Safety and Treatment Efficacy of Systemic, Locoregional, and Nanoparticle Encapsulated Anthracycline Chemotherapy: Insights Into Cardiotoxicity

Cancer survivors are at an increased risk for major adverse cardiovascular events and cardiovascular disease mortality compared with the general population. In fact, emerging evidence suggests that cardiovascular disease is the leading cause of mortality 10 years into survivorship for some cancer populations. While this heightened cardiovascular risk undoubtedly involves a variety of factors, antineoplastic therapies, such as anthracyclines, are known to contribute significantly to this pathology. As such, modalities that improve the localization of treatments to the tumor while simultaneously minimizing off-target effects on noncancerous cells are greatly needed. Approaches in which anthracyclines are injected directly into tumor-fed arterioles (locoregional/intra-arterial administration) or are encapsulated in tumor-directed nanoparticles have gained prominence in certain cancers. Such therapies should direct cardiotoxic chemotherapy away from sites of potential toxicity while leaving the tumor exposed. However, current clinical findings on the efficacy and cardiovascular safety of these treatments remain inconclusive, and their use for many cancers is limited. This narrative review aims to highlight current clinical findings that have evaluated the safety and efficacy of locoregional and nanoparticle-mediated anthracycline administration as they compare with systemic delivery and identify avenues to be explored by future research.