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

该提案的总体主题是研究变色栓菌蘑菇提取物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递增剂量的PSK单独使用和与标准多西他赛化疗联合使用的安全性和免疫效应。I期B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。尽管在日本已经确定了3000 mg/天的PSK标准剂量用于肿瘤治疗，但确定该患者人群中PSK单药和与多西他赛联合给药的最大耐受剂量的第一个目标是必要的，因为从未研究过更高剂量的PSK，并且因为雄激素剥夺和多西他赛都会影响免疫系统。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的连续治疗是否影响多西他赛的清除。该提案的第三个目的将提供关于PSK单独和添加到多西他赛治疗中对先天性抗肿瘤免疫和循环肿瘤细胞的生物标志物的影响的关键翻译数据。考虑到PSK用作化疗抑制剂时的安全性证据，该转化Ib期临床试验是必要的。确定PSK添加到标准化疗的效果将提供更好地了解PSK在前列腺癌背景下的作用机制。对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。

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.