A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients

Invest New Drugs. 2007 Apr;25(2):139-46. doi: 10.1007/s10637-006-9019-2. Epub 2006 Nov 1.


Silibinin is a polyphenolic flavonoid isolated from milk thistle with anti-neoplastic activity in several in vitro and in vivo models of cancer, including prostate cancer. Silybin-phytosome is a commercially available formulation containing silibinin. This trial was designed to assess the toxicity of high-dose silybin-phytosome and recommend a phase II dose. Silybin-phytosome was administered orally to prostate cancer patients, giving 2.5-20 g daily, in three divided doses. Each course was 4 weeks in duration. Thirteen patients received a total of 91 courses of silybin-phytosome. Baseline patient characteristics included: median age of 70 years, median baseline prostate specific antigen (PSA) of 4.3 ng/ml, and a median ECOG performance status of 0. The most prominent adverse event was hyperbilirubinemia, with grade 1-2 bilirubin elevations in 9 of the 13 patients. The only grade 3 toxicity observed was elevation of alanine aminotransferase (ALT) in one patient; no grade 4 toxicity was noted. No objective PSA responses were observed. We conclude that 13 g of oral silybin-phytosome daily, in 3 divided doses, appears to be well tolerated in patients with advanced prostate cancer and is the recommended phase II dose. Asymptomatic liver toxicity is the most commonly seen adverse event.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Chemistry, Pharmaceutical
  • Dose-Response Relationship, Drug
  • Excipients
  • Follow-Up Studies
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / epidemiology
  • Glucuronides / blood
  • Glucuronides / metabolism
  • Glucuronides / urine
  • Humans
  • Liver Function Tests
  • Male
  • Phosphatidylcholines
  • Prostatic Neoplasms / drug therapy*
  • Silybin
  • Silymarin / adverse effects
  • Silymarin / analogs & derivatives*
  • Silymarin / pharmacokinetics
  • Silymarin / therapeutic use
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet


  • Antineoplastic Agents, Phytogenic
  • Excipients
  • Glucuronides
  • Phosphatidylcholines
  • Silymarin
  • silybin-phytosome
  • Silybin