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 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).
  
  
  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 reviewers independently performed the study selection, quality assessment and data-extraction including adverse effects.
  
  
  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.
  
  
  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.
authors.affiliation: Pediatric Oncology, Emma Children's Hospital / Academic Medical Center (room F8-257), PO Box 22660, Amsterdam, Netherlands, 1100 DD. E.C.vanDalen@amc.uva.nl
authors.forename: E C
authors.initials: EC
authors.lastname: van Dalen
authors.forename: H N
authors.initials: HN
authors.lastname: Caron
authors.forename: H O
authors.initials: HO
authors.lastname: Dickinson
authors.forename: L C M
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
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents