Protecting against anthracycline‐induced myocardial damage: a review of the most promising strategies

Abstract

SummaryOver the last 40 years, great progress has been made in treating childhood and adult cancers. However, this progress has come at an unforeseen cost, in the form of emerging long-term effects of anthracycline treatment. A major complication of anthracycline therapy is its adverse cardiovascular effects. If these cardiac complications could be reduced or prevented, higher doses of anthracyclines could potentially be used, thereby further increasing cancer cure rates. Moreover, as the incidence of cardiac toxicity resulting in congestive heart failure or even heart transplantation dropped, the quality and extent of life for cancer survivors would improve. We review the proposed mechanisms of action of anthracyclines and the consequences associated with anthracycline treatment in children and adults. We summarise the most promising current strategies to limit or prevent anthracycline-induced cardiotoxicity, as well as possible strategies to prevent existing cardiomyopathy from worsening.

Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline‐related congestive heart failure after childhood cancer

“…A nthracycline-related congestive heart failure (CHF) is an important long-term complication among childhood cancer survivors. Preclinical abnormalities of cardiac structure and function have been reported in 60% of patients who received anthracyclines, 1 and the risk of overt, clinically symptomatic CHF has been estimated at from 4% to 5%. 2 Potential risk factors for anthracycline-related CHF include total cumulative dose, being a woman, radiation therapy, and younger age at diagnosis.…”

“…6 NQO1 also contributes to maintain intracellular levels of bioactive vitamin E in situations of oxidative stress, and vitamin E administration has been evaluated as a cardioprotective strategy during therapy with anthracyclines. 1 Therefore, we hypothesized that relatively low NQO1 activity dictated by the NQO1*2 allele (q 5 0.16-0.20) may have an impact on the risk of anthracycline-related CHF. In the human myocardium, cytosolic carbonyl reductases (CBRs), and aldo/keto reductases (AKRs) catalyze the 2-electron reduction of the anthracycline side chain C-13 carbonyl group to form cardiotoxic alcohol metabolites (eg, doxorubicinol, daunorubicinol).…”

Pretreatment Effect of Running Exercise on HSP70and DOX-Induced Cardiotoxicity

“…Several strategies for detecting and preventing cardiotoxicity have been developed, some of which are more effective than others. Including limiting cumulative dose, altering anthracycline administration, using anthracycline analogues, adding cardioprotectants to the regimen and employing nutritional supplements (Wouters et al, 2005). Prior endurance exercise as a nonpharmacological strategy may be possible that promotes defense against DOX cardiotoxicity 2011;Wonders et al, 2008).…”

The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study

“…Treatment with DOX is limited by a dose-dependent cardiotoxicity, which may lead to late side effects resulting in severe morbidity and mortality (Steinherz et al, 2001;Lipshultz et al, 2005). Although the 5-year survival of childhood cancer has improved from 30 to 70% in the last 40 years, the risk of death from cardiac events in these survivors is eight times higher than that in the normal population (Wouters et al, 2005). Besides this, combining DOX with other anticancer drugs, for example, taxanes and trastuzumab, increases efficacy, but unfortunately also augments cardiotoxicity (Seidman et al, 2002;Minotti et al, 2004).…”