A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients
A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients
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DOI：
10.1007/s10637-006-9019-2
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发表时间：
2007-04-01
影响因子：
3.4
通讯作者：
Glode, L. Michael
中科院分区：
文献类型：
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作者：
Flaig, Thomas W.;Gustafson, Daniel L.;Glode, L. Michael
水飞蓟宾是一种从水飞蓟中分离出来的多酚类黄酮，对包括前列腺癌在内的多种肿瘤模型具有抗肿瘤活性。水飞蓟宾-植物体是一种商用配方含有水飞蓟宾。该试验旨在评估高剂量水飞蓟宾-植物体的毒性，并推荐II期剂量。水飞蓟宾-植物原体被口服给前列腺癌患者，每天2.5-20克，分三次给药。每个疗程为4周。13例患者共接受了91个疗程的水飞蓟宾-磷脂复合物治疗。基线患者特征包括：中位年龄70岁，中位基线前列腺特异性抗原（PSA）为4.3 ng/ml，中位ECOG表现状态为0。最突出的不良事件是高胆红素血症，13例患者中有9例出现1-2级胆红素升高。唯一观察到的3级毒性是一名患者丙氨酸转氨酶（ALT）升高；未发现4级毒性。没有观察到客观的PSA反应。我们的结论是，晚期前列腺癌患者每天口服13克水飞蓟宾-植物体，分3次给药，似乎耐受性良好，是推荐的II期剂量。无症状肝毒性是最常见的不良事件。
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.