Update on androgen deprivation therapy and adjuvant metformin (ADMET) trial for men with treatment naïve metastatic prostate cancer

Objective - To determine the prognostic and metabolic benefits of metformin in those starting androgen deprivation therapy (ADT) for newly diagnosed metastatic prostate cancer. Methods - Androgen deprivation therapy and adjuvant metformin (ADMET) trial is a single blinded, multi-site (Princess Alexandra Hospital, Gold Coast Hospital, Epworth Healthcare Centre), randomized, placebo controlled, 2-year, prospective clinical trial. The study has been open for recruitment since September 2014. In total, 80 patients with metastatic prostate cancer who are commenced on ADT are expected to be recruited. Patients are re- viewed every 6–12 weeks (site specific) for the assessment of physical and serum measurements, and circulating tumor cells (CTCs). Results - In the last 14 months, sixty patients have been screened and 25 patients recruited into the clinical trial. Thirteen patients were diagnosed with metabolic syndrome and five with diabetes at the time of starting ADT. At screening, 21 of 25 patients demonstrated circulating tumour cells with the mean number of 780 (range 1–4750, ± 1140). At 3 months, 20 patients were available for comparative analysis. Patients demonstrated significant changes (%)inweight(0.45 ± 2.21), prostate-specific antigen ( − 92.33 ± 5.25), total cholesterol (8.54 ± 18.24), triglyceride (11.01 ± 34.23), high density lipopro- tein (15.32 ± 28.31), low-density lipoprotein (12.58 ± 20.86), fasting glu- cose 0.84 ± 20.12), fasting insulin (12.23 ± 99.21) and homeostatic model assessment-insulin resistance score (19.12 ± 85.82). Unexpectedly, the num- ber of CTCs increased at 12–24 weeks in most patients after uniform decline in number at 6 weeks. Conclusions - Although ADT remains a core component of treating men with metastatic prostate cancer, it is associated with metabolic syndrome and associated morbidities such as cardiovascular disease and diabetes. At the conclu- sion of this clinical trial, we aim to determine whether metformin has a role in minimizing the risk of metabolic aberration caused by ADT and if prognostic benefit could result from the therapy.