Cardioprotective interventions for cancer patients receiving anthracyclines
Abstract
Background
Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose‐dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied.
Objectives
The objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines.
Search methods
We searched the databases of CENTRAL (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to August 2002) and EMBASE (1980 to August 2002). In addition, we handsearched reference lists and conference proceedings of the International Society for Paediatric Oncology (SIOP) and the American Society of Clinical Oncology (ASCO) (1998 to 2002).
Selection criteria
Randomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional or placebo therapy in cancer patients (children and adults) receiving anthracyclines.
Data collection and analysis
Two reviewers independently performed the study selection, quality assessment and data‐extraction including adverse effects.
Main results
We identified RCTs for 5 cardioprotective agents: N‐acetylcysteine (1 study; 54 patients), phenetylamines (2 studies; 100 patients), coenzyme Q10 (1 study; 20 patients), combination of vitamin E, vitamin C and N‐acetylcysteine (1 study; 14 patients) and dexrazoxane (6 studies; 1013 patients). All studies had methodological limitations. Due to the insufficient number of studies, for the first four mentioned cardioprotective agents pooling of the results was impossible. None of the individual studies showed a cardioprotective effect. The meta‐analysis of the dexrazoxane‐studies showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (Relative Risk (RR) = 0.28, 95% Confidence Interval (CI) 0.18 to 0.42, P < 0.00001). No statistically significant difference in response rate between the dexrazoxane and control group was found (RR = 0.88, 95% CI 0.77 to 1.01, P = 0.06), but there was some suggestion that patients treated with dexrazoxane might have a lower anti‐tumour response rate. Our meta‐analysis of survival showed no significant difference between the dexrazoxane and control group. For adverse effects pooling was impossible. However, no important differences in the occurrence of side effects were found. The majority of the patients included in this meta‐analysis were adults with advanced breast cancer.
Authors' conclusions
For cardioprotective agents for which pooling was impossible no high quality evidence was available and therefore, no definitive conclusions can be made about their efficacy. Dexrazoxane prevents heart damage, however there was some suggestion that patients treated with dexrazoxane might have a lower anti‐tumour response rate. There was no significant difference in survival between the dexrazoxane and control group. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines. However, for each individual patient clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of a lower response rate.
PICOs
Plain language summary
Dexrazoxane prevents heart damage in patients receiving anthracycline treatment but it is unclear if it reduces anti‐tumour response rate. There is a lack of evidence available for other cardioprotective agents.
Anthracyclines are among the most effective chemotherapy treatments available for various types of cancer. However, there is a risk of damage to the heart (cardiotoxicity) depending on the cumulative dose. A number of agents are available in an effort to prevent this damage. The reviewers found that for many of the agents there was no high quality evidence available and were unable to draw conclusions. For dexrazoxane, the reviewers found that it prevented heart damage, however patients treated with it might have a lower anti‐tumour response rate to the anthracycline treatment. Dexrazoxane had no effect on survival and no difference in the occurance of adverse effects was noted. Further research is needed.
