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ORIGINAL PAPER |
Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Correspondence: Barrie R. Cassileth, Ph.D., Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, H13, New York, New York 10021, USA. Telephone: 212-639-8629; Fax: 212-794-5851; e-mail: Cassileth{at}mskcc.org
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LEARNING OBJECTIVES
Top
Learning Objectives
Abstract
Introduction
Therapies
Implications for Oncologists
References
After completing this course, the reader will be able to:
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ABSTRACT |
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Key Words. Cancer • Alternative medicine • Complementary therapies • Herbs • Dietary supplements
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INTRODUCTION |
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We have long promoted what we see as a necessary distinction between complementary and alternative therapies, despite the acronymic convenience, and the viability of a newer term, integrative oncology. Complementary therapies are used as adjuncts to mainstream cancer care. They are supportive measures that control symptoms, enhance well-being, and contribute to overall patient care. Alternative therapies typically are promoted for use instead of mainstream treatment. This is especially problematic in oncology, when delayed treatment can diminish the possibility of remission and cure. Moreover, interventions sold as literal alternatives to chemotherapy, surgery, and radiation therapy tend to be biologically active, potentially harmful, and extremely costly. Over time, some complementary therapies are proven safe and effective. These become integrated into mainstream care, producing integrative oncology, a synthesis of the best of mainstream cancer treatment and rational, data-based, adjunctive complementary therapies. Such integration is evolving. The very term applied to the program at the Memorial Sloan-Kettering Cancer Center (Integrative Medicine Service) and similar titles applied to related programs in North America, the United Kingdom, and Europe, suggest that complementary therapies are being brought into mainstream medicine, including cancer care. Integration varies from country to country, as does the quality of therapies offered.
CAM Users
The use of CAM for cancer is widespread. By various accounts, from less than 10% to more than 60% of cancer patients have used CAM [1–5]. The Datamonitor 2002 Survey indicated that 80% of cancer patients used an alternative or complementary modality [6].
Virtually all studies conducted to date of cancer patients and of the general public internationally show that those who seek CAM therapies tend to be better educated, of higher socioeconomic status, female, and younger than those who do not. Typically, they are more health conscious and utilize more mainstream medical services than do people who do not use CAM. There is some indication of growth in CAM use by cancer patients in recent years [7]. It is likely that this reflects expanded numbers of over-the-counter remedies as well as their ready availability. A recent study found the three most commonly used therapies to be spiritual healing or prayer (13.7%), herbal medicine (9.6%), and chiropractic therapies (7.6%) [8]. Although, in some cases, use of CAM was seen as a marker of greater psychosocial distress and poorer quality of life [9, 10], patients say they use CAM to improve physiologic and psychosocial well-being, because they value the closer relationships possible with CAM practitioners, and because they want more control and greater responsibility for self-care [11].
CAM Practitioners
Major categories of CAM practitioners outside of mainstream medicine include chiropractors, naturopaths, and acupuncturists. Acupuncturists often practice a broader range of traditional Chinese medicine involving herbal remedies [12–14]. The professions of massage therapy, music therapy, and mind-body therapies also have skilled practitioners [15].
Chiropractors, naturopathic doctors, and acupuncturists must complete several years of training and pass standardized national examinations in order to practice in the states that license these practitioners [16–18]. Many states allow physicians to practice acupuncture with little or no training, although states increasingly require national accreditation and an associated specified length of training [18]. An organization representing only acupuncturists with a medical doctor (M.D.) or doctor of osteopathy (D.O.) license was founded in 1987. This organization, the American Academy of Medical Acupuncture, has grown to more than 1,600 members. The National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM), based in Washington, DC, has certified more than 13,000 practitioners since its inception [19].
At the institutional level, numerous hospitals and medical centers have developed research and programs in CAM. Cancer programs as well as many comprehensive cancer centers have or are creating programs of varying complexity. A 1999 survey of 26 National Cancer Institute (NCI)-designated centers showed that 88% had a CAM practitioner and 54% offered CAM programs, the most common being support groups, guided imagery, and nutritional counseling [20].
