title: The Effect of Metformin Use during Docetaxel Chemotherapy on Prostate Cancer Specific and Overall Survival of Diabetic Patients with Castration Resistant Prostate Cancer.
abstract: Docetaxel is the first line chemotherapy currently used to treat patients with symptomatic metastatic castration resistant prostate cancer. Although it provides survival benefits, it is associated with significant side effects. Novel therapeutic options are needed for patients with metastatic castration resistant prostate cancer and an approach is combining docetaxel with chemosensitizing agents. Metformin has been shown to improve the survival of patients with breast, lung and endometrial cancer receiving chemotherapy, and enhance chemotherapeutic efficacy in breast cancer and colon cancer cells. However, to our knowledge the chemosensitizing effect of metformin in prostate cancer has not been explored. Therefore, the hypothesis for our study was that diabetic patients with metastatic castration resistant prostate cancer who were administered metformin during docetaxel chemotherapy would have improved prostate cancer specific and overall survival.
  
  
  
  This retrospective cohort study used data from several Ontario administrative health care databases. Men older than 65 years diagnosed with metastatic castration resistant prostate cancer and treated with docetaxel were stratified into groups based on diabetes status and use of antidiabetic medications. We evaluated the effect of metformin use with docetaxel on prostate cancer specific survival and overall survival using Kaplan-Meier survival curves, the log rank test and multivariate Cox proportional HRs.
  
  
  
  Survival curves showed that metformin use with docetaxel did not improve prostate cancer specific survival (p = 0.9562) or overall survival (p = 0.9927). HRs showed no significant effect of metformin use with docetaxel on prostate cancer specific survival (HR = 0.96, p = 0.66) or overall survival (HR = 0.94, p = 0.39).
  
  
  
  Metformin use during docetaxel chemotherapy did not significantly improve prostate cancer specific or overall survival in diabetic patients with metastatic castration resistant prostate cancer. This study indicates that metformin may not be an effective chemosensitizer for metastatic castration resistant prostate cancer.
authors.affiliation: Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Mayer
authors.affiliation: Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Klotz
authors.affiliation: Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: vasundara.venkateswaran@sunnybrook.ca.
authors.forename: Vasundara
authors.initials: V
authors.lastname: Venkateswaran
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000188:drug therapy* / Q000401:mortality*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D000077143:Docetaxel / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D000077143:Docetaxel; D008687:Metformin
keywords: castration-resistant; diabetes mellitus; docetaxel; metformin; mortality; prostatic neoplasms