The effects of nonspecific HIF1α inhibitors on development of castrate resistance and metastases in prostate cancer. (27th January 2014)

• Record Type: Journal Article
• Authors: Ranasinghe, Weranja K. B.; Sengupta, Shomik; Williams, Scott; Chang, Mike; Shulkes, Arthur; Bolton, Damien M.; Baldwin, Graham; Patel, Oneel
• Is Part Of: Cancer medicine. Volume 3:Number 2(2014:Apr.)
• Page Start: 245
• Page End: 251
• Publication Date: 2014-01-27
• Subjects: 616.994005
• DOI: 10.1002/cam4.189
• Languages: English
• ISSNs: 2045-7634

Abstract

<abstract abstract-type="main" id="cam4189-abs-0001"> <title>Abstract</title> <p>Expression of hypoxia‐inducible factor (HIF)1<italic>α</italic> increases the risk of castrate‐resistant prostate cancer (CRPC) and metastases in patients on androgen deprivation therapy (ADT) for prostate cancer (PC). We aimed to investigate the effects of nonspecific HIF1<italic>α</italic> inhibitors (Digoxin, metformin, and angiotensin‐2 receptor blockers) on development of CRPC and metastases while on ADT. A retrospective review of prospectively collected medical records was conducted of all men who had continuous ADT as first‐line therapy for CRPC at the Austin Hospital from 1983 to 2011. Association between HIF1<italic>α</italic> inhibitor medications and time to develop CRPC was investigated using actuarial statistics. Ninety‐eight patients meeting the criteria were identified. Eighteen patients (21.4%) were treated with the nonspecific HIF1<italic>α</italic> inhibitors. Both groups had similar characteristics, apart from patients on HIF1<italic>α</italic> inhibitors being older (70 years vs. 63.9 years). The median CRPC‐free survival was longer in men using HIF1<italic>α</italic> inhibitors compared to those not on inhibitors (6.7 years vs. 2.7 years, <italic>P</italic> = 0.01) and there was a 71% reduction in the risk of developing CRPC (HR 0.29 [95% CI 0.10–0.78] <italic>P</italic> = 0.02) after adjustment for Gleason score, age, and prostate‐specific antigen (PSA). The median metastasis‐free survival in men on HIF1<italic>α</italic> inhibitors was also significantly longer compared to those on no inhibitors (5.1 years vs. 2.6 years, <italic>P</italic> = 0.01) with an 81% reduction in the risk of developing metastases (HR 0.19 [CI 0.05–0.76] <italic>P</italic> = 0.02) after adjustment for Gleason score, age, and PSA. Nonspecific HIF1<italic>α</italic> inhibitors appear to increase the progression‐free survival and reduce the risk of developing CRPC and metastases in patients on continuous ADT.</p> </abstract>