Economic Impact
The economic impact of CAM is enormous. It was estimated that visits to CAM practitioners increased from 427 million in 1990 to 629 million in 1997, exceeding visits to all U.S. primary care physicians [5]. These 1997 data back a conservative estimate of total U.S. out-of-pocket CAM expenditure of $27.0 billion, with $12.2 billion spent on CAM professional services.
The profound influence of 1994 legislation allowing herbal medicines and other "food supplements" to be sold over the counter without U.S. Food and Drug Administration (FDA) review is evident in the increased use of herbal remedies from 3% in 1991 to over 20% in 1999 [21]. It is estimated that sales of dietary supplements have more than doubled since the passage of the 1994 law. Sale of the five major categories of dietary supplements reached $15 billion in 2000 [22]. A lobbying effort is under way to provide more government protection concerning the safety and efficacy of these readily available products, many of which are contaminated or dangerous (see later sections of this chapter). The food supplement industry continues to oppose these efforts.
Information about CAM is readily available on the internet. The keywords "alternative cancer medicine" searched for on Google.com produced close to 900,000 hits. It is difficult, if not impossible, for most readers to distinguish between reputable sources of information and promotions of unproven alternatives pushed by vested interests.
Reflecting public interest in CAM and the need for vigorous research in this area, appropriations to the NCCAM rose from $2 million in 1992 to $50 million in 1999 and to $114 million for fiscal year 2003. Other governmental agencies, including the NCI, as well as private foundations, also support CAM research.
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THERAPIES |
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Traditional Medical Systems
These complete systems of theory and practice were developed by ancient cultures and remain essentially intact. Prominent examples include traditional Chinese medicine (TCM), India’s ayurvedic medicine, homeopathy, and naturopathic medicine [23]. A common feature across alternative medical systems is an emphasis on working with internal natural forces to achieve a harmonic state of mind and body. Although this concept has great appeal to many members of the general public, the underlying assumptions concerning human physiology and disease are outmoded and inconsistent with current scientific understanding.
Traditional Chinese Medicine
TCM views people as ecosystems in miniature. Any imbalance between opposing forces, such as yin-yang, heat-cold, dampness-dryness, or disruption in the circulation of Chi or Qi, meaning life energy or vital force, produces illness. Maintaining the balance and the flow of "life elements," therefore, is essential to the maintenance or restoration of health.
Diagnostic techniques include examination of complexion and tongue coating, detection of distinctive scents in bodily materials, and palpation of the radial pulse for its speed and tactile characteristics. This information is matched to specific patterns of signs and symptoms to provide a TCM diagnosis (e.g., dampness of spleen). Treatment is then geared to correcting imbalances or disruptions, primarily with herbal formulas or acupuncture.
Hundreds of botanical, animal, and mineral preparations were categorized in traditional Chinese pharmacopoeias starting millennia ago. Approximately 140 biologically active compounds have been isolated from medicinal plants [24]. Among anticancer agents, camptothecin, paclitaxel, vincristine, and indirubin are developed from Camptotheca acuminata, Taxus chinensis, Catharanthus roseus, and Baphicacanthus cusia, respectively, although the original plants were not used traditionally to treat cancer.
Ayurveda
The term ayurveda comes from the Sanskrit words ayur (life) and veda (knowledge). Ayurveda’s ancient healing techniques are based on the classification of people into one of three predominant body types. There are specific remedies for disease, and regimens to promote health, for each body type. This medical system has a strong mind-body component, stressing the need to keep consciousness in balance. It uses techniques such as yoga and meditation to do so. Ayurveda also emphasizes regular detoxification and cleansing through all bodily orifices.
Homeopathy
Homeopathy, or homeopathic medicine, originated in 18th century Germany before the advent of modern medicine. It was based on the concept of similia principle or "like cures like," and the concept of "potentiation," or serial dilution and vigorous shaking of a substance to extract its vital essence. The body’s own healing process is believed to be stimulated by these highly diluted substances derived from plants, minerals, or animals.
Homeopathic remedies are available over the counter without prescriptions. If a claim were to state that a homeopathic remedy could treat a serious disease, such as cancer, by U.S. law, it could be sold by prescription only [25]. However, efficacy is unlikely due to the extreme dilution of active ingredients in homeopathy, which eventuates in less than one molecule of the original substance, meaning that there is nothing in the solution [26]. Systematic reviews and meta-analyses of homeopathy clinical trials show no definitive proof that homeopathic remedies are effective for any medical condition [27–29].
