The inhibition of renin-angiotensin system in advanced pancreatic cancer: an exploratory analysis in 349 patients.

Abstract

PURPOSE:

The role of local renin-angiotensin system (RAS) as a target for the treatment of pancreatic cancer has been increasingly reported, but the addition of candesartan, one of angiotensin system inhibitors (ASIs), to gemcitabine in our prospective trial failed to demonstrate activity against pancreatic cancer. The aim of this study was to explore subgroups that would benefit from the inhibition of RAS by the use of ASIs.

METHODS:

Consecutive patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy were retrospectively studied. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated by a Cox proportional hazards model. Interactions between the use of ASIs and each subgroup were tested.

RESULTS:

Between 2001 and 2013, 349 patients received gemcitabine-based chemotherapy for advanced pancreatic cancer; 232 were metastatic, 210 received gemcitabine monotherapy, 108 took ASIs, 166 were never smokers and 188 were diabetic. The median PFS and OS were 4.9 and 11.2 months, respectively. When the effects of the use of ASIs were evaluated by a Cox proportional hazard model, there were two subgroups with P interaction <0.10 both in PFS and OS: never smokers and gemcitabine monotherapy. HRs for PFS and OS by the inhibition of RAS were 0.71 (P = 0.021) and 0.68 (P = 0.014) in never smokers and 0.70 (P = 0.027) and 0.77 (P = 0.124) in patients receiving gemcitabine monotherapy.

CONCLUSION:

The inhibition of RAS in advanced pancreatic cancer might improve clinical outcomes in cases without a history of smoking or in cases receiving gemcitabine monotherapy.

• Authors: Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Naminatsu Takahara, Kei Saito, Kazunaga Ishigaki, Tsuyoshi Hamada, Suguru Mizuno, Koji Miyabayashi, Keisuke Yamamoto, Dai Mohri, Hirofumi Kogure, Natsuyo Yamamoto, Hideaki Ijichi, Keisuke Tateishi, Minoru Tada, Kazuhiko Koike
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 141 Issue 5 Pg. 933-9 (May 2015) ISSN: 1432-1335 [Electronic] Germany
• PMID: 25398651 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Deoxycytidine
• Gemcitabine

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Female
• Humans
• Male
• Middle Aged
• Odds Ratio
• Pancreatic Neoplasms (diagnostic imaging, drug therapy, metabolism, pathology)
• Proportional Hazards Models
• Renin-Angiotensin System (drug effects)
• Retrospective Studies
• Tomography, X-Ray Computed
• Treatment Outcome
• Gemcitabine