Journal article
Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy
European journal of cancer prevention, Vol.25(4), pp.312-320
07/01/2016
DOI: 10.1097/CEJ.0000000000000189
PMID: 26313229
Abstract
Epidemiologic, preclinical, and early phase I studies of the cruciferous vegetable bioactive metabolite, 3,3-diindolylmethane (DIM), support its potential prostate cancer chemopreventive ability. We performed a multicenter, double-blind, placebo-controlled trial of DIM in patients diagnosed with prostate cancer and scheduled for radical prostatectomy. A total of 45 patients with organ-confined prostate cancer were randomized to 21-28 days of an absorption-enhanced formulation of DIM (BR-DIMNG) at doses of 100 or 200mg per os twice daily or to placebo twice daily. Prostate tissue levels of DIM were the primary endpoint, with selected secondary biomarker endpoints including blood levels of DIM, total prostate-specific antigen, testosterone, and the insulin-like growth factor-1:insulin-like growth factor binding protein-3 ratio and the urinary 2-hydroxyestrone/16-hydroxyestrone ratio, obtained at baseline, at day 15, and before surgery, as well as tissue expression of androgen receptor, prostate-specific antigen, Ki67, caspase 3 with cytochrome p450 mRNA expression and genotyping (polymorphisms). DIM was well tolerated with excellent study compliance and relatively rapid accrual of all 45 patients within 1 year. DIM levels were detected in only seven of 28 prostate tissue specimens. There was a statistically significant difference in the change in the urinary 2-hydroxyestrone/16-hydroxyestrone ratio from baseline until before surgery between the placebo and 400mg DIM groups, with otherwise statistically nonsignificant changes in plasma biomarker expression. The administration of BR-DIMNG to prostate cancer patients before prostatectomy yields detectable plasma levels but without consistent or significant tissue accumulation or biomarker modulation. This study demonstrates the feasibility of biologic evaluation of relatively nontoxic preventive agents in the preprostatectomy setting with the potential for rapid accrual.
Details
- Title: Subtitle
- Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy
- Creators
- Jason R. Gee - University of Wisconsin Carbone Cancer CenterDaniel R. Saltzstein - Urology San AntonioEdward Messing - University of Rochester Medical CenterKyungMann Kim - University of Wisconsin Carbone Cancer CenterJill Kolesar - University of Wisconsin Carbone Cancer CenterWei Huang - University of Wisconsin Carbone Cancer CenterThomas C. Havighurst - University of Wisconsin Carbone Cancer CenterLinda Harris - University of Wisconsin Carbone Cancer CenterBarbara W. Wollmer - University of Wisconsin Carbone Cancer CenterDavid Jarrard - University of Wisconsin Carbone Cancer CenterMargaret House - National Cancer InstituteHoward Parnes - National Cancer InstituteHoward H. Bailey - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- European journal of cancer prevention, Vol.25(4), pp.312-320
- Publisher
- Lippincott Williams & Wilkins
- DOI
- 10.1097/CEJ.0000000000000189
- PMID
- 26313229
- ISSN
- 0959-8278
- eISSN
- 1473-5709
- Number of pages
- 9
- Grant note
- P30CA014520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) N01 CN35153; P30 CA014520 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) UL1TR000427 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) UL1TR000427 / NCATS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Language
- English
- Date published
- 07/01/2016
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696540602771
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