Published online Nov 15, 2015. doi: 10.4291/wjgp.v6.i4.235
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
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.
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.