Reducing chemotherapy-induced toxicities in patients with breast cancer using anti-diabetes medication metformin.

This study investigated the beneficial effects of co-administering anti-diabetes medication metformin (Glucophage) and doxorubicin (Adriamycin)-cyclophosphamide (Cytoxan) with paclitaxel (Taxol) (AC-T) chemotherapy in non-diabetic patients with breast cancer (BC). The data showed that metformin reduced the occurrence and severity of toxicities associated with AC-T chemotherapy in patients with BC.

Breast cancer (BC) is a commonly occurring cancer of cells that make up breast tissue. It may be managed by chemotherapy. However, side effects can be serious, resulting in multiple toxicities. 

A drug combination offered to patients with BC is AC-T. A frequently reported side effect in patients treated with paclitaxel is peripheral nerve damage (paclitaxel-induced peripheral neuropathy; PIPN). AC-T treatment also causes inflamed, oral mucous membranes (oral mucositis) and fatigue. Doxorubicin can result in heart damage with subsequent heart failure. A fat build-up in the liver (fatty liver) may be a consequence of chemotherapy. Treatment options for controlling AC-T-induced toxicities remain limited.

Metformin is an oral medication used in patients with diabetes. It has been shown to reduce the risk of tumor spread, improve chemotherapy effectiveness, patient survival, and patient outcomes. Its actions are related to the effect on biochemical pathways through the activation of an enzyme called adenosine monophosphate-activated protein kinase (AMPK). However, it remains unclear whether metformin can minimize the occurrence of AC-T-induced toxicities in patients with BC.

This study included 70 patients with BC, without diabetes. Patients were randomly assigned to receive either AC-T alone or AC-T with metformin. Patients given AC-T with metformin, received AC-T with 850 mg of oral metformin, once-daily for a week, then twice-daily until 3 to 7 days before surgery. The occurrence and severity of treatment-related toxicities were recorded.

The addition of metformin to AC-T chemotherapy significantly reduced the occurrence and severity of PIPN, oral mucositis, and fatigue compared to AC-T alone. Heart function was maintained with AC-T and metformin treatment compared to AC-T chemotherapy alone. The occurrence of fatty liver disease was significantly reduced with the AC-T and metformin combined treatment.

This study concluded that the addition of metformin to AC-T chemotherapy can reduce the occurrence and severity of AC-T-induced toxicities in non-diabetic patients with BC.

In this study, patients knew which treatments they were receiving which might affect the conclusions.