A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer.

Abstract

Silybin-phosphatidylcholine is an orally bioavailable complex of silybin, a polyphenolic flavonolignan derived from milk thistle, endowed with potential anticancer activity in preclinical models. The purpose of this window of opportunity trial was to determine, for the first time in early breast cancer patients, the breast tissue distribution of silybin. Twelve breast cancer patients received silybin-phosphatidylcholine, 2.8 g daily for 4 weeks prior to surgery. Silybin levels were measured before (SIL) and after (TOT-SIL) enzymatic hydrolysis by high-performance liquid chromatography (HPLC)-MS/MS in biologic samples (plasma, urine, breast cancer, and surrounding normal tissue). Fasting blood samples were taken at baseline, before the last administration, and 2 hours later. All patients were fully compliant and completed the treatment program. No toxicity was observed. SIL and TOT-SIL were undetectable in baseline samples. Despite a high between-subject variability, repeated administration of Siliphos achieved levels of TOT-SIL of 31,121 to 7,654 ng/mL in the plasma and up to 1,375 ng/g in breast cancer tissue. SIL concentrations ranged from 10,861 to 1,818 ng/mL in plasma and up to 177 ng/g in breast cancer tissue. Median TOT-SIL concentration was higher in the tumor as compared with the adjacent normal tissue (P = 0.018). No significant change in either blood levels of IGF-I and nitric oxide or Ki-67 in tumors was noted. Silybin-phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue. These findings provide the basis for a future phase II biomarker trial in breast cancer prevention.

• Authors: Matteo Lazzeroni, Aliana Guerrieri-Gonzaga, Sara Gandini, Harriet Johansson, Davide Serrano, Massimiliano Cazzaniga, Valentina Aristarco, Antonella Puccio, Serena Mora, Pietro Caldarella, Gianmatteo Pagani, Giancarlo Pruneri, Antonella Riva, Giovanna Petrangolini, Paolo Morazzoni, Andrea DeCensi, Bernardo Bonanni
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 9 Issue 1 Pg. 89-95 (Jan 2016) ISSN: 1940-6215 [Electronic] United States
• PMID: 26526990 (Publication Type: Clinical Trial, Journal Article)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Phosphatidylcholines
• Silymarin
• Silybin

Topics

• Administration, Oral
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Biological Availability
• Biomarkers, Tumor
• Breast Neoplasms (drug therapy, immunology)
• Chromatography, High Pressure Liquid
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Hydrolysis
• Middle Aged
• Phosphatidylcholines (administration & dosage, pharmacokinetics)
• Reproducibility of Results
• Silybin
• Silymarin (administration & dosage, pharmacokinetics)
• Tandem Mass Spectrometry