Metformin Alleviates Chemotherapy-Induced Toxicities in Non-Diabetic Breast Cancer Patients: A Randomized Controlled Study

Abstract

<b>Abstract ID 15990</b> <b>Poster Board 247</b> 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 favorably offset AC-T induced toxicities. Seventy non-diabetic breast cancer patients were randomized to receive either AC-T (adriamycin 60 mg/m²+ cyclophosphamide 600 mg/m² X 4 cycles Q21 days, followed by weekly paclitaxel 80 mg/m²X 12 cycles) alone or AC-T plus metformin (1700 mg/d). Patients were interviewed 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. The addition of metformin to AC-T resulted in significantly less incidence and severity of peripheral neuropathy, oral mucositis, and fatigue (p &lt;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% versus 51.85%, p= 0.001). By contrast, hematological disturbances caused by AC-T were preserved after concurrent metformin administration (p&gt; 0.05). In conclusion. Metformin offers a therapeutic opportunity for controlling toxicities caused by neoadjuvant chemotherapy in non-diabetic breast cancer patients.