Inhibition of renin–angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan.
British Journal of Cancer (Impact Factor: 4.84). 10/2010; 103(11):1644-8. DOI: 10.1038/sj.bjc.6605955
Source: PubMed


The renin-angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth.
We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs).
Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis.
The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

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Available from: Hideaki Ijichi, Sep 19, 2014
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    • "For example, Yamada et al. (2003) demonstrated that oral administration of candesartan (a widely used angiotensin II type-I receptor inhibitor) decreased ECM production and αSMA expression (activated PSC marker) in a rat chronic pancreatitis model. Furthermore, a retrospective clinical study suggested that pancreatic cancer patients treated with angiotensin II type 1 receptor inhibitors in combination with gemcitabine may have improved clinical outcome (Nakai et al., 2010). To expand on these findings the same authors recently completed a multicenter phase II clinical trial (35 patients with advanced pancreatic cancer) to examine whether patients treated with candesartan in combination with gemcitabine would have improved survival. "
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    • "Furthermore, angiotensin II-receptor blockers suppressed the cell proliferation effects of AT II in breast cancer cells.71 The addition of ACE inhibitors or angiotensin II-receptor blockers to platinum-based first-line chemotherapy contributed to prolonged survival in patients with advanced lung cancer72 and positively affected the prognosis of advanced pancreatic cancer patients receiving gemcitabine.73 RAS inhibitors also improved the outcome of sunitinib treatment in metastatic renal cell carcinoma.74 "
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    • "Wilop et al analysed retrospectively 287 patients with advanced non-small cell lung cancer undergoing first-line platinum-based chemotherapy, and reported that patients receiving either ACEIs or ARBs had a median survival that was 3.1 months longer than non-recipients (11.7 vs 8.6 months) (Wilop et al, 2009). Nakai et al reported the use of ACEIs or ARBs with gemcitabine was an independent prognostic factor for both progression-free survival and overall survival in 155 patients with advanced pancreatic cancer (Nakai et al, 2010). Two prospective studies suggested RAS inhibitor administration was effective as a salvage therapy in the treatment of prostate cancer and renal cell cancer (Uemura et al, 2005; Tatokoro et al, 2011). "
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