title: Role of anti-stromal polypharmacy in increasing survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  To investigate the survival impact of common pharmaceuticals, which target stromal interactions, following a pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.
  
  
  METHODS
  Data was collected retrospectively for 164 patients who underwent a pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). Survival analysis was performed on patients receiving the following medications: angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB), calcium channel blockers (CCB), aspirin, and statins. Statistical analysis included Kaplan-meier survival estimates and cox multivariate regression; the latter of which allowed for any differences in a range of prognostic indicators between groups. Medications showing a significant survival benefit were investigated in combination with other medications to evaluate synergistic effects.
  
  
  RESULTS
  No survival benefit was observed with respect to ACEI/ARB (n = 41), aspirin or statins on individual drug analysis (n = 39). However, the entire CCB group (n = 26) showed a significant survival benefit on multivariate cox regression; hazard ratio (HR) of 0.475 (CI = 0.250-0.902, P = 0.023). Further analysis revealed that this was influenced by a group of patients who were taking aspirin in combination with CCB; median survival was significantly higher in the CCB + aspirin group (n = 15) compared with the group taking neither drug (n = 98); 1414 d vs 601 d (P = 0.029, log-rank test). Multivariate cox regression revealed neither aspirin nor CCB had a statistically significant impact on survival when given alone, however in combination the survival benefit was significant; HR = 0.332 (CI = 0.126-0.870, P = 0.025). None of the other medications showed a survival benefit in any combination.
  
  
  CONCLUSIONS
  Aspirin + CCB in combination appears to increase survival in patients with PDAC, highlighting the potential clinical use of combination therapy to target stromal interactions in pancreatic cancer.
authors.affiliation: Samuel J Tingle, Faculty of Medical Sciences, Newcastle Medical School, Newcastle, Tyne and Wear NE2 4HH, United Kingdom.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Tingle
authors.affiliation: Samuel J Tingle, Faculty of Medical Sciences, Newcastle Medical School, Newcastle, Tyne and Wear NE2 4HH, United Kingdom.
authors.forename: John A
authors.initials: JA
authors.lastname: Moir
authors.affiliation: Samuel J Tingle, Faculty of Medical Sciences, Newcastle Medical School, Newcastle, Tyne and Wear NE2 4HH, United Kingdom.
authors.forename: Steven A
authors.initials: SA
authors.lastname: White
keywords: Angiotensin II receptor blockers; Angiotensin-converting enzyme inhibitors; Aspirin; Calcium channel blockers; Pancreatic ductal adenocarcinoma; Pancreaticoduodenectomy; Polypharmacy; Statins; Stroma