Pilot study of oral metformin in cancer-bearing cats

Abstract

A prospective dose escalation pilot study was performed in cancer-bearing cats to assess toxicity and surrogate biomarkers of pharmacologic activity of oral metformin hydrochloride. Nine cats with measurable spontaneous cancer were treated with oral metformin for 14 days. Monitoring included complete blood count (CBC), serum biochemistry, lactate, pH, insulin-like growth factor-1, and vascular endothelial growth factor serially until study completion. At the maximum tolerated dose of 10 mg kg^-1 q12 h side effects were primarily mild to moderate gastrointestinal upset (anorexia, vomiting, and/or weight loss). All cats developed a reduction in haematocrit. Six of nine cats developed new or progressive hyperlactatemia and one cat developed asymptomatic lactic acidosis. There were no clinical responders and two cats had modest measurable reduction in tumour size. In conclusion, we demonstrate potential pharmacologic activity of metformin at a clinically relevant dose and identify parameters for clinical monitoring and supportive care. Further investigation of metformin in cancer-bearing cats is warranted.

Keywords: dimethylbiguanine; feline; hyperlactatemia; lactic acidosis; neoplasms; oncology.