title: Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies.
abstract: OBJECTIVE
  To evaluate whether statin use influences gastrointestinal cancer prognosis in patients with diabetes mellitus (DM).
  
  
  METHODS
  We reviewed all DM patients diagnosed at Roswell Park Cancer Institute with emergent gastrointestinal malignancy (January 2003 to December 2010) (N = 222). Baseline demographic, clinical history, and cancer outcomes were documented. Overall survival (OS) and disease-free survival (DFS) comparisons across various treatment groups were assessed by Kaplan-Meier and Cox proportional hazards.
  
  
  RESULTS
  Use of statin, alone or in combination, was associated with improved OS and DFS (hazard ratio [HR] = 0.65, P = .06; HR = 0.60, P < .02). We report similar OS and DFS advantage among users of mono- or combined metformin therapy (HR = 0.55, P < .01; HR = 0.63, P < .02). Concomitant use of metformin and statin provided a synergistic OS and DFS benefit (HR = 0.42, P < .01; HR = 0.44, P < .01). Despite significant tobacco and alcohol use history, patients with upper gastrointestinal cancers derived enhanced cancer outcomes from this combination (HR = 0.34, P < .01; HR = 0.43, P < .02), while receiving a statin without metformin or metformin without a statin did not provide significant cancer-related benefits.
  
  
  CONCLUSIONS
  Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
authors.affiliation: 1 Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.|2 Pharmacy Service, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: George K
authors.initials: GK
authors.lastname: Nimako
authors.affiliation: 1 Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.|2 Pharmacy Service, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Zachary A P
authors.initials: ZA
authors.lastname: Wintrob
authors.affiliation: 1 Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Dmitriy A
authors.initials: DA
authors.lastname: Sulik
authors.affiliation: 1 Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Donato
authors.affiliation: 1 Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.|2 Pharmacy Service, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Ceacareanu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000401:mortality*; D018572:Disease-Free Survival; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: cancer outcomes; gastrointestinal malignancies; metformin; statin; synergistic effect