Abstract: In the original version of the review we identified two RCTs; in this update we identified no additional studies. One trial (135 participants) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline-induced cardiac dysfunction. The other trial (68 participants) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, adenosine triphosphate, 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 groups. A post-hoc analysis showed a decrease (that is 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. Participants treated with enalapril had a higher risk of dizziness or hypotension (risk ratio 7.17, 95% confidence interval 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 groups. Only one trial evaluated the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction. 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. Only one trial evaluated the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatments 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.

Plain-language summary: We identified two randomised studies evaluating two different drugs in two different types of patients. One of these drugs, an angiotensin-converting enzyme (ACE) inhibitor (enalapril), had a short-term beneficial effect on heart function in survivors of childhood cancer with asymptomatic cardiac problems caused by anthracyclines compared with placebo. However, the drug had no significant beneficial effect on other important outcomes and was associated with side effects such as dizziness and fatigue. This study was of reasonable/good quality. The other study was of low quality and found no effect of a short treatment with phosphocreatine in childhood leukaemia patients with symptomatic or asymptomatic cardiac problems compared with a control treatment with vitamin C, adenosine triphosphate, vitamin E, and oral coenzyme Q10. We could make no definitive conclusions about treatment options for anthracycline-induced cardiac problems in childhood cancer patients and survivors. High-quality studies are needed to determine if there are drugs that improve heart function in these patients.