期刊
PROSTATE
卷 73, 期 9, 页码 970-978出版社
WILEY-BLACKWELL
DOI: 10.1002/pros.22644
关键词
prostate cancer; vitamin D; chemoprevention
资金
- N01 National Institutes of Health [CN95130, P30 CA14520]
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.
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