Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy

Abstract

The risk and mechanism of chemotherapy-induced cardiotoxicity (CTX) vary depending on the type and intensity of the anticancer regimen. Myriad chemotherapeutic drugs produce adverse cardiovascular effects such as arterial hypertension, heart failure, and thromboembolic events. Among the numerous classes of these drugs, anthracyclines have been studied most extensively because of their overt cardiovascular effects and the high associated incidence of heart failure. However, CTX might also be caused by other types of chemotherapeutic agents, including alkylating agents (cyclophosphamide, ifosfamide), platinum agents, antimetabolites (5-fluorouracil, capecitabine), antibiotics (mitoxantrone, mitomycin, bleomycin), and antimicrotubule agents (taxanes). Here, we review the incidence, clinical impact, and potential mechanisms of CTX associated with nonanthracycline chemotherapy used for cancer patients. The published data support a marked increase in CTX risk, particularly with certain drugs such as 5-fluorouracil and cisplatin. Each anticancer regimen is associated with distinct modes of heart damage, both symptomatic and asymptomatic. However, the underlying mechanisms of CTX have been established only in a few cases, and only few nonanthracycline chemotherapeutics (mitoxantrone, mitomycin, ifosfamide) act through a recognizable mechanism and show a predictable dose dependence. Lastly, nonanthracycline chemotherapy can induce both chronic lesions, such as systolic dysfunction, and acute lesions, such as the ischemia that occurs within hours or days after treatment. An increased understanding of the incidence, mechanisms, and potential therapeutic targets of CTX induced by various nonanthracycline chemotherapeutic agents is clearly required.

Is it possible to cure childhood acute myeloid leukaemia without significant cardiotoxicity?

“…For example, the alkylating agent cyclophosphamide, used in AML treatment for conditioning in SCT, may cause cardiotoxicity (Madeddu et al, 2016). For example, the alkylating agent cyclophosphamide, used in AML treatment for conditioning in SCT, may cause cardiotoxicity (Madeddu et al, 2016).…”

The effect of oxaliplatin on heart tissue of the rats

“…Anthracyclines (eg., doxorubicin, epirubicin, daunorubicin, idarubicin) have been extensively studied because of the high incidence of cardiac insufficiency due to cardiotoxicity and significant cardiovascular effects [1,2]. However, cardiotoxicity may also occur with other chemotherapeutic agents including alkylating agents (cyclophosphamide, ifosfamide), platinum agents, antimetabolites (5-fluorouracil, capecitabine), antibiotics (mitoxantrone, mitomycin, bleomycin) and antimicrobial agents (taxanes) [3]. Although cardiotoxicity has been reported by oxidative stress induced by cisplatin-related reactive oxygen metabolites from platinum group chemotherapeutics, fewer studies have been reported on oxaliplatin(OXA) cardiotoxicity [4,5,6].…”

Cancer treatment associated cardiac toxicities

“…21 Other potential causes are endothelial damage and transient stress-induced cardiomyopathies, as well as coronary thrombosis and arteritis, leading to manifestations such as asymptomatic EKG changes to acute pulmonary edema, arrhythmias, and myocardial infarctions with ST segment and cardiac biomarker elevations. 22 The risk of cardiotoxicity of 5-FU depends on the route and schedule of administration but is not necessarily dependent on underlying cardiovascular disease. 19 Several studies in animal models have shown that 5-FU administration can lead to depletion of high energy phosphates in both a time and dosing dependent fashion which may be the etiology of angina.…”