|作者：||Rana R. McKay, Gustavo E. Rodriguez, Xun Lin, Marina D. Kaymakcalan, Ole-Petter R. Hamnvik, Venkata S. Sabbisetti, Rupal S. Bhatt, Ronit Simantov, Toni K. Choueiri|
11Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
22Pfizer Oncology, Pfizer Inc., New York, New York.
33Division of Endocrinology, Diabetes, and Hypertension, Brigham and Woman's Hospital, Boston, Massachusetts.
44Department of Pharmacy and Clinical Support, Dana-Farber Cancer Institute, Boston, Massachusetts.
55Department of Nephrology, Brigham and Woman's Hospital, Boston, Massachusetts.
66Division of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
|刊名：||Clinical Cancer Research, 2015, Vol.21 (11), pp.2471-2479|
|来源数据库：||Duke University Press|
|原始语种摘要：||Purpose: The renin-angiotensin system may play a role in carcinogenesis. The purpose of this study was to evaluate the impact of angiotensin system inhibitors (ASI) on outcomes in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era.Experimental Design: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan–Meier method.Results: A total of 4,736 patients were included, of whom 1,487 received ASIs and 783 received other antihypertensive agents. Overall, ASI users demonstrated improved overall survival (OS) compared with users of other antihypertensive agents (adjusted HR, 0.838, P = 0.0105, 26.68 vs. 18.07 months) and... individuals receiving no antihypertensive therapy (adjusted HR, 0.810, P = 0.0026, 26.68 vs. 16.72 months). When stratified by therapy type, a benefit in OS was demonstrated in ASI users compared with nonusers in individuals receiving VEGF therapy (adjusted HR, 0.737, P < 0.0001, 31.12 vs. 21.94 months) but not temsirolimus or IFNα. An in vitro cell viability assay demonstrated that sunitinib in combination with an ASI significantly decreased RCC cell viability compared with control at physiologically relevant doses. This effect was not observed with either agent alone or with other non-ASI antihypertensives or temsirolimus.Conclusions: In the largest analysis to date, we demonstrate that ASI use improved survival in mRCC patients treated in the targeted therapy era. Further studies are warranted to investigate the mechanism underlying this interaction and verify our observations to inform clinical practice. Clin Cancer Res; 21(11); 2471–9. ©2015 AACR.|