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Evaluating the role of montelukast on doxorubicin-induced cardiotoxicity in breast cancer patients

Support Care Cancer. 2025 Oct 1;33(10):897. doi: 10.1007/s00520-025-09947-z.

ABSTRACT

PURPOSE: Doxorubicin (DOX), a prominent anthracycline, is used to treat malignancies, but its cardiotoxicity restricts its therapeutic application. This study examined the potential protective effects of montelukast (ML), an anti-asthmatic drug with anti-inflammatory characteristics, against doxorubicin-induced cardiotoxicity (DIC) in breast cancer (BC) patients.

METHOD: A prospective, randomized, controlled clinical study including fifty individuals with a confirmed diagnosis of BC, individuals scheduled to receive DOX 60 mg/m2 in conjunction with Cyclophosphamide 600 mg/m2 (AC) for four courses at 21-day intervals. Both the control group and the ML group were randomly selected from the patient pool.

RESULTS: After treatment, a significant reduction in N-terminal Pro Brain Natriuretic Peptide (NT pro-BNP) levels was observed in the ML group compared to the control group (1756.0 [1054.0-2334.0] vs. 3788.0 [2226.0-4401.1] pg/mL, p < 0.001). Nuclear factor-kappa B (NF-κB) levels also decreased significantly in the ML group (2.23 [1.18-3.05] vs. 3.11 [2.39-3.25] pg/mL, p = 0.009). The median percentage reduction in Soluble suppression of tumorigenicity 2 (sST2) levels was more pronounced in the ML group (20.93 ± 5.45 ng/mL) than in the control group (24.16 ± 5.14 ng/mL, p = 0.036). Additionally, a strong positive correlation between NT pro-BNP and NF-κB levels was observed post-treatment (rs = 0.644, p < 0.001), supporting ML’s potential anti-inflammatory and cardioprotective effects.

CONCLUSION: The incorporation of ML into AC led to a substantial decrease in cardiac biomarkers confirming the feasibility of incorporating ML in individuals with breast cancer as an auxiliary treatment to prevent DOX-induced cardiotoxicity. Trial registration ClinicalTrials.gov: NCT05959889.

PMID:41034674 | DOI:10.1007/s00520-025-09947-z