Short-Term, Cycle-Synchronized Adjunctive Therapy With Crocus Total Glucosides Tablets for Cardiac Protection Against Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Crocin shows cardioprotective potential against chemotherapy-related cardiotoxicity, but clinical evidence for cycle-synchronized intervention remains limited. This randomized, double-blind, placebo-controlled trial investigated whether crocus total glucosides tablets (CTGT) administered synchronously with chemotherapy could prevent cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients. A total of 120 patients were randomly assigned (1:1) to receive either CTGT or placebo for 8 days/cycle, starting 1 day before chemotherapy. Primary endpoints were 6-month relative decline in left ventricular global longitudinal strain (ΔLVGLS%) and change in left ventricular ejection fraction (ΔLVEF); secondary endpoints included 3-month measures, LVEF and LVGLS, CTRCD incidence [LVEF<50% or ΔLVGLS%>15% or elevated high-sensitivity cardiac troponin I (hs-cTnI)/N-terminal pro-B-type natriuretic peptide (NT-proBNP)], and severe arrhythmias. Based on the intention-to-treat analysis, CTGT significantly attenuated the 6-month ΔLVGLS% compared with placebo (−6.55 ± 10.85 vs. −12.63 ± 13.49%, p = 0.009), whereas ΔLVEF did not differ significantly (−3.67 ± 5.75 vs. −2.40 ± 5.47%, p = 0.220). Similar results were observed at 3 months (ΔLVGLS%: −3.91 ± 10.18 vs. −7.76 ± 10.64%, p = 0.047). CTGT also reduced the proportion of patients with ΔLVGLS%>15% (18.3 vs. 40.0%, p = 0.009) and the incidence of CTRCD (21.7 vs 46.7%, p = 0.004). An 8-day, cycle-synchronized CTGT regimen attenuates LVGLS decline and reduces CTRCD incidence, highlighting its cardioprotective effect during breast cancer chemotherapy (NCT05504148).

Keywords

breast cancer / cancer therapy-related cardiac dysfunction / Crocus total glucosides tablets / left ventricular global longitudinal strain / left ventricular ejection fraction

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