title: A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer.
abstract: BACKGROUND
  Silibinin is a polyphenolic flavonolignan derived from milk thistle (Silybum marianium) with anti-oxidant properties. The purpose of the current trial was to determine the tissue and blood effects of high-dose silybin-phytosome in prostate cancer patients.
  
  
  METHODS
  Subjects with localized prostate cancer planning for a prostatectomy were eligible to enroll. Six patients received 13 g of silybin-phytosome daily with six additional participants serving as control subjects.
  
  
  RESULTS
  Patients in the treatment arm received silybin-phytosome for 14-31 days (mean was 20 days) prior to surgery. Silibinin blood levels were measured 1 hr after the first silybin-phytosome dose with a mean value of 19.7 microM. Trough silibinin levels were assessed at the end of the trial with an average concentration of 1.2 microM. In contrast to the high peak levels of silibinin observed in blood, the highest silibinin level observed in the harvested prostate tissue was 496.6 pmol/g. There were no significant differences noted in baseline and post-treatment blood levels of IGF-I and IGFBP-3. One of the treated patients developed a grade 4 post-operative thromboembolic event. The other observed toxicities in the treatment group were mild: four subjects had diarrhea and one had asymptomatic grade 2 hyperbilirubinemia which was transient.
  
  
  CONCLUSIONS
  High-dose oral silybin-phytosome achieves high blood concentrations transiently, but low levels of silibinin are seen in prostate tissue. Silibinin's lack of tissue penetration may be explained by its short half-life, the brief duration of therapy in this study or an active process removing silibinin from the prostate.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA. thomas.flaig@ucdenver.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Flaig
authors.forename: Michael
authors.initials: M
authors.lastname: Glodé
authors.forename: Daniel
authors.initials: D
authors.lastname: Gustafson
authors.forename: Adrie
authors.initials: A
authors.lastname: van Bokhoven
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Tao
authors.forename: Shandra
authors.initials: S
authors.lastname: Wilson
authors.forename: Lih-Jen
authors.initials: LJ
authors.lastname: Su
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Gail
authors.initials: G
authors.lastname: Harrison
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwal
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use; D000975:Antioxidants / Q000493:pharmacokinetics / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D000077385:Silybin; D012838:Silymarin / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D018972:Insulin-Like Growth Factor Binding Protein 3; D012838:Silymarin; D000077385:Silybin; D007334:Insulin-Like Growth Factor I