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

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Summary

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.

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Acknowledgments

The authors wish to acknowledge the invaluable research support of Spencer Green and Cynthia Snedden. This work was supported in part by a grant from the National Center for Complementary and Alternative Medicine (NCCAM), P30 CA046934 supplement.

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Flaig, T.W., Gustafson, D.L., Su, LJ. et al. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs 25, 139–146 (2007). https://doi.org/10.1007/s10637-006-9019-2

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  • DOI: https://doi.org/10.1007/s10637-006-9019-2

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