Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12061
Title: The effects of nonspecific HIF1α inhibitors on development of castrate resistance and metastases in prostate cancer.
Authors: Ranasinghe, Weranja K B;Sengupta, Shomik;Williams, Scott;Chang, Mike;Shulkes, Arthur;Bolton, Damien M;Baldwin, Graham S;Patel, Oneel
Affiliation: Department of Urology, Austin Health/University of Melbourne, Heidelberg, Victoria, Australia; Department of Surgery, Austin Health/University of Melbourne, Heidelberg, Victoria, Australia; Royal Melbourne Hospital, Melbourne, Australia.
Issue Date: 27-Jan-2014
Citation: Cancer Medicine 2014; 3(2): 245-51
Abstract: Expression of hypoxia-inducible factor (HIF)1α 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 HIF1α 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 HIF1α 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 HIF1α inhibitors. Both groups had similar characteristics, apart from patients on HIF1α inhibitors being older (70 years vs. 63.9 years). The median CRPC-free survival was longer in men using HIF1α 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 HIF1α 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 HIF1α inhibitors appear to increase the progression-free survival and reduce the risk of developing CRPC and metastases in patients on continuous ADT.
Internal ID Number: 24464861
URI: http://ahro.austin.org.au/austinjspui/handle/1/12061
DOI: 10.1002/cam4.189
URL: http://www.ncbi.nlm.nih.gov/pubmed/24464861
Type: Journal Article
Subjects: Castrate resistance
Hypoxia-inducible factor
inhibitors
metastases
prostate cancer
Aged
Aged, 80 and over
Disease-Free Survival
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit.antagonists & inhibitors.metabolism
Male
Middle Aged
Neoplasm Metastasis
Prostatic Neoplasms, Castration-Resistant.drug therapy.metabolism.pathology
Retrospective Studies
Survival Analysis
Appears in Collections:Journal articles

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