis
. 2016 Mar 3;3(3):CD005008.
doi: 10.1002/14651858.CD005008.pub4.

Different dosage schedules for reducing cardiotoxicity in people with cancer receiving anthracycline chemotherapy

Elvira C van Dalen  1 , Helena J H van der Pal, Leontien C M Kremer
Affiliations
Meta-Analysis

Different dosage schedules for reducing cardiotoxicity in people with cancer receiving anthracycline chemotherapy

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

Abstract

Background: This review update has been managed by both the Childhood Cancer and Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Groups.The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. To prevent this cardiotoxicity, different anthracycline dosage schedules have been studied.

Objectives: To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules (that is peak doses and infusion durations) in people with cancer.

Search methods: We searched the databases of the Cochrane Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 11, 2015), MEDLINE (1966 to December 2015), and EMBASE (1980 to December 2015). We also searched reference lists of relevant articles, conference proceedings, experts in the field, and ongoing trials databases.

Selection criteria: Randomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in people with cancer (children and adults).

Data collection and analysis: Two review authors independently performed the study selection, the 'Risk of bias' assessment, and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.

Main results: We identified 11 studies: 7 evaluated different infusion durations (803 participants), and 4 evaluated different peak doses (5280 participants). Seven studies were RCTs addressing different anthracycline infusion durations; we identified long-term follow-up data for one of the trials in this update. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of six hours or longer as compared to a shorter infusion duration (risk ratio (RR) 0.27; 95% confidence interval 0.09 to 0.81; 5 studies; 557 participants). The majority of participants included in these studies were adults with different solid tumours. For different anthracycline peak doses, we identified two RCTs addressing a doxorubicin peak dose of less than 60 mg/m(2) versus 60 mg/m(2) or more, one RCT addressing a liposomal doxorubicin peak dose of 25 mg/m(2) versus 50 mg/m(2), and one RCT addressing an epirubicin peak dose of 83 mg/m(2) versus 110 mg/m(2). A significant difference in the occurrence of clinical heart failure was identified in none of the studies. The participants included in these studies were adults with different solid tumours. High or unclear 'Risk of bias' issues were present in all studies.

Authors' conclusions: An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children.We identified no significant difference in the occurrence of clinical heart failure in participants treated with a doxorubicin peak dose of less than 60 mg/m(2) or 60 mg/m(2) or more. Only one RCT was available for the other identified peak doses, so we can make no definitive conclusions about the occurrence of cardiotoxicity. More high-quality research is needed, both in children and adults and in leukaemias and solid tumours.

PubMed Disclaimer

Conflict of interest statement

Elvira C van Dalen: None known.

Helena JH van der Pal: None known.

Leontien CM Kremer: None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Infusion duration less than 6 hours versus infusion duration 6 hours or more, Outcome 1: Clinical heart failure
1.2
1.2. Analysis
Comparison 1: Infusion duration less than 6 hours versus infusion duration 6 hours or more, Outcome 2: (Sub)clinical heart failure combined
1.3
1.3. Analysis
Comparison 1: Infusion duration less than 6 hours versus infusion duration 6 hours or more, Outcome 3: Response rate
1.4
1.4. Analysis
Comparison 1: Infusion duration less than 6 hours versus infusion duration 6 hours or more, Outcome 4: Overall survival
2.1
2.1. Analysis
Comparison 2: Doxorubicin peak dose less than 60 mg/m2 versus 60 mg/m2 or more, Outcome 1: Clinical heart failure
2.2
2.2. Analysis
Comparison 2: Doxorubicin peak dose less than 60 mg/m2 versus 60 mg/m2 or more, Outcome 2: Overall survival
2.3
2.3. Analysis
Comparison 2: Doxorubicin peak dose less than 60 mg/m2 versus 60 mg/m2 or more, Outcome 3: Adverse effects other than cardiac damage
3.1
3.1. Analysis
Comparison 3: Liposomal doxorubicin (Caelyx) peak dose 25 mg/m2 versus 50 mg/m2, Outcome 1: Response rate (defined as objective palliative tumour response (i.e. decrease in PSA levels of >= 50%))
3.2
3.2. Analysis
Comparison 3: Liposomal doxorubicin (Caelyx) peak dose 25 mg/m2 versus 50 mg/m2, Outcome 2: Adverse effects other than cardiac damage
4.1
4.1. Analysis
Comparison 4: Epirubicin peak dose 110 mg/m2 versus 83 mg/m2, Outcome 1: Clinical heart failure
4.2
4.2. Analysis
Comparison 4: Epirubicin peak dose 110 mg/m2 versus 83 mg/m2, Outcome 2: Adverse effects other than cardiac damage
See this image and copyright information in PMC

Update of

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References to other published versions of this review

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