Morning administration of anthracyclines is associated with a lower risk of cancer therapy-related cardiac dysfunction

Abstract

Aims Pre-clinical studies point towards an administration time-dependency of anthracycline-induced cancer therapy-related cardiac dysfunction (CTRCD). This retrospective study aimed to investigate the association between time-of-day of AC administration and CTRCD. Methods Patients from two cardio-oncology outpatient clinics, treated with ACs for any malignancy, were included. Percentage of and results afternoon AC administration was calculated: cumulative dose administered in the afternoon (12 p.m.–11:59 p.m.)/total cumulative dose. Three groups were defined: morning group ≥ 50% of ACs in the morning (12 a.m.–11:59 a.m.), afternoon group ≥ 50% of ACs in the afternoon, and intermediate group = exactly 50% of ACs in the morning and afternoon. Associations between AC timing and occurrence of CTRCD and heart failure (HF) were assessed using survival analyses. Of 270 included patients, 66 developed CTRCD and 17 developed HF. Compared with the morning group, the afternoon group had a higher risk of developing CTRCD: hazard ratio (HR) 2.88 (95% CI: 1.52–5.44). When considering percentage of ACs administered in the afternoon as a continuous variable, the HR for developing CTRCD was 1.14 (95% CI: 1.04–1.24) for each subsequent 10% of afternoon administration. Results were consistent across sensitivity analyses of age, sex, body mass index, malignancy type, cumulative AC dose, and HFA-ICOS risk score. Congruently, the continuous variable of afternoon AC administration was associated with higher risk of HF: HR = 1.19 (95% CI: 1.01–1.41). Conclusion Afternoon administration of ACs is associated with an increased risk of developing CTRCD and HF, suggesting that morning administration may be preferred. Before widespread implementation, these findings should be confirmed in an RCT. Lay summary This study investigated if the amount of cardiac damage is associated with the administration time-of-day of anthracyclines, which are chemotherapeutics used in cancer treatment and can cause severe damage to the heart. • In a real-world data cohort including 270 patients, in 66 patients anthracycline-induced cardiac damage was detected, and of these patients, 17 developed heart failure.