Journal article
Phase II open label, multi-center clinical trial of modulation of intermediate endpoint biomarkers by 1-hydroxyvitamin D2 in patients with clinically localized prostate cancer and high grade pin
The Prostate, Vol.73(9), pp.970-978
06/01/2013
DOI: 10.1002/pros.22644
PMCID: PMC3755376
PMID: 23335089
Abstract
BACKGROUND Prostate cancer is the most common malignancy and second leading cause of cancer related deaths in American men supporting the study of prostate cancer chemoprevention. Major risk factors for this disease have been associated with low serum levels of vitamin D. Here, we evaluate the biologic activity of a less calcemic vitamin D analog 1-hydroxyvitamin D2 [1-OH-D2] (Bone Care International, Inc.) in patients with prostate cancer and high grade prostatic intraepithelial neoplasia (HG PIN). METHODS Patients with clinically organ-confined prostate cancer and HG PIN were randomized to 1-OH-D2 versus placebo for 28 days prior to radical prostatectomy. Intermediate endpoint biomarkers included serum vitamin D metabolites, TGF ss 1/2, free/total PSA, IGF-1, IGFBP-3, bFGF, and VEGF. Tissue endpoints included histology, MIB-1 and TUNEL staining, microvessel density and factor VIII staining, androgen receptor and PSA, vitamin D receptor expression and nuclear morphometry. RESULTS The 1-OH-D2 vitamin D analog was well tolerated and could be safely administered with good compliance and no evidence of hypercalcemia over 28 days. While serum vitamin D metabolite levels only slightly increased, evidence of biologic activity was observed with significant reductions in serum PTH levels. TGF-ss 2 was the only biomarker significantly altered by vitamin D supplementation. Whether reduced TGF-ss 2 levels in our study is an early indicator of response to vitamin D remains unclear. CONCLUSIONS While further investigation of vitamin D may be warranted based on preclinical studies, results of the present trial do not appear to justify evaluation of 1-OH-D2 in larger clinical prostate cancer prevention studies. Prostate 73: 970978, 2013. (c) 2013 Wiley Periodicals, Inc.
Details
- Title: Subtitle
- Phase II open label, multi-center clinical trial of modulation of intermediate endpoint biomarkers by 1-hydroxyvitamin D2 in patients with clinically localized prostate cancer and high grade pin
- Creators
- Jason Gee - University of Wisconsin Carbone Cancer CenterHoward Bailey - Univ Wisconsin, Carbone Canc Ctr, Madison, WI USAKyungMann Kim - Univ Wisconsin, Carbone Canc Ctr, Madison, WI USAJill Kolesar - Univ Wisconsin, Carbone Canc Ctr, Madison, WI USATom Havighurst - Univ Wisconsin, Carbone Canc Ctr, Madison, WI USAKendra D. Tutsch - Univ Wisconsin, Carbone Canc Ctr, Madison, WI USAWilliam See - Med Coll Wisconsin, Milwaukee, WI 53226 USAMichael B. Cohen - University of IowaNick Street - University of IowaLeon LeVan - Bone Care Ctr, Middleton, WI USADavid Jarrard - Univ Wisconsin, Carbone Canc Ctr, Madison, WI USAGeorge Wilding - Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA
- Resource Type
- Journal article
- Publication Details
- The Prostate, Vol.73(9), pp.970-978
- DOI
- 10.1002/pros.22644
- PMID
- 23335089
- PMCID
- PMC3755376
- NLM abbreviation
- Prostate
- ISSN
- 0270-4137
- eISSN
- 1097-0045
- Publisher
- Wiley
- Number of pages
- 9
- Grant note
- N01CN095130 / DIVISION OF CANCER PREVENTION AND CONTROL; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CN95130; P30 CA14520 / N01 National Institutes of Health P30CA014520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 06/01/2013
- Academic Unit
- Pharmacy; Bus Admin College; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Nursing; Computer Science; Business Analytics
- Record Identifier
- 9984695801502771
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