الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Background: There is a growing evidence of antineoplastic properties of metformin (MET) in prostate cancer. Many retrospective studies suggested that using MET was associated with reduction of biochemical recurrence and improvement in overall survival among prostate cancer patients. Furthermore, it was reported that MET was associated with reduction of risk of development of castration-resistant prostate cancer (CRPC). Hereby, this randomized controlled trial evaluated the role of MET among men with high-risk locally advanced or hormone sensitive metastatic prostate cancer (m HSPC). Aim of the study: to assess the impact of metformin on the time to progression to castrate resistant prostate cancer. Methods: This is a randomized single-blinded controlled trial. Eligible patients were high risk localized or mHSPC. Patients were randomly allocated to receive either standard of care (SOC) alone; androgen deprivation and bicalutamide 50mg or (SOC) plus metformin (850 mg twice daily). The primary endpoint was time to CRPC. The secondary endpoint was overall survival (OS) and PSA response rate. The trial was registered at ClinicalTrials.gov ID NCT03137186. Results: Eligible patients (n: 124) were randomly allocated to 62 in MET arm and 62 patients in the SOC arm. The baseline demographic and disease characteristics were comparable between the two arms. Over a median follow up of 18 months, there were 13 deaths in the MET arm versus 18 deaths in the control arm (P=0.2). The median time to CRPC was longer in MET arm 29 months (95%CI 25-33) compared to the control arm 20 months (95%CI 16-24) (P=0.01). After subgroup analysis, the median time to progression to CRPC was longer at MET arm in high risk localized prostate cancer (P=0.02), in mHSPC patients with low tumor volume the difference was of borderline significance (P= 0.06), and in those with node positive (N1) disease was highly significant (P=0.001). While in patients with high tumor volume, there was no significant difference regarding the median time to CRPC among the two groups (P=0.9). Regarding secondary objective, there was no significant difference between two arms in overall survival (OS) (P= 0.1) or PSA response rate (P=0.5). Notably no significant adverse events were reported in MET arm apart of self-limiting diarrhea. Conclusions: According to our data, metformin potentially prolongs the time to CRPC in locally advanced and metastatic prostate cancer patients when combined with ADT especially in those with high risk localized prostate cancer, clinically node positive and in those with low tumor volume metastatic hormone naive patients.