Naturopathy
Naturopathy, or naturopathic medicine, is an alternative medical system that relies exclusively on "natural" healing approaches (such as herbs, nutrition, and movement or manipulation of the body). It is based on the belief that the body will repair itself and recover from illness spontaneously once a healthy internal environment is achieved. Many remedies in naturopathy, for example, mistletoe, saw palmetto, red clover, wheat grass, and flax seed oil, overlap with those in other categories of CAM; they are reviewed in their respective sections.
Questionable Alternative Therapies
Diet and Vitamin Cancer "Cures"
Advocates of dietary cancer treatments typically extend mainstream assumptions about the protective effects of fruits, vegetables, fiber, and avoidance of excessive dietary fat in reducing cancer risk to the idea that foods or vitamins can cure cancer. Current examples include the no-dairy diet, the macrobiotic diet, fruit and vegetable cures, and metabolic therapies, offered in Tijuana, Mexico clinics. One of the best known sites for this questionable practice is the Gerson Clinic, where liver damage is counteracted with a low-salt, high-potassium diet, coffee enemas, and a gallon of fruit and vegetable juice daily [30]. Its use of oral crude liver extract was associated with repeated cases of bacterial contamination [31], although the Gerson.org website (as of 10-01-03) includes "injectable crude liver extract" among its "medications." Other clinics and practitioners provide their own versions of metabolic therapy, each applying an individualized diet plus vitamins, minerals, enzymes, and detoxification regimens, which typically involve multiple "colonic cleansing" procedures.
Modern variations on the older approach to internal cleansing are drinkable cleansing formulas, said to detoxify and rejuvenate the body. These products tend to function as major laxatives, potentially dangerous when taken over days or weeks or on a regular basis as recommended by promoters, especially for cancer patients. Neither the presence of toxins nor the benefit of eliminating them has been documented.
The macrobiotic diet was developed in the 1930s by George Ohsawa, a Japanese philosopher who sought to integrate traditional oriental medicine, Christian teachings, and aspects of Western medicine [32, 33]. This is essentially a vegetarian diet, with emphasis on whole grains, legumes, fresh vegetables, and the occasional intake of fish. The main macrobiotics web site is extremely persuasive and attractive, which probably contributes to an apparent resurgence of interest in this dietary fad (http://www.kushiinstitute.org). The selection of foods is so limited that people on this diet may develop significant nutritional deficiencies. Although healthful nutrition is important for patients and has value in cancer prevention, neither this nor any other diet alone has been shown to cure cancer.
Some patients and alternative practitioners believe that large dosages of vitamins or intravenous infusions of high-dose vitamin C can cure disease. In 1968, Nobel Laureate Linus Pauling coined the term "orthomolecular" to describe the treatment of disease with large quantities of nutrients. His claims that massive doses of vitamin C could cure cancer were not confirmed by clinical trials [34, 35], but megavitamin and orthomolecular therapy, the latter adding minerals and other nutrients, remain popular. Perhaps the simplicity of this approach and the fact that patients can prescribe and obtain their own over-the-counter therapy contribute to its appeal. However, megavitamin or orthomolecular therapy has not been proven to be an effective cancer treatment.
Energy Therapies
Energy therapies are based on the theory that there are energy fields around the human body. It is believed that by changing the purported energy field by manual manipulations, such as Qigong or therapeutic touch, or the application of electromagnetic fields, disease can be eliminated. The existence of such energy fields has not been scientifically proven.
Therapeutic touch (TT), despite its name, involves no direct contact. Instead, healers move their hands a few inches above a patient’s body and sweep away "blockages" to the patient’s energy field. Although a study published in the Journal of the American Medical Association showed that experienced TT practitioners were unable to detect the investigator’s "energy field" [36] and despite mainstream scientists’ unwillingness to accept its fundamental premises, TT is taught in North American nursing schools and widely practiced by nurses in the U.S. and other countries [37].
TT healers in many areas of the U.S. claim the ability to cure people of cancer. Although their ministrations may cause only minor difficulties when patients also receive mainstream care, many patients are firmly convinced of these healers’ abilities and decline even to have tumors removed surgically [38].
