VOLUME

23

NUMBER

12

APRIL

20

2005

JOURNAL OF CLINICAL ONCOLOGY

High Prevalence of Complementary and Alternative Medicine Use Among Cancer Patients: Implications for Research and Clinical Care
Barrie R. Cassileth and Andrew J. Vickers, Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY

In this issue, Hyodo et al1 report that herbs and other dietary supplements are used by substantial numbers of cancer patients in Japan 44.6% of 3,100 patients, as opposed to 25.5% of 361 noncancer (benign tumor) patients surveyed. These data are consistent with results from numerous prior surveys on complementary and alternative medicine (CAM) use in oncology. A 1998 systematic review examined 26 surveys of cancer patients from 13 countries and reported an average prevalence of 31%, with rates ranging up to 64%.2 Subsequent studies report even higher prevalence, depending on the denition of CAM used.3,4 Reports of prevalence often are exaggerated because surveyors include many aspects of life, such as spirituality, attention to diet, and routine self-care, that from our perspective are not complementary therapies. Nonetheless, use of complementary therapies by cancer patients is substantial. Virtually all studies conducted internationally, such as that reported here, indicate that people who seek complementary therapies are better educated, of higher socioeconomic status, and more likely to be female and younger than those who do not. Data from Hyodo et al1 show that herbs and supplements, which are directed primarily at cancer control, are used much more commonly in Japan than are the symptom management complementary therapies more typically sought in North America. This difference is also of interest because, despite some promising agents, most herbs and other supplements as currently available are of questionable value,5-7 whereas substantial evidence from randomized trials supports the use of complementary therapies for symptom control in patients with cancer, including acupuncture,8,9 massage,10 music therapy,11 and relaxation techniques.12
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In the survey by Hyodo et al,1 more than 96% of patients used Chinese herbs, mushrooms, shark cartilage, vitamins, and so on (Table 3 of Hyodo et al 1). Not mentioned in this article, however, are Japans Kampo products, which are based on traditional Chinese herbal formulas. Kampo botanicals are produced at a pharmaceutical grade, available in pharmacies by prescription, and commonly prescribed by physicians in Japan. This survey excluded Kampo products, explicitly dening CAM as remedies used without the approval of relevant government authorities and not covered by health insurance. Many Kampo products, conversely, are approved by the Japanese government and are covered by health insurance. Essentially, they are high-quality, standardized, government-regulated versions of herbal medicines, which in the West are termed dietary supplements. In North America, however, dietary supplements do not meet the same standards as do the governmentregulated Kampo products in Japan. Ours are poorly standardized, often contaminated, usually not evidence based, and unregulated, and may be dangerous in the oncology setting. Herbs and other supplements are not required to meet standards of safety, efcacy, and consistency, and their use has important implications for clinical care. The continuing availability of such products in the United States results in large part from the 1994 Dietary Supplement and Health Education Act, which created a protective new category for the approximately 20,000 vitamins, minerals, herbs, and other agents sold as supplements before October 1994. Spurred by supplement industry lobbying, the act protects supplements from government scrutiny and mandates that the US Food and Drug Administration prove harm before distribution of a product can be regulated.
Journal of Clinical Oncology, Vol 23, No 12 (April 20), 2005: pp 2590-2592 DOI: 10.1200/JCO.2005.11.922

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Editorial

Problems with highly publicized products such as ephedrine, which was associated with serious toxicities, and PC-SPES, an herbal compound used for prostate cancer, which was found to be contaminated with pharmaceuticals,13 are perhaps the best-known consequences of such limited regulation. This is doubly unfortunate because ephedra is a valuable herb from which pseudoephedrine (Sudafed) is derived. Similarly, PC-SPES was found to be contaminated with diethylstilbestrol, as well as a tranquilizer and anti-inammatory drugs. It was forced off the market despite showing efcacy in clinical trials.14 Perhaps of greatest concern, it is now clear that herbs and other supplements may interfere with conventional oncologic management via metabolic interaction15 or by antioxidant-related protection of tumor cells from oxidative damage.16,17 Accordingly, patients in our institution are advised to avoid the use of herbs and of supplements greater than the recommended daily allowance during and for a week before radiotherapy and chemotherapy. Medicinal mushrooms, the most commonly used product in the survey by Hyodo et al,1 are popular worldwide, and are commonly prescribed in Japan. Moreover, data from controlled clinical trials suggest that they may very well be benecial.18-20 For example, a randomized trial of 462 colorectal cancer patients receiving curative resection compared adjuvant chemotherapy (mitomycin and uorouracil) alone to chemotherapy plus PSK, an extract from the fungus Coriolus versicolor. Both disease-free and overall survival were signicantly higher in the PSK group (3-year survival probabilities of 77% v 68% and 86% v 79%).20 Many researchers, predominantly in the United States, are working on these issues. We now know that medicinal mushrooms contain a class of polysaccharides known as beta-glucans ( -glucans), and that these promote antitumor immunity related to antibody-Fc interactions by activating complement receptor 3.21 This suggests that -glucans might act synergistically with therapeutic antibodies such as trastuzumab or rituximab, an effect already demonstrated in the mouse model.22 Different -glucan products have been compared in laboratory studies to select an agent for clinical study,23 and phase I clinical trials currently are underway to dene dosing. Investigators also have begun to understand the putative immune-enhancing effects of medicinal mushrooms in terms of their effects on growth and differentiation of bone marrow cells.23 The use of the term complementary and alternative medicine by Hyodo et al1 raises the issue of language. Their survey respondents were not using alternative therapies, given that patients were recruited from mainstream cancer clinics. Similarly, only a minority were using the sort of complementary therapies, such as massage or acupuncture, available at U.S. cancer centers. We have proposed the term integrative oncology,24 a synthesis of the best of cancer
www.jco.org

