Abstract 1434: Diabetic metastatic castration-resistant prostate cancer patients administered metformin during docetaxel chemotherapy have improved prostate cancer-specific and overall survival

Abstract

Abstract Introduction and Objective: Docetaxel (DTX) chemotherapy is currently one of the only treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). Although DTX treatment has been shown to provide survival benefits, it is not curative. Thus, there is a continued need to improve the therapeutic options available for mCRPC patients. One approach is combining DTX with other agents that enhance its effectiveness (i.e. chemosensitizers). Metformin, a commonly prescribed and well-tolerated oral biguanide used to treat type II diabetes, has been shown to exert anti-neoplastic effects in several types of solid tumors, including prostate cancer. More specifically, metformin has been shown to improve the efficacy of chemotherapy in breast cancer and colon cancer models. Niraula et al (2013) evaluated the effect of metformin combined with DTX in prostate cancer patients who participated in the TAX 327 trial. Metformin did not have a statistically significant additive or synergistic effect with docetaxel, but only 38 patients were included in the analysis. There is very limited data examining the combined effect of metformin and DTX in prostate cancer patients. Therefore, the objective of this study is to determine if diabetic mCRPC patients administered metformin during DTX treatment have improved prostate cancer-specific (PCa-specific) and overall survival (OS) when compared to nondiabetic mCRPC patients receiving DTX therapy. Methods: The primary objective of this retrospective study is to analyze patient data from the Ontario Cancer Registry (OCR), Ontario Diabetes Database (ODD), Canadian Institute for Health Information Discharge Abstract Database (CIHI DAD), National Ambulatory Care Reporting System (NACRS), Ontario Health Insurance Plan (OHIP), and the Registered Persons Database (RPDB) evaluate whether there is a difference in PCa-specific and OS between diabetic mCRPC patients administered metformin during DTX treatment and non-diabetic mCRPC patients receiving DTX treatment. The databases described previously are all accessible through the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada. Data has been collected and linked at ICES and a research-ready, anonymized dataset has been provided to our research group. Since receiving access to the dataset from ICES, statistical analysis (including multivariate Cox proportional hazards regression, logrank test, and Kaplan Meier survival curves) is in progress using SAS software. Results and Conclusions: Data analysis is currently in progress. If metformin is shown to have a chemosensitizing effect in diabetic mCRPC patients, this would indicate a novel therapeutic approach that is needed for this patient population. Citation Format: Michelle Mayer, Laurence Klotz, Vasundara Venkateswaran. Diabetic metastatic castration-resistant prostate cancer patients administered metformin during docetaxel chemotherapy have improved prostate cancer-specific and overall survival. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1434.