Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy

Tomasz (Tom) Beer, Anne Myrthue, Mark Garzotto, Michael F. O'Hara, Raymond Chin, Bruce A. Lowe, Michelle A. Montalto, Christopher Corless, W. David Henner

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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 μ/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) β receptor type II (TGFβ 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 TGFβ 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.

Original languageEnglish (US)
Pages (from-to)2225-2232
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume13
Issue number12
StatePublished - Dec 2004

Fingerprint

Calcitriol
Prostatectomy
Placebos
Calcitriol Receptors
Prostatic Neoplasms
Prostate
Biomarkers
Proliferating Cell Nuclear Antigen
Transforming Growth Factors
Neoplasms
Down-Regulation
Therapeutics
Growth Factor Receptors
Chemoprevention
Vitamin D
Limit of Detection
Adenocarcinoma
Immunohistochemistry
Biopsy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy. / Beer, Tomasz (Tom); Myrthue, Anne; Garzotto, Mark; O'Hara, Michael F.; Chin, Raymond; Lowe, Bruce A.; Montalto, Michelle A.; Corless, Christopher; Henner, W. David.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 13, No. 12, 12.2004, p. 2225-2232.

Research output: Contribution to journalArticle

Beer, TT, Myrthue, A, Garzotto, M, O'Hara, MF, Chin, R, Lowe, BA, Montalto, MA, Corless, C & Henner, WD 2004, 'Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy', Cancer Epidemiology Biomarkers and Prevention, vol. 13, no. 12, pp. 2225-2232.
Beer, Tomasz (Tom) ; Myrthue, Anne ; Garzotto, Mark ; O'Hara, Michael F. ; Chin, Raymond ; Lowe, Bruce A. ; Montalto, Michelle A. ; Corless, Christopher ; Henner, W. David. / Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy. In: Cancer Epidemiology Biomarkers and Prevention. 2004 ; Vol. 13, No. 12. pp. 2225-2232.
@article{7cdcb49cae914482a63e240928a75155,
title = "Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy",
abstract = "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 μ/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) β receptor type II (TGFβ 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 TGFβ 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.",
author = "Beer, {Tomasz (Tom)} and Anne Myrthue and Mark Garzotto and O'Hara, {Michael F.} and Raymond Chin and Lowe, {Bruce A.} and Montalto, {Michelle A.} and Christopher Corless and Henner, {W. David}",
year = "2004",
month = "12",
language = "English (US)",
volume = "13",
pages = "2225--2232",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy

AU - Beer, Tomasz (Tom)

AU - Myrthue, Anne

AU - Garzotto, Mark

AU - O'Hara, Michael F.

AU - Chin, Raymond

AU - Lowe, Bruce A.

AU - Montalto, Michelle A.

AU - Corless, Christopher

AU - Henner, W. David

PY - 2004/12

Y1 - 2004/12

N2 - 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 μ/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) β receptor type II (TGFβ 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 TGFβ 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.

AB - 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 μ/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) β receptor type II (TGFβ 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 TGFβ 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.

UR - http://www.scopus.com/inward/record.url?scp=11144245281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144245281&partnerID=8YFLogxK

M3 - Article

C2 - 15598784

AN - SCOPUS:11144245281

VL - 13

SP - 2225

EP - 2232

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 12

ER -