title: A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects.
abstract: 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.
authors.affiliation: Integrative Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. dengg@mskcc.org
authors.forename: Gary
authors.initials: G
authors.lastname: Deng
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.forename: Andrew
authors.initials: A
authors.lastname: Seidman
authors.forename: Monica
authors.initials: M
authors.lastname: Fornier
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wesa
authors.forename: Simon
authors.initials: S
authors.lastname: Yeung
authors.forename: Susanna
authors.initials: S
authors.lastname: Cunningham-Rundles
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Vickers
authors.forename: Barrie
authors.initials: B
authors.lastname: Cassileth
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D048691:Grifola / Q000737:chemistry*; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011134:Polysaccharides / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D011134:Polysaccharides