Angiotensin II type-1 receptor blockers enhance the effects of bevacizumab-based chemotherapy in metastatic colorectal cancer patients

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...

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Bibliographic Details
Published in:Molecular and clinical oncology 2015-11, Vol.3 (6), p.1295-1300
Main Authors: OSUMI, HIROKI, MATSUSAKA, SATOSHI, WAKATSUKI, TAKERU, SUENAGA, MITSUKUNI, SHINOZAKI, EIIJ, MIZUNUMA, NOBUYUKI
Format: Article
Language:English
Subjects:
Age
Angiogenesis
Angiotensin II receptor blockers
angiotensin II type-1 receptor blockers
bevacizumab
Chemotherapy
Clinical outcomes
Colorectal cancer
Confidence intervals
Disease control
Drug therapy
Gender
Health aspects
Hypertension
Immunotherapy
Liver
Lymphatic system
Medical prognosis
Metastasis
Monoclonal antibodies
Multivariate analysis
Oncology
Pancreatic cancer
Patients
Rodents
Targeted cancer therapy
Tumors
Vascular endothelial growth factor
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Summary: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.
ISSN:2049-9450
2049-9469
DOI:10.3892/mco.2015.630