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

这项建议的总体主题是研究曲美特斯杂色蘑菇提取物PSK与标准西方肿瘤学治疗的效果。在项目2中，将对转移性去势抵抗前列腺癌患者单独和联合标准多西紫杉醇化疗的剂量递增的PSK的安全性和免疫效果进行研究。第一阶段b研究将包括安全措施， 耐受性、多西紫杉醇药代动力学、天然免疫生物标记物和循环肿瘤细胞。虽然日本已经建立了每天3000毫克的标准PSK剂量用于肿瘤治疗，但第一个目标是确定PSK在这些患者群体中单独使用和与多西紫杉醇联合使用的最大耐受量是合理的，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。这项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，这将决定PSK辅助治疗是否影响多西紫杉醇的清除。这项建议的第三个目标将提供关于PSK单独以及与多西紫杉醇联合治疗对先天抗肿瘤免疫和循环肿瘤细胞生物标记物的影响的关键翻译数据。有证据表明PSK作为化疗的辅助药物是安全的，这项转化性的Lb期临床试验是有必要的。确定在标准化疗中加入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结合标准疗法的严格研究将是抗去势转移性前列腺癌患者综合癌症治疗的重要一步。

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.