Bioelectromagnetic field therapies involve the use of pulsed, alternating or direct current and magnetic fields to treat medical conditions. Clinical trials have been conducted to test magnetic field therapies in managing pain [39, 40], tremor [41], epilepsy [42], and migraine headaches [43]. No data support their role in any illness.
Biologic Treatments
Because this group of alternative treatments is invasive and biologically active, it is highly controversial. One such therapy is antineoplastons, developed by Stanislaw Burzynski in his clinic in Houston, Texas [44]. A joint research effort by the NIH Office of Alternative Medicine and the NCI failed to accrue sufficient numbers of patients, and none of the six patients assessable for response showed tumor regression [45]. Further research at the Burzynski Institute was permitted under an Investigational New Drug permit [46]. The group’s preliminary report from a single-arm phase II study of 12 patients showed a 50% response rate [46]. Researchers at the NCI and elsewhere continue to investigate phenylacetate, a metabolite of the amino acid phenylalanine, which makes up 80% of antineoplastons [47, 48].
Immuno-augmentation therapy (IAT), subcutaneous injections of sera derived from the blood of healthy donors, was developed by the late Lawrence Burton and offered in his clinic in the Bahamas. Burton claimed that IAT was particularly effective in treating mesothelioma [49]. Documentation of IAT’s efficacy remains anecdotal. The clinic has continued to operate following Burton’s death, but its popularity seems to have waned [50].
Advocates of shark cartilage as a cancer therapy base their therapy on its putative antiangiogenic properties [51]. A phase I/II trial of shark cartilage found no clinical benefit [52]. Neovastat, another cartilage extract, was associated with a survival benefit in renal cell carcinoma in higher versus lower doses [53]. However, that trial was not randomized. Two large NIH-sponsored phase III trials were recently initiated [54].
Many additional unproven methods, such as Laetrile [55, 56], bioresonance therapy, oxygen and ozone therapies, insulin potentiation therapy, and many more [26], are promoted as literal alternatives to mainstream cancer treatment. Their popularities wax and wane over time.
Dietary Supplements and Herbal Remedies
Cancer patients use over-the-counter dietary supplements in addition to or instead of other cancer treatments. Preliminary data from the Women’s Healthy Eating and Living study showed that up to 80% of non-stage IV breast cancer patients took dietary supplements such as vitamins, antioxidants, and herbs [57, 58]. An important trend is the increased use of herbal products instead of other supplements in recent years [58]. Systematic, evidence-based information on popular dietary supplements used by cancer patients and herb-drug interactions in oncology is available to consumers and health care professionals [26, 59].
The general public tends not to be aware that herbs are dilute natural drugs that contain scores of different chemicals, most of which have not been documented [60]. Their effects are not always predictable [61]. Neither the FDA nor any other agency examines herbal remedies for safety and effectiveness. Few products have been formally tested for side effects or quality control. Patients undergoing active treatment should be told to stop using herbal remedies, because some herbs cause problematic interactions with chemotherapeutic agents, sensitization of the skin to radiation therapy, dangerous blood pressure swings, and other unwanted interactions with anesthetics during surgery [62].
Herbs such as feverfew, garlic, ginger, and ginkgo have anticoagulant effects and should be avoided by patients on coumadin, heparin, aspirin, and related agents. Concerns have been raised recently even about dietary antioxidants, which may interact with radiation therapy or chemotherapeutic agents [63]. The risk of herb-drug interactions appears to be greatest for patients with kidney or liver problems [64, 65].
Essiac, one of the most popular herbal alternative cancer medicines in North America, was developed initially by a Native healer from southwestern Canada. It was popularized in the 1920s by a Canadian nurse, and comprises four herbs: burdock, turkey rhubarb, sorrel, and slippery elm. Evidence of anticancer activity has been limited to anecdotal reports [66]. No clinical studies support the use of essiac (also sold as flor-essence).
Iscador, a derivative of mistletoe, is a popular cancer remedy in Europe, where it is said to have been in continuous use as a folk treatment since the time of the Druids. Iscador is available in many mainstream European cancer clinics. European governments have funded studies of the effectiveness of iscador against cancer. The results are mixed, with all studies suffering some methodological shortcomings [67]. None of the methodologically stronger trials showed efficacy in survival, according to another systematic review [68].
