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The effects of nonspecific HIF 1 α inhibitors on development of castrate resistance and metastases in prostate cancer
Author(s) -
Ranasinghe Weranja K. B.,
Sengupta Shomik,
Williams Scott,
Chang Mike,
Shulkes Arthur,
Bolton Damien M.,
Baldwin Graham,
Patel Oneel
Publication year - 2014
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.189
Subject(s) - medicine , prostate cancer , androgen deprivation therapy , metastasis , oncology , androgen receptor , cancer , prostate specific antigen , urology
Expression of hypoxia‐inducible factor ( HIF )1 α 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 HIF 1 α 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 HIF 1 α 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 HIF 1 α inhibitors. Both groups had similar characteristics, apart from patients on HIF 1 α inhibitors being older (70 years vs. 63.9 years). The median CRPC ‐free survival was longer in men using HIF 1 α inhibitors compared to those not on inhibitors (6.7 years vs. 2.7 years, P  = 0.01) and there was a 71% reduction in the risk of developing CRPC ( HR 0.29 [95% CI 0.10–0.78] P  = 0.02) after adjustment for Gleason score, age, and prostate‐specific antigen ( PSA ). The median metastasis‐free survival in men on HIF 1 α inhibitors was also significantly longer compared to those on no inhibitors (5.1 years vs. 2.6 years, P  = 0.01) with an 81% reduction in the risk of developing metastases ( HR 0.19 [ CI 0.05–0.76] P  = 0.02) after adjustment for Gleason score, age, and PSA . Nonspecific HIF 1 α inhibitors appear to increase the progression‐free survival and reduce the risk of developing CRPC and metastases in patients on continuous ADT .

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