treatment and evidence-based, supportive complementary modalities that effectively relieve many of the physical and emotional symptoms that cancer patients experience.25 Centers such as Memorial Sloan-Kettering, DanaFarber, University of California at several sites, M.D. Anderson, and many more now have programs that clinically integrate conventional and complementary medicine. They also conduct research on complementary therapies and on herbs and other supplements. By bringing these issues into mainstream practice and researchrejecting useless treatments, offering those of proven value, and systematically developing those that show promisewe can emulate Japans regulatory efforts and ensure that the phenomenon described by Hyodo et al,1 common in the Western world as well, becomes a force for the greater well-being of cancer patients.

Authors Disclosures of Potential Conicts of Interest The authors indicated no potential conicts of interest.
2005 by American Society of Clinical Oncology REFERENCES
1. Hyodo I, Amano N, Eguchi K, et al: Nationwide survey on complementary and alternative medicine in cancer patients in Japan. J Clin Oncol 23:2645-2654, 2005 2. Ernst E, Cassileth BR: The prevalence of complementary/alternative medicine in cancer: A systematic review. Cancer 83:777-782, 1998 3. Navo MA, Phan J, Vaughan C, et al: An assessment of the utilization of complementary and alternative medication in women with gynecologic or breast malignancies. J Clin Oncol 22:671-677, 2004 4. Shen J, Andersen R, Albert PS, et al: Use of complementary/alternative therapies by women with advanced-stage breast cancer. BMC Complement Altern Med 2:8, 2002 5. DeVere White RW, Hackman RM, Soares SE, et al: Effects of a mushroom mycelium extract on the treatment of prostate cancer. Urology 60:640-644, 2002 6. Lesperance ML, Olivotto IA, Forde N, et al: Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: An historical cohort study. Breast Cancer Res Treat 76:137-143, 2002 7. Miller DR, Anderson GT, Stark JJ, et al: Phase I/II trial of the safety and efcacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 16:3649-3655, 1998 8. Alimi D, Rubino C, Pichard-Leandri E, et al: Analgesic effect of auricular acupuncture for cancer pain: A randomized, blinded, controlled trial. J Clin Oncol 21:4120-4126, 2003 9. Shen J, Wenger N, Glaspy J, et al: Electroacupuncture for control of myeloablative chemotherapy-induced emesis: A randomized controlled trial. JAMA 284:2755-2761, 2000 10. Grealish L, Lomasney A, Whiteman B: Foot massage: A nursing intervention to modify the distressing symptoms of pain and nausea in patients hospitalized with cancer. Cancer Nurs 23:237-243, 2000 11. Cassileth BR, Vickers AJ, Magill LA: Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: A randomized controlled trial. Cancer 98:2723-2729, 2003 12. Syrjala KL, Donaldson GW, Davis MW, et al: Relaxation and imagery and cognitive-behavioral training reduce pain during cancer treatment: A controlled clinical trial. Pain 63:189-198, 1995 13. Kosty MP: PC-SPES: Hope or hype? J Clin Oncol 22:3657-3659, 2004 14. Oh WK, Kantoff PW, Weinberg V, et al: Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. J Clin Oncol 22:3705-3712, 2004

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15. Mathijssen RH, Verweij J, de Bruijn P, et al: Effects of St. Johns wort on irinotecan metabolism. J Natl Cancer Inst 94:1247-1249, 2002 16. Labriola D, Livingston R: Possible interactions between dietary antioxidants and chemotherapy. Oncology (Huntingt) 13:1003-1008, 1999 17. Memorial Sloan-Kettering Cancer Center: Information Resource: About Herbs, Botanicals, & Other Products, 2004. http://www.mskcc.org/aboutherbs 18. Matsui Y, Uhara J, Satoi S, et al: Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: A prospective cohort study. J Hepatol 37:78-86, 2002 19. Nakazato H, Koike A, Saji S, et al: Efcacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer: Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet 343:1122-1126, 1994 20. Mitomi T, Tsuchiya S, Iijima N, et al: Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer: The Cooperative Study Group of Surgical Adjuvant Immunochemo-

therapy for Cancer of Colon and Rectum (Kanagawa). Dis Colon Rectum 35:123-130, 1992 21. Yan J, Vetvicka V, Xia Y, et al: Beta-glucan, a specic biologic response modier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18). J Immunol 163:3045-3052, 1999 22. Cheung NK, Modak S, Vickers A, et al: Orally administered betaglucans enhance anti-tumor effects of monoclonal antibodies. Cancer Immunol Immunother 51:557-564, 2002 23. Lin H, She YH, Cassileth BR, et al: Maitake beta-glucan MD-fraction enhances bone marrow colony formation and reduces doxorubicin toxicity in vitro. Int Immunopharmacol 4:91-99, 2004 24. Society for Integrative Oncology. http://www.integrativeonc.org 25. Cassileth BR, Deng G, Vickers AJ, et al: Integrative Oncology: Complementary therapies in cancer care. Hamilton, Ontario, Canada, BC Decker, 2005

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