Pharmacologic Prevention of Anthracycline-Induced Cardiomyopathy

Abstract

Anthracyclines are highly effective anticancer drugs. However, a major factor limiting their use in humans is a cumulative, dose-related cardiotoxicity which can result in a permanent loss of cardiomyocytes, which ultimately leads to asymptomatic and symptomatic heart failure. Experiences with various approaches to reduce the cardiotoxicity of anthracyclines without jeopardizing their antineoplastic effects have been reported in the oncology literature. This article reviews the etiology and natural history of anthracycline-induced cardiotoxicity and provides options available for limiting and/or preventing cardiotoxicity.

Favourable outcome of patients with childhood acute promyelocytic leukaemia after treatment with reduced cumulative anthracycline doses

“…To reduce the risk of developing clinical heart failure, which is approximately 5% at 15 years after anthracycline therapy for childhood cancer (Kremer et al , 2001; Lipshultz et al , 2008), the AML‐BFM study group limited the cumulative anthracycline dose to 350 mg/m 2 in most APL patients; furthermore, those anthracyclines were used that might have a lower cardiotoxicity per se [e.g. liposomal DNR (DaunoXome ® , Gilead, Foster City, CA)] and, in addition, were administered as a continuous infusion over 2–4 h (Maradia & Guglin, 2009). Follow‐up time of long‐term cardiotoxicity data for APL patients is currently still too short and the number of patients too small to provide definitive conclusions at this point.…”

Efficiency of Atorvastatin in the Protection of Anthracycline-Induced Cardiomyopathy

“…Newspapers focus on fatalities occurring in elite/national-level professional athletes, whereas reports of SCDs in the much larger population of adolescents/adults engaged in nonprofessional/ regional sports are usually overlooked. Moreover, an increase in the number of sports-related fatal events in more recent years in Western countries has been reported, a phenomenon that simply reflects enhanced public recognition due to increased media attention (3). This may also explain the relative lower prevalence of fatal events reported in the past decades and confirms the unreliability of estimating the time trend of SCDs in athletes based only on media reporting.…”

“…Strategies have been proposed to reduce ANT-induced cardiotoxicity, including continuous instead of bolus infusion, liposomal ANT administration, and addition of iron chelator dexrazoxane to chemotherapy regime. Although data are inconclusive, various agents have been experimented with to provide protection against ANT-induced CMP both in animal models and humans (3,4). Statins have been shown to decrease atherosclerosis-related morbidity and mortality.…”

The role of the proteasome in heart disease

“…Its major side effect is cardiotoxicity when used as anti-malignance agent, preventing Dox from being more effectively or broadly used [117, 118]. To date the mechanism by which Dox induces cardiotoxicity remains poorly understood.…”