title: Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium.
abstract: OBJECTIVE
  High-grade prostatic intraepithelial neoplasia (HGPIN) is a putative precursor of invasive prostate cancer (PCa). Preclinical evidence suggests vitamin E, selenium, and soy protein may prevent progression of HGPIN to PCa. This hypothesis was tested in a randomized phase III double-blind study of daily soy (40 g), vitamin E (800 U), and selenium (200 μg) versus placebo.
  
  
  METHODS
  Three hundred three men in 12 Canadian centers were analyzed. The main eligibility criterion was confirmed HGPIN in at least one of two biopsies within 18 months of random assignment. Treatment was administered daily for 3 years. Follow-up prostate biopsies occurred at 6, 12, 24, and 36 months postrandomization. The primary end point was time to development of invasive PCa. Kaplan-Meier plots and log-rank tests were used to compare two treatment groups for this end point.
  
  
  RESULTS
  For all patients, the median age was 62.8 years. The median baseline prostate-specific antigen (PSA; n = 302) was 5.41 ug/L; total testosterone (n = 291) was 13.4 nmol/L. Invasive PCa developed among 26.4% of patients. The hazard ratio for the nutritional supplement to prevent PCa was 1.03 (95% CI, 0.67 to 1.60; P = .88). Gleason score distribution was similar in both groups with 83.5% of cancers graded Gleason sum of 6. Baseline age, weight, PSA, and testosterone did not predict for development of PCa. The supplement was well tolerated with flatulence reported more frequently (27% v 17%) among men receiving micronutrients.
  
  
  CONCLUSIONS
  This trial does not support the hypothesis that combination vitamin E, selenium, and soy prevents progression from HGPIN to PCa.
authors.affiliation: University Health Network, Princess Margaret Hospital, 610 University Ave., Toronto, Ontario Canada. Neil.Fleshner@uhn.on.ca
authors.forename: Neil E
authors.initials: NE
authors.lastname: Fleshner
authors.forename: Linda
authors.initials: L
authors.lastname: Kapusta
authors.forename: Bryan
authors.initials: B
authors.lastname: Donnelly
authors.forename: Simon
authors.initials: S
authors.lastname: Tanguay
authors.forename: Joseph
authors.initials: J
authors.lastname: Chin
authors.forename: Karen
authors.initials: K
authors.lastname: Hersey
authors.forename: Anne
authors.initials: A
authors.lastname: Farley
authors.forename: Ken
authors.initials: K
authors.lastname: Jansz
authors.forename: D Robert
authors.initials: DR
authors.lastname: Siemens
authors.forename: Kiril
authors.initials: K
authors.lastname: Trpkov
authors.forename: Louis
authors.initials: L
authors.lastname: Lacombe
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Parulekar
mesh_terms: D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D017430:Prostate-Specific Antigen / Q000097:blood; D019048:Prostatic Intraepithelial Neoplasia / Q000150:complications*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D012643:Selenium / Q000008:administration & dosage* / Q000009:adverse effects; D030262:Soybean Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D013739:Testosterone / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D030262:Soybean Proteins; D014810:Vitamin E; D013739:Testosterone; D017430:Prostate-Specific Antigen; D012643:Selenium