The inhibition of renin-angiotensin system in advanced pancreatic cancer: an exploratory analysis in 349 patients
The inhibition of renin-angiotensin system in advanced pancreatic cancer: an exploratory analysis in 349 patients
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DOI：
10.1007/s00432-014-1873-2
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发表时间：
2015-05-01
影响因子：
3.6
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
--
作者：
Nakai, Yousuke;Isayama, Hiroyuki;Koike, Kazuhiko
局部肾素-血管紧张素系统(RAS)作为胰腺癌治疗靶点的作用已被越来越多的报道，但在我们的前瞻性试验中，将血管紧张素系统抑制剂(ASIS)之一坎地沙坦加入吉西他滨并未显示出抗胰腺癌的活性。这项研究的目的是探索通过使用ASI抑制RAS而受益的亚组。对接受吉西他滨化疗的晚期胰腺癌连续患者进行回顾性研究。通过Cox比例风险模型估计总生存期(OS)和无进展生存期(PFS)的风险比(HR)。在2001至2013年间，349名晚期胰腺癌患者接受了以吉西他滨为基础的化疗；232名患者接受了转移治疗；210名患者接受了单一吉西他滨治疗；108名患者接受了ASIS治疗；166名从不吸烟的患者和188名糖尿病患者接受了治疗。中位PFS为4.9个月，OS为11.2个月。当使用ASIS的效果用Cox比例风险模型评估时，在PFS和OS中都有两个P交互作用的亚组：从不吸烟者和吉西他滨单用组。抑制RAS对PFS和OS的影响在不吸烟者分别为0.71(P=0.021)和0.68(P=0.014)，在接受吉西他滨单一治疗的患者中分别为0.70(P=0.027)和0.77(P=0.124)。
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.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.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.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.