Chronotherapy as a novel strategy to limit anthracycline-induced cardiotoxicity

Abstract Anthracycline cardiotoxicity is a severe chemotherapeutic side effect that can lead to heart failure in cancer patients and survivors. Chronomodulated chemotherapy is a promising preventive strategy that encompasses the adjustment of anthracycline administration time to the circadian rhythms (24-hour rhythms) of the body. Circadian rhythms play a major role in cardiovascular physiology and disease and may lead to a time-dependent variation in cardiac sensitivity to anthracyclines. In this review, all available evidence on the topic of chronomodulated anthracyclines for cardiotoxicity reduction and/or oncological efficacy enhancement is summarized. In total, 3 in vitro studies, 12 animal studies, and 9 clinical studies were included. Potential mechanistic explanations involved 24-hour variation in oxidative stress regulation, DNA damage repair, and systemic or intracellular pharmacokinetics. We identified a hypothesized optimal time frame from 3 to 11 AM for anthracycline administration in humans, based on extrapolation of findings in animal studies.