Metformin use and improved response to therapy in rectal cancer

Cancer Medicine

Heath D. Skinner¹  Christopher H. Crane¹  Christopher R. Garrett³  Cathy Eng³  George J. Chang⁴  John M. Skibber⁴  Miguel A. Rodriguez-Bigas⁴  Patrick Kelly¹  Vlad C. Sandulache²  Marc E. Delclos¹  Sunil Krishnan¹ 

[1] Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas;Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

关键词: Chemotherapy;    metformin;    radiation;    rectal cancer;   

DOI  :  10.1002/cam4.54

来源: Wiley

【 摘 要 】

Abstract

Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision (TME). Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy. In this study, we examined the effect of metformin use on pathologic complete response (pCR) rates and outcomes in rectal cancer. The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was 50.4 Gy (range 19.8–63). Nearly, all patients were treated with concurrent 5-fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%). Patients were categorized as nondiabetic (422), diabetic not taking metformin (40), or diabetic taking metformin (20). No significant differences between groups were found in clinical tumor classification, nodal classification, tumor distance from the anal verge or circumferential extent, pretreatment carcinoembryonic antigen level, or pathologic differentiation. pCR rates were 16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for diabetics taking metformin, with metformin users having significantly higher pCR rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P = 0.007). Metformin use was significantly associated with pCR rate on univariate (P = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking metformin had significantly increased disease-free (P = 0.013) and overall survival (P = 0.008) compared with other diabetic patients. Metformin use is associated with significantly higher pCR rates as well as improved survival. These promising data warrant further prospective study.

【 授权许可】

CC BY   
© 2013 The Authors. Cancer Medicine published by Blackwell Publishing Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.