Ilse R. Kelters, Markella I Printezi, Annabelle Ballesta, Pieterjan Dierickx, Yvonne Koop, Pasquale F. Innominato, Françis Lévi, Jacqueline Van Dam, Pieter A. Doevendans, Alwin D. R. Huitema, Arco J. Teske, Anne M. May, Joost P. G. Sluijter, Linda W. van Laake
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.