Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study.

BACKGROUND: Myelodysplastic syndromes (MDS) are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia. Maitake mushroom beta-glucan, a dietary supplement, stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury. This phase II trial examined the effects of Maitake on innate immune function in MDS. METHODS: Myelodysplastic syndromes patients with International Prognostic Scoring System Low- and Intermediate-1-risk disease received oral Maitake extract at 3 mg/kg twice daily for 12 weeks. Primary endpoints included neutrophil count and function tested as endogenous or stimulated neutrophil production of reactive oxygen species (ROS) by flow cytometry compared with age-matched healthy controls (HC). ROS activators were Escherichia coli, phorbol ester, and the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Complete blood counts, chemistry panels, iron studies, and monocyte function were evaluated. RESULTS: Of 21 patients enrolled, 18 completed the study and were evaluable. Maitake increased endogenous (basal) neutrophil (p = 0.005) and monocyte function (p = 0.021). Pre-treatment monocyte response to E. coli was reduced in MDS patients compared with HC (p = 0.002) and increased (p = 0.0004) after treatment. fMLP-stimulated ROS production response also increased (p = 0.03). Asymptomatic eosinophilia occurred in 4 patients (p = 0.014). Other changes in albumin, hemoglobin, and total protein were not clinically relevant. CONCLUSIONS: Maitake was well tolerated. Enhanced in vitro neutrophil and monocyte function following treatment demonstrate that Maitake has beneficial immunomodulatory potential in MDS. Further study is warranted.

Serum 25-hydroxy vitamin D and survival in advanced colorectal cancer: a retrospective analysis.

Higher serum 25-hydroxy vitamin D [25(OH)D] levels are associated with decreased colorectal cancer (CRC) incidence. In this retrospective study of Stage IV CRC patients, we evaluate whether 25(OH)D levels at diagnosis correlate with survival. Stored sera from carcinoembryonic antigen (CEA) measurements obtained between February 2005 and March 2006 were screened. The first 250 patients with CEA ± 30 days of Stage IV CRC diagnosis were included. Serum 25(OH)D levels were determined and categorized as adequate ≥ 30 ng/mL, or deficient <30 ng/mL. Multivariable Cox regression models controlling for albumin and Eastern Cooperative Oncology Group performance status were used to investigate whether higher 25(OH)D levels were associated with prolonged survival. A total of 207 patients (83%) were vitamin D-deficient (median = 21 ng/mL), with deficiencies significantly more likely among non-Hispanic black patients (P = 0.009). Higher levels were associated with prolonged survival in categorical variable analysis: adequate vs. deficient, hazard ratio = 0.61, 95% confidence interval = 0.38-0.98, P = 0.041. A majority of newly diagnosed Stage IV CRC patients are vitamin D-deficient. Our data suggest that higher 25(OH)D levels are associated with better overall survival. Clinical trials to determine whether aggressive vitamin D repletion would improve outcomes for vitamin D-deficient CRC patients are warranted.

Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity.

Bone marrow myelotoxicity is a major limitation of chemotherapy. While granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative approaches to support hematopoietic recovery are sought. We previously found that a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and spared HPC from doxorubicin toxicity in vitro. This investigation assessed the effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose of Ptx (90-120 mg/kg) given to B6D2F1mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 microg/kg) or Ptx alone were compared for effects on the dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and spleen, and granulocyte/monocyte production of reactive oxygen species (ROS). Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p = 0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days after Ptx. After two additional days (Ptx post-day 4), MBG restored granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The studies indicate that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury.

The Public Health Impact of Herbs and Nutritional Supplements.

Dietary supplement use has increased exponentially in recent years despite the lack of regulatory oversight and in the face of growing safety concerns. This paper provides an overview of the public health implications and safety concerns associated with dietary supplement use, especially by cancer patients. Botanical research is actively pursued at the Memorial Sloan-Kettering Cancer Center (MSKCC) Integrative Medicine department. Work of the MSKCC Center for the Study of Botanical Immunomodulators is described, and guidelines for cancer patients' use of dietary supplements outlined. Herbs and other botanicals are complex, physiologically active agents, but little is known about most of the popular, widely available dietary supplements. Herb-drug interactions, a major concern, are exacerbated in the cancer setting. Biologically active agents may interfere with chemotherapy and other prescription medications. They may exert anti-coagulant activity at rather inconvenient times such as during surgery, and create other serious problems. Research on the bioavailability, effective dosage, safety and benefits of these complex agents is sorely needed. Oncology professionals and other healthcare providers should educate themselves and their patients about these issues. Probably the largest, continuously-updated free information resource is MSKCC's AboutHerbs website (www.mskcc.org/AboutHerbs).

