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


CONCLUSIONS
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.
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.
Yousuke
Y
Nakai
Hiroyuki
H
Isayama
Takashi
T
Sasaki
Naminatsu
N
Takahara
Kei
K
Saito
Kazunaga
K
Ishigaki
Tsuyoshi
T
Hamada
Suguru
S
Mizuno
Koji
K
Miyabayashi
Keisuke
K
Yamamoto
Dai
D
Mohri
Hirofumi
H
Kogure
Natsuyo
N
Yamamoto
Hideaki
H
Ijichi
Keisuke
K
Tateishi
Minoru
M
Tada
Kazuhiko
K
Koike
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016016:Proportional Hazards Models; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine