Efficacy of metformin treatment for bitches with the mammary gland carcinoma

Abstract

The relevance of improvement and clinical approval of modern treatment regimens is determined by the insufficient efficiency of protocols for the treatment of malignant tumors in dogs and the lack of research on the possibility of repurposing certain pharmacological agents for use in veterinary oncology. The manuscript demonstrates the results of a pilot study of using metformin as part of a chemotherapy protocol in female dogs with poorly differentiated tubular mammary carcinoma after mastectomy. Considering the hypoglycemic effect of metformin, it was used as part of an adjuvant protocol in a metronomic mode in female dogs with a normal and high body mass index. Combined oral administration of cyclophosphamide (endoxan) and metformin at a dose of 12.5 mg/m 2 and 10 mg/kg, respectively, for 6 months prolonged the median survival in female dogs with a normal body index (from 135.8 days, 95% CI 40-234 to 178.6 days, 95% CI 22-394, p < 0.01) as well as in overweight patients (from 93.4 days, 95% CI 15-174 to 237.8 days, 95% CI 38-373, p < 0.001). Herewith, a high body mass index compared to a normal one recognized as the risk of animal death due to the disease progression. The feasibility of using metformin in overweight patients is consistent with a reliably high glucose level before starting treatment. Herewith, blood content of triglycerides and total cholesterol did not depend on the body weight of the dogs and was within the physiological norm in all dogs. Adjuvant therapy with cyclophosphamide (endoxan) and metformin in a metronomic mode for six months was accompanied by a slight decrease (within the lower limit of reference values) of the blood glucose level against the background of the absence of pronounced changes in the concentration of triglycerides and total cholesterol. Improved long-term prognosis and the insignificant risk of side effects allow recommending metronomic therapy with cyclophosphamide (endoxan) and metformin after mastectomy in female dogs with mammary gland carcinoma.