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A study of high‐dose oral silybin‐phytosome followed by prostatectomy in patients with localized prostate cancer
Author(s) -
Flaig Thomas W.,
Glodé Michael,
Gustafson Daniel,
van Bokhoven Adrie,
Tao Yuzhen,
Wilson Shandra,
Su LihJen,
Li Yuan,
Harrison Gail,
Agarwal Rajesh,
Crawford E. David,
Lucia M. Scott,
Pollak Michael
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21118
Subject(s) - silibinin , medicine , prostate cancer , silybum marianum , prostatectomy , prostate , urology , gastroenterology , surgery , cancer , pharmacology , traditional medicine
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 µM. Trough silibinin levels were assessed at the end of the trial with an average concentration of 1.2 µM. 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. Prostate 70: 848–855, 2010. © 2010 Wiley‐Liss, Inc.