Evaluating the Cardioprotective Effects of Melatonin in Nonmetastatic Breast Cancer Patients Receiving Doxorubicin Plus Cyclophosphamide: A Triple-Blind, Placebo-Controlled Randomized Controlled Trial Publisher



Mousavinia SM ; Larti F ; Ranjbar H ; Lashkari M ; Roudini K ; Emami AH ; Esfandbod M ; Jahangardrafsanjani Z
Source: Iranian Journal of Pharmaceutical Research Published:2025

Abstract

Background: Doxorubicin, one of the most widely used chemotherapy drugs, has several side effects, including cardiotoxicity. Objectives: We investigated the effect of melatonin on doxorubicin-induced cardiotoxicity in breast cancer patients treated with a regimen of doxorubicin plus cyclophosphamide (AC). Methods: This is a triple-blind, placebo-controlled, randomized clinical trial conducted at the Cancer Institute of Imam Khomeini Hospital, Tehran University of Medical Sciences. Using the block randomization method, 63 breast cancer patients participated in the study and were randomly divided into two groups of 32 and 31, receiving melatonin (10 mg) and a placebo, respectively. The chemotherapy regimen for these patients included doxorubicin 60 mg/m2. Melatonin or placebo was started concurrently with doxorubicin at bedtime in the first cycle of chemotherapy and continued until one week after the end of the last cycle of chemotherapy. Echocardiography was performed before initiation and one week after the last chemotherapy session. Also, the cardiac troponin I (cTnI) and creatine kinase-myoglobin binding (CK-MB) levels were measured upon study recruitment, one week after the second and fourth chemotherapy sessions. Results: The echocardiography showed that after the intervention, the left ventricular ejection fraction (LVEF) was higher in the melatonin group than in the placebo group, but it was insignificant. Meanwhile, the average global longitudinal strain (GLS) was significantly higher in the melatonin group than in the placebo group at the end of the study. The cTnI and CK-MB biomarker levels were lower in the melatonin group compared to the placebo group. These changes were significant for cTnI but not for CK-MB. Conclusions: Melatonin may be effective in the prevention of doxorubicin-induced cardiotoxicity based on the improvement in GLS and biomarker levels. © 2025 Elsevier B.V., All rights reserved.