The Effect of Metformin on Chemotherapy-Induced Toxicities in Non-diabetic Breast Cancer Patients: A Randomised Controlled Study

• Published in: Drug safety Vol. 46; no. 6; pp. 587 - 599
• Main Authors: Serageldin, Manar A., Kassem, Amira B., El-Kerm, Yasser, Helmy, Maged W., El-Mas, Mahmoud M., El-Bassiouny, Noha A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2023; Springer Nature B.V
• Subjects: Antidiabetics; Antineoplastic Agents - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Breastfeeding & lactation; Cancer therapies; Cardiotoxicity; Chemotherapy; Cyclophosphamide; Cyclophosphamide - adverse effects; Diabetes; Diabetes mellitus; Doxorubicin - adverse effects; Drug Safety and Pharmacovigilance; Echocardiography; Ejection fraction; Fatty liver; Female; Heart; Heart failure; Hematology; Humans; Kinases; Liver; Medical prognosis; Medicine; Medicine & Public Health; Metformin; Metformin - adverse effects; Mucositis; Neutropenia; Original; Original Research Article; Paclitaxel; Paclitaxel - adverse effects; Patients; Peripheral neuropathy; Pharmacology/Toxicology; Registration; Stroke Volume; Toxicity; Treatment Outcome; Ultrasonic imaging; Ventricle; Ventricular Function, Left; Egypt
• ISSN: 0114-5916; 1179-1942
• DOI: 10.1007/s40264-023-01305-4

Background and Objective Breast cancer patients treated with adriamycin-cyclophosphamide plus paclitaxel (AC-T) are often challenged with serious adverse effects for which no effective therapies are available. Here, we investigated whether metformin, an antidiabetic drug with additional pleiotropic effects could favourably offset AC-T induced toxicities. Patients and Methods Seventy non-diabetic breast cancer patients were randomised to receive either AC-T (adriamycin 60 mg/m 2 + cyclophosphamide 600 mg/m 2 × 4 cycles Q21 days, followed by weekly paclitaxel 80 mg/m 2 × 12 cycles) alone or AC-T plus metformin (1700 mg/day). Patients were assessed regularly after each cycle to record the incidence and severity of adverse events based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Moreover, baseline echocardiography and ultrasonography were done and repeated after the end of neoadjuvant therapy. Results Addition of metformin to AC-T resulted in significantly less incidence and severity of peripheral neuropathy, oral mucositis, and fatigue ( p < 0.05) compared to control arm. Moreover, the left ventricular ejection fraction (LVEF%) in the control arm dropped from a mean of 66.69 ± 4.57 to 62.2 ± 5.22% ( p = 0.0004) versus a preserved cardiac function in the metformin arm (64.87 ± 4.84 to 65.94 ± 3.44%, p = 0.2667). Furthermore, fatty liver incidence was significantly lower in metformin compared with control arm (8.33% vs 51.85%, p = 0.001). By contrast, haematological disturbances caused by AC-T were preserved after concurrent metformin administration ( p > 0.05). Conclusion Metformin offers a therapeutic opportunity for controlling toxicities caused by neoadjuvant chemotherapy in non-diabetic breast cancer patients. Trial Registration This randomised controlled trial was registered on November 20, 2019 in ClinicalTrials.gov under registration number: NCT04170465.