title: Angiotensin II type-1 receptor blockers enhance the effects of bevacizumab-based chemotherapy in metastatic colorectal cancer patients.
abstract: The local renin-angiotensin system promotes angiogenesis and vascular proliferation via expression of vascular endothelial growth factor or epidermal growth factor receptor. We hypothesized that angiotensin II type-1 receptor blockers (ARBs) in combination with bevacizumab (Bev) may improve clinical outcomes in patients with metastatic colorectal cancer (mCRC). A total of 181 patients with histopathologically confirmed mCRC treated with first-line oxaliplatin-based chemotherapy in combination with Bev were enrolled between June, 2007 and September, 2010. The patients were divided into two groups based on the presence or absence of treatment with ARBs prior to the initiation of second-line chemotherapy. Kaplan-Meier analysis and Cox proportional hazard modeling were used in the statistical analysis. The median progression-free survival (PFS) in patients undergoing second-line chemotherapy in combination with Bev and ARBs (n=56) vs. those treated in the absence of ARBs (n=33) was 8.3 vs. 5.7 months, respectively [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.35-0.94, P=0.028]. The median overall survival (OS) was 26.5 vs. 15.2 months, respectively (HR=0.47, 95% CI: 0.25-0.88, P=0.019). In the multivariate analysis, the use of ARBs was independently associated with prolongation of OS and PFS. In conclusion, the use of ARBs prolonged survival in mCRC patients.
authors.affiliation: Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Osumi
authors.affiliation: Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsusaka
authors.affiliation: Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Wakatsuki
authors.affiliation: Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.affiliation: Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Eiij
authors.initials: E
authors.lastname: Shinozaki
authors.affiliation: Department of Gastroenterology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
keywords: angiogenesis; angiotensin II type-1 receptor blockers; bevacizumab; vascular endothelial growth factor