Abstract
OBJECTIVES: To evaluate the effect of metformin on non-muscle-invasive bladder cancer (NMIBC) marker lesions. PATIENTS AND METHODS: A phase II, open-label, multicentre, marker lesion trial using oral metformin in patients with primary or recurrent, multiple, low-grade Ta-T1 NMIBC was conducted. After transurethral resection for histological confirmation, leaving one tumour as a marker lesion, 11 patients were treated with oral metformin up to 3000 mg per day for 3 months. Reported outcomes included response of the marker lesion, safety of metformin, quality of life and pharmacological and immunohistochemical examinations of the mechanism of action of metformin. RESULTS: One complete response and one partial response were observed. In the other nine patients, the marker lesion remained, while five of these patients also developed new Ta low-grade lesions. Diarrhoea grade ≤ 2 was the most common adverse event (AE), observed in nine out of 11 patients. No serious AEs related to study treatment occurred. Metformin concentrations in the urine were significantly higher than metformin levels in the blood. Immunohistochemical analysis before and after treatment showed no difference in expression of markers associated with the mechanism of metformin. CONCLUSION: We did not find conclusive evidence for the hypothesis of an antitumour effect of metformin in bladder cancer.