title: Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy.
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-DIM) at doses of 100 or 200 mg 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 400 mg DIM groups, with otherwise statistically nonsignificant changes in plasma biomarker expression. The administration of BR-DIM 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.
authors: aUniversity of Wisconsin Carbone Cancer Center, Madison, Wisconsin bUrology San Antonio Research, San Antonio, Texas cUniversity of Rochester Medical Center, Rochester, New York dDivision of Cancer Prevention, National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA.
authors: Jason R
authors: JR
authors: Gee
authors: Daniel R
authors: DR
authors: Saltzstein
authors: Edward
authors: E
authors: Messing
authors: KyungMann
authors: K
authors: Kim
authors: Jill
authors: J
authors: Kolesar
authors: Wei
authors: W
authors: Huang
authors: Thomas C
authors: TC
authors: Havighurst
authors: Linda
authors: L
authors: Harris
authors: Barbara W
authors: BW
authors: Wollmer
authors: David
authors: D
authors: Jarrard
authors: Margaret
authors: M
authors: House
authors: Howard
authors: H
authors: Parnes
authors: Howard H
authors: HH
authors: Bailey
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; C016392:3,3'-diindolylmethane