phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects

• Published in: Journal of cancer research and clinical oncology Vol. 135; no. 9; pp. 1215 - 1221
• Main Authors: Deng, Gary, Lin, Hong, Seidman, Andrew, Fornier, Monica, D'Andrea, Gabriella, Wesa, Kathleen, Yeung, Simon, Cunningham-Rundles, Susanna, Vickers, Andrew J, Cassileth, Barrie
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.09.2009; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Administration, Oral; Adult; Aged; Alternative medicine; Antineoplastic agents; Biological and medical sciences; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Cancer Research; Clinical trials; Cohort Studies; Cytokines - biosynthesis; Dietary supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Grifola - chemistry; Grifola frondosa; Gynecology. Andrology. Obstetrics; Hematology; Humans; Immunology; Internal Medicine; Mammary gland diseases; Maximum Tolerated Dose; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Mushrooms; Neoplasm Staging; Oncology; Original Paper; Pharmacology. Drug treatments; Polysaccharides - administration & dosage; Polysaccharides - adverse effects; Polysaccharides - pharmacology; Tumors; Dietary supplement; Complementary and alternative medicine; Immunology; Botanical; Mushroom; Optimal dose; Clinical trial; Herbal; Breast cancer; Maitake; Breast disease; Extract; Basidiomycota; Fungi; Phase II trial; Supplementation; Dose; Human; Patient; Malignant tumor; Mammary gland diseases; Alternative medicine; Plant origin; Phase I trial; Polysaccharide; Cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-009-0562-z

Background Cancer patients commonly use dietary supplements to “boost immune function”. A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown. Methods In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days -7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoints were safety and tolerability. Results No dose-limiting toxicity was encountered. Two patients withdrew prior to completion of the study due to grade I possibly related side effects: nausea and joint swelling in one patient; rash and pruritus in the second. There was a statistically significant association between Maitake and immunologic function (p < 0.0005). Increasing doses of Maitake increased some immunologic parameters and depressed others; the dose-response curves for many endpoints were non-monotonic with intermediate doses having either immune enhancing or immune suppressant effects compared with both high and low doses. Conclusions Oral administration of a polysaccharide extract from Maitake mushroom is associated with both immunologically stimulatory and inhibitory measurable effects in peripheral blood. Cancer patients should be made aware of the fact that botanical agents produce more complex effects than assumed, and may depress as well as enhance immune function.