Retrospective Cohort Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2015; 6(4): 235-242
Published online Nov 15, 2015. doi: 10.4291/wjgp.v6.i4.235
Role of anti-stromal polypharmacy in increasing survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma
Samuel J Tingle, John A Moir, Steven A White
Samuel J Tingle, Faculty of Medical Sciences, Newcastle Medical School, Newcastle, Tyne and Wear NE2 4HH, United Kingdom
John A Moir, Newcastle Medical School Fibrosis Lab, Tyne and Wear NE2 4HH, United Kingdom
Steven A White, HPB and Transplant Consultant, HPB Unit, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear NE7 7DN, United Kingdom
Author contributions: Tingle SJ performed the research and wrote the paper; Moir JA and White SA supervised and designed the project.
Institutional review board statement: The study was reviewed and approved for publication by our institutional reviewer, NUTH trust.
Informed consent statement: All cases were anonymised during data collection therefore informed consent was not required.
Conflict-of-interest statement: No authors have any conflict of interest.
Data sharing statement: The original anonymised database is available for collaborative studies via the corresponding author, steven.white@nuth.nhs.uk.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Steven A White, Professor, HPB and Transplant Consultant, HPB Unit, Freeman Hospital, Freeman Road, Newcastle upon Tyne, Tyne and Wear NE7 7DN, United Kingdom. steven.white@nuth.nhs.uk
Telephone: +44-191-2137074
Received: June 2, 2015
Peer-review started: June 5, 2015
First decision: July 6, 2015
Revised: September 9, 2015
Accepted: October 16, 2015
Article in press: October 19, 2015
Published online: November 15, 2015
Processing time: 167 Days and 15.8 Hours
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Pancreatic ductal adenocarcinoma; Stroma; Polypharmacy; Calcium channel blockers; Angiotensin II receptor blockers; Angiotensin-converting enzyme inhibitors; Aspirin; Pancreaticoduodenectomy; Statins

Core tip: Stromal interactions play a large part in the dismal prognosis of pancreatic cancer. Recent laboratory studies have examined the potential use of common pharmaceuticals, such as calcium channel blocker (CCB), aspirin, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and statins, in inhibiting these protumorigenic stromal interactions. We retrospectively collected data from 164 patients whom underwent a pancreaticoduodenectomy to remove a pancreatic ductal adenocarcinoma, to see if the potential benefits of these drugs translated into increased survival. Our finding that those taking a combination of aspirin and CCB survived over twice as long as those on neither drug, highlights the potential of novel drug combinations to increase survival in pancreatic cancer.