Integrative oncology: complementary therapies for cancer survivors.

Cancer survivors experience a wide range of symptoms during and following completion of treatment, and some of these symptoms may persist for years or even decades. While pharmacologic treatments relieve many symptoms, they too may produce difficult side effects. Complementary therapies are noninvasive, inexpensive, and useful in controlling symptoms and improving quality of life, and they may be accessed by patients themselves. Rigorous scientific research has produced evidence that acupuncture, massage therapy, music, and mind-body therapies effectively and safely reduce physical and emotional symptoms. These therapies provide a favorable risk-benefit ratio and permit cancer survivors to help manage their own care.

Recommendations and guidelines regarding the preferred research protocol for investigating the impact of an optimal healing environment on patients with substance abuse.

The addictive disorders affect every aspect of a person's life, and thus the most effective interventions are those that address many or all of these issues. Although the initial evaluation and intake process for addiction assessment is lengthy, this process does give the practitioner an opportunity to provide what can be considered an optimal healing environment (OHE) in treating the addictive disorders. In addition to our traditional medical treatment modalities of pharmacotherapy and psychotherapy, many complementary and alternative treatment modalities address and provide additional support for the holistic approach to treatment and recovery. The important role of spirituality in obtaining and maintaining recovery and sobriety has been recognized for many years. Because one specific treatment is not effective for all people and for all of the addictive disorders, using a holistic approach and individualizing the treatment regimen is the recommended approach to disease intervention and establishing an OHE. There are instruments available for measuring the facility, the staff, and the patient in their contributions to providing an OHE for substance abuse treatment. This paper suggests study design considerations for investigating the impact of an OHE on the results of treatment and specific instruments designed for use in patients with addictive disorders.

Recommendations and guidelines regarding the preferred research protocol for investigating the impact of an optimal healing environment on patients with hypertension.

Cardiovascular disease is the leading cause of death in the United States. Hypertension is the most common single reason for visits to primary care physicians accounting for more than 35 million visits annually. Pharmacotherapy can achieve adequate control of blood pressure. Multiple interventions compares to single therapies are more efficacious in treating hypertension, and this fact supports using the holistic approach to hypertension treatment. Implementing an optimal healing environment (OHE) in a hypertension treatment regimen has the potential to impact not only health care costs, but also to optimize blood pressure control, and thus decrease the total cardiovascular disease burden. The research questions for the study of OHE in hypertension may differ between the individual patient perspective and the public health perspective. The use of a 2 x 2 factorial design would allow analysis of both perspectives simultaneously. Using an OHE setting with multiple interventions in formulating an individualized approach to hypertension management merits further exploration and research.

Is there a role for complementary therapy in the management of leukemia?

Patients with leukemia often seek additional treatments not prescribed by their oncologist in an effort to improve their cancer treatment outcome or to manage symptoms. Complementary therapies are used in conjunction with traditional cancer treatments to decrease symptoms and side effects associated with cancer or cancer treatment, and to improve patients' overall quality of life. Complementary therapies are distinct from so-called 'alternative' therapies, which are unproven, ineffective and may postpone or interfere with mainstream cancer treatment. Complementary therapies are pleasant, inexpensive, nonpharmacologic and effective. For patients with leukemia, the complementary therapies that are always appropriate include mind-body interventions, such as self-hypnosis, meditation, guided imagery and breath awareness. Massage and reflexology (foot massage) decrease symptoms with effects lasting at least 2 days following treatment. Acupuncture is very beneficial for symptom management without adverse consequences. Physical fitness with regular exercise and healthy dietary habits can significantly decrease side effects of cancer treatments and may prolong survival. Botanical extracts and vitamin supplements may interfere with active cancer treatments, and should be discussed with the oncologist or pharmacist before use.

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

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.