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.
|Coy, Catherine; Standish, Leanna J; Bender, Geoff et al. (2015) Significant Correlation between TLR2 Agonist Activity and TNF-Î± Induction in J774.A1 Macrophage Cells by Different Medicinal Mushroom Products. Int J Med Mushrooms 17:713-22|
|Quayle, Kenneth; Coy, Catherine; Standish, Leanna et al. (2015) The TLR2 agonist in polysaccharide-K is a structurally distinct lipid which acts synergistically with the protein-bound Î²-glucan. J Nat Med 69:198-208|
|Engel, Abbi L; Sun, Guan-Cheng; Gad, Ekram et al. (2013) Protein-bound polysaccharide activates dendritic cells and enhances OVA-specific T cell response as vaccine adjuvant. Immunobiology 218:1468-76|
|Standish, Leanna J; Sweet, Erin; Naydis, Eleonora et al. (2013) Can we demonstrate that breast cancer "integrative oncology" is effective? A methodology to evaluate the effectiveness of integrative oncology offered in community clinics. Integr Cancer Ther 12:126-35|
|Inatsuka, Carol; Yang, Yi; Gad, Ekram et al. (2013) Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK. Cancer Immunol Immunother 62:1335-45|
|Wenner, Cynthia A; Martzen, Mark R; Lu, Hailing et al. (2012) Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer. Int J Oncol 40:905-13|
|Lu, Hailing; Yang, Yi; Gad, Ekram et al. (2011) TLR2 agonist PSK activates human NK cells and enhances the antitumor effect of HER2-targeted monoclonal antibody therapy. Clin Cancer Res 17:6742-53|
|Lu, Hailing; Yang, Yi; Gad, Ekram et al. (2011) Polysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clin Cancer Res 17:67-76|