Androgen deprivation therapy (ADT) remains the mainstay of treatment for men with biochemical relapse after definitive treatment where no further local therapy is appropriate. The timing of initiation is critical as ADT impacts on quality of life and is associated with increased non-prostate cancer mortality. Metformin and statin are widely used medications with well-known safety profiles and have demonstrated activity in prostate cancer in pre-clinical and observational studies. The objective of this study is to determine whether metformin/statin can induce a prostate-specific antigen (PSA) response and/or alter its kinetics in men with BCRPC.
Method:
In this single-centre retrospective review we identified patients with BCRPC treated with metformin and/or statin between January 2016 and 2018. All patients had not yet initiated ADT for BCRPC. De-identified demographic and clinical information were obtained through review of electronic medical records. The primary outcome was PSA response defined as ≤30% of baseline.
Results:
A total of 31 patients were included. All treatments were initiated due to patients’ desire to delay/avoid ADT initiation. The median age was 72 years, with the majority (75%) having received radical prostatectomy and salvage radiotherapy as their definitive treatments. Existing history of diabetes mellitus and hypercholesterolaemia was present in 7% and 23% of patients, respectively. Twenty-seven patients (87%) received both metformin and statin. PSA response was observed in five (16%) patients. Median duration on treatment was 8 months. Mean PSA doubling time was significantly longer after initiation of treatment with metformin/statin compared to baseline (26.8 vs. 8.6 months, p=0.001). Treatment was well-tolerated with grade 1 diarrhoea being the most common adverse event.
Conclusion:
Metformin/statin use is associated with PSA response and slower PSA velocity in men with BCRPC. A prospective study is warranted to confirm its efficacy and clinical utility in delaying ADT initiation.