Anthracycline induced cardiotoxicity: A systematic review

Abstract

Cancer cure currently involves a combination of integrative treatments; chemotherapy, radiotherapy, and surgery to extend life and deliver sustainability to the survivors. Among all the classes of chemotherapeutics, anthracycline group has multiple wellestablished therapeutic uses. Anthracyclines can be used as antibiotics and also effective over a wide spectrum of malignancies. However, they also possess undesired cardiac toxicity; being the major drawback of anthracycline chemotherapy, which restricts their clinical use. In retrospective, detrimental effects on heart associated with Anthracycline- Induced-Cardiotoxicity (AIC) is irreversible and a challenging concern in the field of cardio-oncology, considering other adverse effects. Despite its dose-limiting cardiotoxicity, anthracycline drugs are being widely used in chemotherapy because of their effectiveness over a broad spectrum of cancers and solid tumors. In addition to their versatile therapeutic activity, dose-dependent congestive heart failure and accumulation of toxic drug metabolites in cardiomyocytes may possibly be the worst consequences of cardiotoxicity caused by doxorubicin and other anthracyclines. Cardiotoxicity related to anthracyclines yet remains to be an intractable clinical conundrum for both cardiologists and oncologists. The mechanism of AIC possibly involves oxidative stress of myocardium triggered by free radicals and consequently may lead to apoptosis and lipid peroxidation, or involves immunologic responses. Notably, various other mechanisms may play an underlying role to predispose AIC. In the strategy to mitigate AIC, dexrazoxane has shown to have promising cardioprotective action and further used to lessen symptoms of cardiotoxicity. Although the impact of other cardioprotective agents such as β-blockers, ACEI (Angiotensin Converting Enzyme Inhibitors), and lipid lowering agents may reduce AIC to some degree, still significant cardiovascular complication may occur. Despite the reduction in cumulative dose of anthracyclines and concomitant use of iron chelator dexrazoxane, no other agent has absolute evidence in regard to treatment or protection against AIC. In this article, we reviewed the incidence of cardiotoxicity induced by mainly anthracyclines as well as their pathogenesis, detection, function of biomarkers and protective agents used to ameliorate cardiovascular complications. Besides, in particular, we found significant cardiovascular anomalies in ADR data of doxorubicin male patients and also a notable discrepancy in ADR data of docetaxel in different geographical regions.