A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer.
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.
Flaig
Thomas W
TW
Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA. thomas.flaig@ucdenver.edu
Glodé
Michael
M
Gustafson
Daniel
D
van Bokhoven
Adrie
A
Tao
Yuzhen
Y
Wilson
Shandra
S
Su
Lih-Jen
LJ
Li
Yuan
Y
Harrison
Gail
G
Agarwal
Rajesh
R
Crawford
E David
ED
Lucia
M Scott
MS
Pollak
Michael
M
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
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D018972:Insulin-Like Growth Factor Binding Protein 3; D012838:Silymarin; D000077385:Silybin; D007334:Insulin-Like Growth Factor I