Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy.
BACKGROUND
The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. To prevent this cardiotoxicity, different anthracycline dosage schedules have been studied.


OBJECTIVE
To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules (i.e. peak doses and infusion durations) in cancer patients.


METHODS
We searched the databases of The Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2008), MEDLINE (1966 to November 2008) and EMBASE (1980 to November 2008). Also, we searched reference lists of relevant articles, conference proceedings and ongoing trials databases.


METHODS
Randomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in cancer patients (children and adults).


METHODS
Two authors independently performed the study selection, the risk of bias assessment and the data-extraction.


RESULTS
We identified seven RCTs addressing different anthracycline infusion durations. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of 6 hours or longer as compared to a shorter infusion duration (relative risk (RR) = 0.27; 95% confidence interval (CI) 0.09 to 0.81; 5 studies; 557 patients). The majority of patients 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). In none of the studies a significant difference in the occurrence of clinical heart failure was identified. All patients included in these studies were adults with different solid tumours.


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.No significant difference in the occurrence of clinical heart failure was identified in patients treated with a doxorubicin peak dose of less than 60 mg/m(2) or 60 mg/m(2) or more. For the other identified peak doses only one RCT was available, so no definitive conclusions can be made about the occurrence of cardiotoxicity. More high quality research is needed, both in children and adults and in leukaemias and solid tumours.
van Dalen
Elvira C
EC
Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, PO Box 22660 (room F8-257), Amsterdam, Netherlands, 1100 DD.
van der Pal
Helena J H
HJ
Caron
Huib N
HN
Kremer
Leontien Cm
LC
D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D002303:Cardiac Output, Low / Q000139:chemically induced / Q000517:prevention & control; D002648:Child; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic