title: A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction.
  
  
  METHODS
  Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks.
  
  
  RESULTS
  Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug.
  
  
  CONCLUSIONS
  Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.
authors.affiliation: Columbia University, New York, NY, USA.
authors.forename: Abby B
authors.initials: AB
authors.lastname: Siegel
authors.forename: Rupa
authors.initials: R
authors.lastname: Narayan
authors.forename: Rosa
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Abhishek
authors.initials: A
authors.lastname: Goyal
authors.forename: Judith S
authors.initials: JS
authors.lastname: Jacobson
authors.forename: Kara
authors.initials: K
authors.lastname: Kelly
authors.forename: Elena
authors.initials: E
authors.lastname: Ladas
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lunghofer
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hansen
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gustafson
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Flaig
authors.forename: Wei Yann
authors.initials: WY
authors.lastname: Tsai
authors.forename: David P H
authors.initials: DP
authors.lastname: Wu
authors.forename: Valerie
authors.initials: V
authors.lastname: Lee
authors.forename: Heather
authors.initials: H
authors.lastname: Greenlee
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020944:Silybum marianum / Q000009:adverse effects; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000009:adverse effects; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D000975:Antioxidants; D010713:Phosphatidylcholines; D012838:Silymarin; C067772:IdB 1016; D000077385:Silybin
keywords: dietary supplement; hepatocellular carcinoma; herbal supplement; milk thistle; phase I clinical trial