This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beer, T. M. Articles by Henner, W. D. Search for Related Content PubMed PubMed Citation Articles by Beer, T. M. Articles by Henner, W. D.

Randomized Study of High-Dose Pulse Calcitriol or Placebo prior to Radical Prostatectomy

¹ Division of Hematology and Medical Oncology, ² Department of Pathology, and ³ Division of Urology, Oregon Health & Science University and Portland VA Medical Center, Portland, Oregon

Requests for reprints: Tomasz M. Beer, Division of Hematology and Medical Oncology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, CR-145, Portland, OR 97239. Phone: 503-494-0365; Fax: 503-494-6197. E-mail: beert{at}ohsu.edu

Background: Cancer chemoprevention trials require enormous resources due to the large numbers of patients and the years of follow-up needed to achieve sufficient statistical power. Examination of candidate prevention agents using biomarkers as surrogate end points has been proposed as a method to rapidly identify promising agents for prevention trials. Treatment of patients with candidate agents prior to scheduled biopsy or surgical resection of malignancy allows for direct examination of the treatment effects on tumor tissue. In this study, we selected this approach to test several hypotheses about the effect of calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, on early-stage human prostate cancer.

Methods: After selection of surgical treatment for histologically confirmed adenocarcinoma of the prostate, patients were randomized to either calcitriol 0.5 µg/kg or placebo weekly for 4 weeks. The expression levels of the vitamin D receptor (VDR), proliferating cell nuclear antigen, PTEN (MMAC1/TEP1), c-Myc, transforming growth factor (TGF) ß receptor type II (TGFß RII), and Bcl-2 were quantified using immunohistochemistry in the patients' prostate specimens post surgery.

Results: Thirty-seven of 39 prostate tumors were evaluable for molecular end points. VDR expression was reduced in patients treated with calcitriol (mean, 75.3% of cells) compared with those that received placebo (mean, 98.6%; P = 0.005). Calcitriol treatment did not result in a statistically significant change in the fraction of cells expressing TGFß RII, PTEN, or proliferating cell nuclear antigen. Bcl-2 and c-Myc expression was at the lower limits of detection in both the calcitriol group and the placebo group; therefore, we were unable to determine whether drug treatment induced a significant change in these biomarkers.

Conclusions: High-dose calcitriol down-regulates VDR expression in human prostate cancer. Further study is needed to determine the biological consequences of VDR down-regulation in prostate cancer. This study shows that the use of the preprostatectomy model is feasible and can be used to test the effect of candidate chemopreventive agents on prostate cancer.

Key Words: Prostate cancer • clinical trial • phase II • calcitriol • vitamin D • 1,25-dihydroxyvitamin D • 1,25-dihydroxycholecalciferol

This article has been cited by other articles:

				A. Myrthue, B. L.S. Rademacher, J. Pittsenbarger, B. Kutyba-Brooks, M. Gantner, D. Z. Qian, and T. M. Beer The Iroquois Homeobox Gene 5 Is Regulated by 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer and Regulates Apoptosis and the Cell Cycle in LNCaP Prostate Cancer Cells Clin. Cancer Res., June 1, 2008; 14(11): 3562 - 3570. [Abstract] [Full Text] [PDF]

				G. E. Mullin and A. Dobs Vitamin D and Its Role in Cancer and Immunity: A Prescription for Sunlight Nutr Clin Pract, June 1, 2007; 22(3): 305 - 322. [Abstract] [Full Text] [PDF]

				W. Banach-Petrosky, X. Ouyang, H. Gao, K. Nader, Y. Ji, N. Suh, R. S. DiPaola, and C. Abate-Shen Vitamin d inhibits the formation of prostatic intraepithelial neoplasia in nkx3.1; pten mutant mice. Clin. Cancer Res., October 1, 2006; 12(19): 5895 - 5901. [Abstract] [Full Text] [PDF]

				S. Masuda and G. Jones Promise of vitamin D analogues in the treatment of hyperproliferative conditions. Mol. Cancer Ther., April 1, 2006; 5(4): 797 - 808. [Abstract] [Full Text] [PDF]