title: Metformin Use and Outcome of Sunitinib Treatment in Patients With Diabetes and Metastatic Renal Cell Carcinoma.
abstract: Although studies in several cancer types suggest that metformin has antitumor activity, its effect on the outcome of targeted therapies in metastatic renal cell carcinoma (mRCC) is poorly defined. We aimed to analyze the effect of metformin use on the outcome of sunitinib treatment in diabetic patients with mRCC.
  
  
  
  We performed a retrospective study of diabetic patients with mRCC, who were treated with sunitinib in 8 centers across 2 countries. Patients were divided into metformin users and nonusers. The effect of metformin use on response rate, progression-free survival (PFS), and overall survival (OS), was tested. Furthermore, univariate and multivariate analyses of the association between clinicopathologic factors and metformin use, and outcome were performed using the entire patient cohort.
  
  
  
  Between 2004 and 2014, 108 diabetic patients with mRCC were treated with sunitinib. There were 52 metformin users (group 1) and 56 nonusers (group 2). The groups were balanced regarding clinicopathologic factors. Clinical benefit (partial response + stable disease) in group 1 versus 2 was 96% versus 84% (P = .054). Median PFS was 15 versus 11.5 months (P = .1). Median OS was 32 versus 21 months (P = .001). In multivariate analyses of the entire patient cohort (n = 108), factors associated with PFS were active smoking and pretreatment neutrophil to lymphocyte ratio > 3. Factors associated with OS were metformin use (hazard ratio, 0.21; P < .0001), Heng risk, active smoking, liver metastases, and pretreatment neutrophil to lymphocyte ratio > 3.
  
  
  
  Metformin might improve the OS of diabetic patients with mRCC who are treated with sunitinib.
authors.affiliation: Department of Oncology, Meir Medical Center, Kfar Saba, Israel. Electronic address: danielkeizman@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Keizman
authors.affiliation: Department of Oncology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Ish-Shalom
authors.affiliation: Department of Oncology, Asaf Harofe Medical Center, Zerifin, Israel.
authors.forename: Avishay
authors.initials: A
authors.lastname: Sella
authors.affiliation: Department of Oncology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Gottfried
authors.affiliation: Department of Oncology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Maimon
authors.affiliation: Department of Oncology, Rambam Medical Center, Haifa, Israel.
authors.forename: Avivit
authors.initials: A
authors.lastname: Peer
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
authors.forename: Hans
authors.initials: H
authors.lastname: Hammers
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sinibaldi
authors.affiliation: Department of Oncology, Rabin Medical Center, Petach-Tikva, Israel.
authors.forename: Victoria
authors.initials: V
authors.lastname: Neiman
authors.affiliation: Department of Oncology, Rabin Medical Center, Petach-Tikva, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Rosenbaum
authors.affiliation: Department of Oncology, Tel Aviv Sourasky Medical center, Tel Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Sarid
authors.affiliation: Department of Oncology, Soroka Medical Center, Beer-Sheva, Israel.
authors.forename: Wilmosh
authors.initials: W
authors.lastname: Mermershtain
authors.affiliation: Department of Oncology, Soroka Medical Center, Beer-Sheva, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Rouvinov
authors.affiliation: Department of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Raanan
authors.initials: R
authors.lastname: Berger
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D011758:Pyrroles; D008687:Metformin; D000077210:Sunitinib
keywords: Metastatic Renal Cell Carcinoma; Metformin; Outcome; Sunitinib