title: 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.
  
  
  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 Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE (1966 to November 2010) and EMBASE (1980 to November 2010) databases. In addition, we handsearched reference lists, conference proceedings of the International Society of Paediatric Oncology (SIOP) and American Society of Clinical Oncology (ASCO) meetings (1998 to 2010) and ongoing trials registers.
  
  
  METHODS
  Randomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional therapy or placebo in cancer patients (children and adults) receiving anthracyclines.
  
  
  METHODS
  Two review authors independently performed the study selection, risk of bias assessment and data extraction including adverse effects.
  
  
  RESULTS
  We identified RCTs for the eight cardioprotective agents N-acetylcysteine, phenethylamines, coenzyme Q10, a combination of vitamins E and C and N-acetylcysteine, L-carnitine, carvedilol, amifostine and dexrazoxane (mostly for adults with advanced breast cancer). All studies had methodological limitations and for the first seven agents there were too few studies to allow pooling of results. None of the individual studies showed a cardioprotective effect. The 10 included studies on dexrazoxane enrolled 1619 patients. The meta-analysis for dexrazoxane showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (risk ratio (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 groups. The results for adverse effects were ambiguous. No significant difference in the occurrence of secondary malignancies was identified.
  
  
  CONCLUSIONS
  No definitive conclusions can be made about the efficacy of cardioprotective agents for which pooling of results was impossible. Dexrazoxane prevents heart damage and no evidence for a difference in response rate or survival between the dexrazoxane and control groups was identified. The evidence available did not allow us to reach any definite conclusions about adverse effects. 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, clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects for each individual patient.
authors.affiliation: Department of Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, PO Box 22660 (room A3-273), Amsterdam, Netherlands, 1100 DD.
authors.forename: Elvira C
authors.initials: EC
authors.lastname: van Dalen
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.forename: Heather O
authors.initials: HO
authors.lastname: Dickinson
authors.forename: Leontien Cm
authors.initials: LC
authors.lastname: Kremer
mesh_terms: 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; D011929:Razoxane / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D011929:Razoxane