TY - JOUR
T1 - Phase Ib placebo-controlled, tissue biomarker trial of diindolylmethane (BR-DIMNG) in patients with prostate cancer who are undergoing prostatectomy
AU - Gee, Jason R.
AU - Saltzstein, Daniel R.
AU - Messing, Edward
AU - Kim, Kyung Mann
AU - Kolesar, Jill
AU - Huang, Wei
AU - Havighurst, Thomas C.
AU - Harris, Linda
AU - Wollmer, Barbara W.
AU - Jarrard, David
AU - House, Margaret
AU - Parnes, Howard
AU - Bailey, Howard H.
N1 - Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - 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 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 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.
AB - 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 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 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.
KW - Chemoprevention
KW - Diindolymethane
KW - Prostate cancer
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U2 - 10.1097/CEJ.0000000000000189
DO - 10.1097/CEJ.0000000000000189
M3 - Article
C2 - 26313229
AN - SCOPUS:84973523332
SN - 0959-8278
VL - 25
SP - 312
EP - 320
JO - European Journal of Cancer Prevention
JF - European Journal of Cancer Prevention
IS - 4
ER -