Several mushroom-derived compounds are approved for use as cancer treatments in Japan. Trials on polysaccharide Kureha (PSK), an extract of the mushroom Coriolus versicolor, showed superior survival with PSK compared with controls in both gastrectomy [69, 70] and esophagectomy patients [71]. Two randomized trials of PSK given after curative resection for colorectal cancer showed that both disease-free and overall survival rates were significantly higher in the PSK group [72, 73]. Results were less encouraging in breast cancer [74, 75] and leukemia [76]. The proposed mechanism was immune modulation. Interestingly, an association between response to PSK treatment and HLA type was reported [77].
A combination of eight herbs, all but two from TCM, PC-SPES (PC for prostate cancer; spes is the Latin word for hope) reduced prostate-specific antigen levels in men with advanced prostate cancer regardless of whether their disease was androgen dependent [78–81]. Improvements in quality of life also have been reported [82]. Estrogenic side effects occurred with PC-SPES, and its mechanism of action, although uncertain, may relate to its phytoestrogenic effects. PC-SPES was suspended from the market in early 2002 when undisclosed contamination with anxiolytic and antithrombotic agents was uncovered [83].
Helpful Complementary Therapies
Mind-body interventions aim to utilize the reciprocal relationship between body and mind to help patients relax, reduce stress, and relieve symptoms associated with cancer and cancer treatments. Hypnosis and relaxation techniques are often used by conventional practitioners, such as clinical psychologists. Several randomized trials have shown effects of hypnosis on both procedural and malignant pain [84, 85] and on anxiety, depression, and mood in newly diagnosed cancer patients [86–88]. Trials also have generally found hypnosis and relaxation training to be beneficial against chemotherapy-induced nausea in adults [89, 90], although some studies found no differences between groups [91].
Music therapy is provided by professional musicians who are also trained music therapists. Typically they hold graduate degrees in music therapy and are trained to deal with the psychosocial as well as clinical issues faced by patients and family members. Music therapy is particularly effective in the palliative care setting, with randomized trials indicating benefit for reducing anxiety [92–96], depression [97–99], and pain [100, 101].
The benefits of massage therapy are documented, especially for seriously ill and palliative care patients. Several randomized trials suggest that massage reduces anxiety, at least in the short-term, in groups as varied as adolescent psychiatric patients [102] and elderly people in care homes [103]. In a high-quality, if underpowered, trial, 35 patients were randomized to receive either up to nine 20-minute massages during inpatient stays or standard care (control). Massage was superior to the control treatment in reducing anxiety, nausea, and fatigue and improving general well-being [104]. In the largest study to date, 87 hospitalized cancer patients were randomized to receive either foot massage or a control treatment. Pain and anxiety scores were lower with massage, with differences between groups achieving both statistical and clinical significance [105].
Acupuncture is the stimulation of certain points along "meridians" on the body by needle (acupuncture), pressure (acupressure), or heat (moxibustion). Modern versions include electrical pulses (electro-acupuncture) or laser (laser acupuncture) to provide extra stimulation [106]. Stimulation is thought to regulate the flow of Qi. The biological basis of Qi or of meridian channels has not been found, but modern research suggests that the effect of acupuncture may be mediated by the release of neurotransmitters [107–109]. Data from clinical trials support the use of acupuncture for emesis [110–112] and pain [113–118]. The NIH issued a concensus statement in 1997 supporting the efficacy of acupuncture for adult postoperative and chemotherapy-associated nausea and vomiting, and for postoperative dental pain [119].
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IMPLICATIONS FOR ONCOLOGISTS |
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Patients should be advised to avoid questionable alternative therapies in a receptive, evidence-based atmosphere. Many unproven alternatives are promoted in a very appealing and convincing fashion. Brushing the topic aside categorically without open discussion may not dissuade patients’ use.
On the other hand, complementary therapies that help manage pain, nausea, fatigue, anxiety, and other symptoms should be integrated into the patient’s overall care. In some cases, patients feel that problems they perceive as important fail to receive sufficient attention. Complementary therapies improve patients’ qualities of life, patient satisfaction, and the physician-patient relationship.
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