3237 - Hormone Changes Associated with Metformin Treatment in Prostate Cancer Patients Initiating Androgen Deprivation Therapy: A Correlative Analysis of the PRIME Study
Presenter(s)
M. T. Gorman1, N. H. Usmani1, M. Pollak2, Y. Wang3, S. Ghosh1,4, A. Elangovan5, J. Kim6, J. Thoms7, M. Bouchard8, M. Peacock9,10, N. E. Fleshner11, H. Campbell12, E. Vigneault13, F. Vincent14, A. So9,10, F. L. Cury15, H. C. Quon16, R. G. Carlson Jr17, C. Lambert18, and B. J. Eigl9,10; 1University of Alberta, Edmonton, AB, Canada, 2Departments of Medicine and Oncology, McGill University, Montreal, QC, Canada, 3Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada, 4Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, 5Saskatoon Cancer Centre, Saskatoon, SK, Canada, 6Department of Radiation Oncology, CancerCare Manitoba, Winnipeg, MB, Canada, 7Dr. H. Bliss Murphy Cancer Centre, St. John's, NF, Canada, 8Centre Intégré Universitaire de Santé et de Services Sociaux de L' Estrie-Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada, 9BC Cancer – Vancouver Center, Vancouver, BC, Canada, 10University of British Columbia, Vancouver, BC, Canada, 11University of Toronto, Toronto, ON, Canada, 12Dalhousie University, Halifax, NS, Canada, 13Centre de recherche du CHU de Québec, Quebec City, QC, Canada, 14Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec, Trois-Rivières, QC, Canada, 15McGill University Health Centre, Montreal, QC, Canada, 16Division of Radiation Oncology, Arthur J.E Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada, 17Shirley and Jim Fielding Northeast Cancer Centre, Sudbury, ON, Canada, 18Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada
Purpose/Objective(s):
To determine if prostate cancer (PCa) patients (pts) receiving androgen deprivation therapy (ADT) will have predictable changes in laboratory biomarkers associated with metabolic syndrome and type II diabetes that can be mitigated with metformin.Materials/Methods:
PRIME is phase III multicenter double-blind, randomized controlled trial in which 166 normoglycemic pts with PCa receiving at least 9 months ADT were randomized 2:1 to receive metformin 850 mg or placebo BID orally for 18 months. For this correlative analysis, 47 pts from the metformin arm and 32 pts from the placebo arm underwent optional serum collection and analysis. Fasting (F) and post-prandial (PP) serum samples of the following analytes were collected at baseline, 9, and 12 months: IGF, IGFBP1, IGFBP2, IGFBP3, IGFBP7, leptin, adiponectin, GDF15, insulin, C-peptide, GIP, GLP-1, and IL-6. Two-tailed paired t-tests were used to determine if significant changes in laboratory values were evident in pts receiving metformin vs. placebo. Paired t-tests were conducted to evaluate analyte changes between timepoints for the metformin and placebo groups separately.Results:
Mean leptin values increased markedly in the placebo group and significantly less in the metformin group across all time points. Mean IGFBP1 values increased more with metformin compared to placebo at all time-points. Mean IL-6 values decreased with metformin compared to placebo at all time points (Table 1). C-peptide and GLP-1 showed significant changes with metformin vs. placebo only at 9-months F (p<0.05). Insignificant trends in mean changes were observed with various analytes. In the placebo group, leptin, GDF15, and IGFBP3 significantly increased across all time points compared to baseline with ADT alone (p<0.05). Other metabolites showed significant changes only at certain time points compared to baseline with ADT alone.Conclusion:
This study demonstrates that metformin can mitigate adverse changes induced by ADT in biomarkers (leptin, IGFBP1, IL-6) associated with an increased risk of type 2 diabetes and metabolic syndrome. We also demonstrate an association with ADT treatment and unfavorable changes in specific metabolites associated with metabolic syndrome. Additionally, the attenuated increase in leptin with metformin signals a potential for improved PCa outcomes, as high leptin values have been correlated with aggressive disease and worse prognosis. Abstract 3237 - Table 1| 9 months F | 12 months F | 9 months PP | 12 months PP | ||
| Leptin, pg/mL | Placebo | +9629.56 | +12247.69 | +9990.28 | +9959.69 |
| Metformin | +2284.28 | +4231.47 | +2153.09 | +2952.23 | |
| p-value | 4.98x10-5 | 2.57x10-4 | 5.37x10-6 | 4.02x10-4 | |
| IGFBP1, ng/mL | Placebo | -0.21 | +0.44 | -0.20 | +0.08 |
| Metformin | +0.76 | +1.66 | +0.53 | +1.00 | |
| p-value | 0.03 | 0.03 | 0.04 | 0.05 | |
| IL-6, pg/mL | Placebo | +2.07 | +1.20 | +1.82 | +0.79 |
| Metformin | -1.14 | -1.53 | -1.39 | -1.73 | |
| p-value | 0.06 | 0.02 | 0.04 | 0.03 |