Enhancing innate immunity by combining PSK with docetaxel in/C.Higano/C.Wenner

通过 PSK 与多西他赛联合增强先天免疫 /C.Higano/C.Wenner

• 批准号: 8093336
• 负责人: LEANNA J STANDISH
• 金额: $ 55.65万
• 依托单位: BASTYR UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8093336
• 关键词: Address; Agaricales; Agonist; Androgens; Arts; Biological Factors; Biological Markers; Blood; Caring; Castration; Clinical Trials; Complementary and alternative medicine; Data; Dose; Drug Kinetics; Immune; Immune response; Immune system; Immunity; Immunologics; Japan; Malignant neoplasm of prostate; Maximum Tolerated Dose; Measures; Natural Immunity; Natural Killer Cells; Patients; Phase; Placebos; Polysaccharide-K; Resistance; Safety; TLR2 gene; Toll-like receptors; Tumor Markers; cancer therapy; chemotherapy; deprivation; docetaxel; neoplastic cell; novel; oncology; patient population; response; response marker; tool; translational clinical trial; tumor

The overall theme of this proposal is to study the effect of the Trametes versicolor mushroom extract, PSK, with standard Western oncologic treatments. In Project 2, the safety and immune effects of escalating doses of PSK alone and in combination with standard docetaxel chemotherapy will be studied in patients with metastatic castration-resistant prostate cancer. The Phase 1 b study will include measures of safety, tolerability, docetaxel pharmacokinetics, innate immunity biomarkers, and circulating tumor cells. Although a standard PSK dose of 3000 mg/day has been established for oncology therapy in Japan, the first aim to determine a maximum tolerated dose of PSK alone and combined with docetaxel in this patient population is warranted because higher doses of PSK have never been studied and because both androgen deprivation and docetaxel impact the immune system. The second aim of this study to assess the effects of PSK on docetaxel pharmacokinetics will determine whether adjunctive treatment with PSK influences the clearance of docetaxel. The third aim of this proposal will provide key translational data on the effects of PSK alone and added to docetaxel therapy on biomarkers of innate antitumor immunity and circulating tumor cells. Given the evidence of safety of PSK when used as an adjunctive agent to chemotherapy, this translational phase lb clinical trial is warranted. Determining the effects of addition of PSK to standard chemotherapy will offer a better understanding of PSK's mechanisms of action in the context of prostate cancer. Rigorous study of PSK in combination with standard therapy will be an important step forward in integrative cancer therapy for patients with metastatic castration-resistant prostate cancer.

该提案的总体主题是研究栓菌蘑菇提取物 PSK 与标准西方肿瘤治疗的效果。在项目 2 中，将在转移性去势抵抗性前列腺癌患者中研究单独增加 PSK 剂量以及与标准多西他赛化疗联合使用的安全性和免疫效果。 1 b 期研究将包括安全性、耐受性、多西紫杉醇药代动力学、先天免疫生物标志物和循环肿瘤细胞的测量。尽管日本已为肿瘤治疗制定了 3000 毫克/天的标准 PSK 剂量，但首要目标是确定该患者群体中单独使用 PSK 以及联合多西他赛的最大耐受剂量，因为从未研究过更高剂量的 PSK而且因为雄激素剥夺和多西紫杉醇都会影响免疫系统。本研究的第二个目的是评估 PSK 对多西紫杉醇药代动力学的影响，以确定 PSK 辅助治疗是否会影响多西紫杉醇的清除率。该提案的第三个目标是提供关于单独使用 PSK 以及添加到多西紫杉醇治疗中对先天抗肿瘤免疫和循环肿瘤细胞生物标志物的影响的关键转化数据。鉴于 PSK 作为化疗辅助药物使用时的安全性证据，这项 lb 期转化临床试验是有必要的。确定在标准化疗中添加 PSK 的效果将有助于更好地了解 PSK 在前列腺癌中的作用机制。 PSK 与标准治疗相结合的严格研究将是转移性去势抵抗性前列腺癌患者综合癌症治疗的重要一步。