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

本提案的总体主题是研究彩曲菌提取物（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增加剂量的PSK单独或联合标准多西他赛化疗的安全性和免疫效应。这项b期临床研究将包括安全性、耐受性、多西他赛药代动力学、先天免疫生物标志物和循环肿瘤细胞的测量。虽然日本肿瘤治疗的标准PSK剂量为3000 mg/天，但由于从未研究过更高剂量的PSK，而且雄激素剥夺和多西紫杉醇都会影响免疫系统，因此确定PSK单独和联合多西紫杉醇在该患者群体中的最大耐受剂量是有必要的。本研究的第二个目的是评估PSK对多西他赛药代动力学的影响，以确定PSK辅助治疗是否会影响多西他赛的清除率。该提案的第三个目标是提供PSK单独和加用多西紫杉醇治疗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作为化疗辅助药物的安全性证据，这项转化期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联合标准治疗的严谨研究将是转移性去势抵抗性前列腺癌患者癌症综合治疗的重要一步。

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.