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.
Combining standard docetaxel therapy with PSK, a pharmacetical grade natural product, has the potential to significantly enhance antitumor immunity in people with castration-resistant prostate cancer. Preliminary evidence of safety and immune-enhancing actions warrant the proposed translational clinical trial, in which safety, pharmacokinetics of docetaxel chemotherapy, and immune biomarkers will be assessed.
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