Cardioprotective interventions for cancer patients receiving anthracyclines.
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.


OBJECTIVE
The objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines.


METHODS
We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2007), MEDLINE (1966 to April 2007) and EMBASE (1980 to April 2007). In addition, we handsearched reference lists and conference proceedings of the SIOP and ASCO meetings (1998 to 2006).


METHODS
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.


METHODS
Two review authors independently performed the study selection, quality assessment and data-extraction including adverse effects.


RESULTS
We identified RCTs for seven cardioprotective agents: N-acetylcysteine, phenetylamines, coenzyme Q10, combination of vitamins E and C and N-acetylcysteine, L-carnitine, carvedilol and dexrazoxane (mostly adults with advanced breast cancer). All studies had methodological limitations. For the first six agents, there were too few studies to allow pooling of results. None of the individual studies showed a cardioprotective effect. The nine included studies of dexrazoxane enrolled 1403 patients. The meta-analysis of dexrazoxane showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (Relative Risk (RR) 0.29, 95% CI 0.20 to 0.41). No evidence was found for a difference in response rate or survival between the dexrazoxane and control group. Only for one adverse effect (abnormal white blood cell count at nadir) a difference in favour of the control group was identified.


CONCLUSIONS
For cardioprotective agents for which pooling was impossible, no definitive conclusions can be made about their efficacy. Dexrazoxane prevents heart damage and no evidence for a difference in response rate or survival between the dexrazoxane and control group was identified. Only for an abnormal white blood cell count at nadir a clearly significant difference in favour of the control group was identified. 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 adverse effects.
van Dalen
E C
EC
Emma Children's Hospital / Academic Medical Center (room F8-257), Pediatric Oncology, Meibergdreef 9, PO Box 22660, Amsterdam, Netherlands, 1100 DD. E.C.vanDalen@amc.uva.nl
Caron
H N
HN
Dickinson
H O
HO
Kremer
L C M
LC
D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D019610:Cytoprotection; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents