The Potential Synergistic Effects of Metformin and Enzalutamide in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Objective: The primary objective is to investigate the potential synergistic effects of concurrent metformin administration alongside enzalutamide therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).The study aims to uncover novel mechanisms that could lead to enhanced treatment outcomes, including more durable responses, delayed disease progression, and prolonged survival.This exploration seeks to provide critical insights that could expand the therapeutic options available for mCRPC patients.Methods: This retrospective study evaluated the impact of metformin on progression-free survival (PFS) in 92 patients with mCRPC who received second-line enzalutamide.Patients were divided into two groups: 65 Received enzalutamide alone, while 27 were treated with both enzalutamide and metformin.The primary endpoint was PFS.Statistical analyses, including Kaplan-Meier survival analysis and log-rank tests, were used to compare PFS between the two cohorts, aiming to assess the benefits of metformin in this treatment context. Results:The analysis revealed that the mean survival time for the enzalutamide-only group was 23 months, while the mean for the enzalutamide-plus-metformin group was 18 months.However, the log-rank test showed no statistically significant difference between the two groups, suggesting that these trends may not indicate a true difference in treatment effectiveness.The median survival times were both 12 months for each treatment cohort, further emphasizing the lack of significant improvement in progression-free survival with the addition of metformin. Conclusion:This retrospective study explored the effects of adding metformin to enzalutamide therapy in patients with mCRPC after docetaxel treatment.Although mean survival times suggested a potential benefit for the combination, statistical analysis revealed no significant differences in median survival between the two groups.These findings may be influenced by biases inherent in the retrospective design and the small sample size.Thus, further research with larger cohorts and longer follow-up is needed to rigorously evaluate the benefits of the metformin-enzalutamide combination in managing mCRPC.