5070 Background: Metformin is an inhibitor of the complex 1 in the respiratory chain, and is widely used in diabetes due to its effect on reducing insulin resistance. It has also been recently described to have effects via AMPK on inhibiting the mTOR kinase. Significant preclinical and epidemiological studies suggest its role in chemoprevention. These actions provide significant rationale to evaluate its utility in prostate cancer. Methods: Men were required to have histologically confirmed prostate cancer involving at least 20% of at least 1 unfragmented biopsy core. Exclusion criteria included patients who were found to be on treatment with any drug used for the treatment of any form of diabetes, or patients that began treatment for any form of diabetes during the course of the study. Pts were treated with up to 500mg tid of metformin. The primary objectives were to demonstrate safety and tolerability of neoadjuvant metformin administration in men with prostate cancer and to document changes in phospho-AKT signalling indices. Results: 24 patients were enrolled with 21 patients evaluable; median age was 64 yrs (range, 45-70 yrs). Baseline characteristics included median PSA 6 ng/mL (range, 3.22-36.11ng/mL). Median duration of drug treatment was 41 days (range 18-81). No grade 3 adverse events were reported during treatment or radical prostatectomy that were related to metformin. Significant pre-and post changes were noted in serum IGF1 (p=0.02), fasting glucose (p=0.03), BMI (p<0.01) and waist/hip ratio (p<0.01). There was a trend for a PSA reduction (p=0.08). There were no correlations between any metabolic, morphometric or cancer-related serum indices. On a per patient analyses, metformin reduced a computerised relative ki67 proliferation index by an average of 29% (absolute difference of 1.4%) compared to the baseline biopsy (p=0.006). P-4eBP1 staining was also reduced as assessed by H-score (p<0.01) consistent with the ability of metformin to inhibit mTOR. Conclusions: Neoadjuvant metformin is well tolerated prior to radical prostatectomy and shows promising effects on proliferation and signaling indices. Further research is needed to define the clinical utility of metformin in prostate cancer. Clinical trial information: NCT00881725.
A Case of Robot-Assisted Laparoscopic Radical Prostatectomy in Primary Small Cell Prostate Cancer
