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

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/m2 + cyclophosphamide 600 mg/m2 × 4 cycles Q21 days, followed by weekly paclitaxel 80 mg/m2 × 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). 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.