title: Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer.
abstract: BACKGROUND
  Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity.
  
  
  OBJECTIVE
  To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions or no treatment.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, issue 1), MEDLINE/PubMed (1949 to May 2011) and EMBASE/Ovid (1980 to May 2011) for potentially relevant articles. We additionally searched reference lists of relevant articles, conference proceedings and ongoing trial databases.
  
  
  METHODS
  Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions or no treatment.
  
  
  METHODS
  Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments which were checked by another review author.
  
  
  RESULTS
  We identified two RCTs. One trial (135 patients) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline induced cardiac dysfunction. The other trial (68 patients) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, ATP, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations.The RCT on enalapril showed no (statistically) significant differences in overall survival, mortality due to heart failure, development of clinical heart failure and quality of life between treatment and control group. A post-hoc analysis showed a decrease (i.e. improvement) in one measure of cardiac function (left ventricular end systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Patients treated with enalapril had a higher risk of dizziness or hypotension (RR 7.17, 95% CI 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013).The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function and adverse events between treatment and control group.
  
  
  CONCLUSIONS
  For the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction, only one RCT is available. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side-effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity.For the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT is available. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatment on echocardiographic function and clinical outcomes.We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors.High-quality studies should be performed.
authors: Department of Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, PO Box 22660 (room A3-246), Amsterdam, Netherlands, 1100 DD.
authors: Elske
authors: E
authors: Sieswerda
authors: Elvira C
authors: EC
authors: van Dalen
authors: Aleida
authors: A
authors: Postma
authors: Daniel Kl
authors: DK
authors: Cheuk
authors: Huib N
authors: HN
authors: Caron
authors: Leontien Cm
authors: LC
authors: Kremer
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002648:Child; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D010725:Phosphocreatine / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D017741:Survivors
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D010725:Phosphocreatine; D004656:Enalapril