BACKGROUND: Anthracycline-based chemotherapy, such as Doxorubicin (DOX), often induces cardiotoxicity in cancer patients, which compromises their health and quality of life. OBJECTIVE: This study aimed to verify the effects of exercise concomitant with prolonged administration of DOX on improving cardiotoxicity. METHODS: A systematic literature search in MedLine, PubMed, Web of Science, and Scopus databases was performed from inception until November 2023, strictly following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Preclinical randomized controlled trials related to exercise, cardiotoxicity, and DOX were included. RESULTS: Eight studies were included in the systematic review and 7 were selected for metaanalysis. By evaluating the Fractional Shortening (FS), it was possible to verify that exercise as complementary therapy provided a cardioprotective effect when compared to DOX combined with sedentary behavior (heterogeneity: I² = 53%
tau² = 0.19
p = 0.03
overall effect: z = 2.69
p <
0.01). However, no additional benefits were observed for the Left Ventricular Ejection Fraction (LVEF) (heterogeneity: I² = 82%
tau² = 1.43
p <
0.01
overall effect: z = 1.42
p = 0.15). CONCLUSION: The included studies demonstrated exercise to have a cardioprotective effect on rodents, mainly on FS. However, there is a lack of high-level evidence to guide exercise prescription in clinical practice to improve cardiotoxicity associated with DOX administration.