Different anthracycline derivates for reducing cardiotoxicity in cancer patients

Anthracyclines are among the most effective chemotherapy treatments available for various types of cancer. However, there is a risk of damage to the heart depending on the cumulative dose. In an effort to prevent heart damage different anthracycline derivates (like doxorubicin, daunorubicin, and epirubicin) are being used.

The authors found that for the use of many different combinations of anthracycline derivates there was no high quality evidence available and it was impossible to draw conclusions.

For the use of epirubicin versus doxorubicin, there was some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin. There is no evidence which suggests a difference in anti-tumour response rate and survival between epirubicin and doxorubicin. No conclusions can be made regarding adverse effects. There are no data for children and patients with leukaemia. Further research is needed. For the use of doxorubicin versus liposomal-encapsulated doxorubicin, the authors found a significantly lower rate of both clinical heart failure and subclinical heart failure (i.e. various cardiac abnormalities, diagnosed with different diagnostic methods like echocardiography in asymptomatic patients) in patients treated with liposomal-encapsulated doxorubicin. There is no evidence which suggests a difference in anti-tumour response rate and survival between doxorubicin and liposomal-encapsulated doxorubicin. A lower rate of adverse effects was identified in patients treated with liposomal-encapsulated doxorubicin. There are no data for children and patients with leukaemia. Further research is needed.

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.

Read the full 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.

Share/Save