Abeloff's Clinical Oncology, 4th Edition

Part I – Science of Clinical Oncology

Section D – Preventing and Treating Cancer

Chapter 35 – Complementary and Alternative Medicine

James M. Metz,Heather Jones




Complementary and alternative medicine (CAM) therapies are used by a significant number of cancer patients worldwide.



Providing a nonthreatening environment for discussion of CAM will facilitate communication on this topic between physicians and patients.



Many types of CAM may interact with conventional medications or cancer treatments to increase the toxicity or decrease the efficacy of the drug or therapy.



Some CAM therapies have been shown to have side effects that mimic those of conventional cancer treatments.



Physicians must warn patients about potential problems with CAM. They also should support those patients using those types of CAM that do not adversely affect conventional cancer treatment.



A number of complementary therapies may be effective for stress reduction and combating pain or nausea.



Health care providers must familiarize themselves with the most common CAM treatments used by patients with cancer so that informed discussions can occur.


Complementary and alternative medicine (CAM) has infiltrated mainstream medical practices in recent years, driven mainly by patient desires to obtain these treatments. These therapies have gained increased exposure through television, radio, magazines, books, and the Internet. Most health care professionals have limited formal education on the subject and are unable to provide informed responses to questions about complementary and alternative methods. Patients’ expectations of their health care team have expanded to include open discussions of CAM. They no longer accept labeling all of these CAM treatments by health care providers as ludicrous and unfounded. Numerous interactions with conventional medical therapies have been described in the scientific literature, so there are important medical reasons for physicians to understand the utilization of CAM. Medical professionals must be able to converse intelligently with the patient about CAM practices and to provide information about relevant dangers and hoaxes when appropriate. Health care providers also must learn to accept patients’ use of alternative and complementary techniques so long as such modalities are safe.

Physicians must ask all patients under their care specifically about alternative and complementary medical practices that may be in use. Patients are more likely to discuss their adoption of these techniques openly when the physician provides a nonthreatening environment for discussion. Patients who have cancer are prime consumers and targets for alternative medical therapies. Many feel that they are in a desperate and hopeless situation. Many simply want to regain control over their lives, and use of CAM is an expression of this desire.

This chapter provides a general introduction to the topic of CAM and considers some of the more commonly used CAM therapies. Not every CAM modality in use is covered, because this would be beyond the scope of the discussion; rather, relevant information on commonly used therapies is presented to promote optimal physician-patient interactions whenever CAM treatments are discussed.


The terms alternative medicine and alternative therapy have become popular in recent years but do not accurately reflect or encompass the practices for which they are used. Alternative is the generally accepted term that refers to a diverse assortment of philosophies, theories, diagnostic, preventive, and therapeutic practices not generally viewed as arising from or belonging to the modern Western medical paradigm.[1] Other popular terms are complementary, unconventional, and integrative medicine. Each of these terms attempts to encompass the practice modalities not common to Western medicine. The terms complementary medicine and integrative medicine often are used to acknowledge the combination of these nontraditional treatment modalities with more conventional views and therapeutic approaches. Although some authors prefer to define alternative medicine as treatment approaches not amenable to combination with conventional therapy, [2] [3] several other terms have been used to define this subject: unconventional, unorthodoxnontraditionalholistic, and non-Western.[1]

The National Institutes of Health (NIH) Office of Alternative Medicine established a Panel on Definition and Description, charging it “to establish a definition of the field of complementary and alternative medicine for purposes of identification and research; and to identify factors critical to thorough and unbiased description of CAM systems and practices that would be applicable to both quantitative and qualitative research.”[4] The panel defined complementary and alternative medicine as follows: Complementary and alternative medicine is a broad domain of healing resources that encompasses all health systems, modalities, and practices and their accompanying theories and beliefs, other than those intrinsic to the politically dominant health system of a particular society or culture in a given historical period. CAM includes all such practices and ideas self-defined by their users as preventing or treating illness or promoting health and well-being. Boundaries within CAM and between the CAM domain and the domain of the dominant system are not always sharp or fixed. Box 35-1 presents a list of CAM modalities defined by the NIH.

Box 35-1 




In 1992, the National Institutes of Health (NIH) convened a meeting to discuss the major areas of alternative medicine and to direct future research activities.[1] As part of this meeting, the group defined the following seven fields of alternative therapy:



Alternative systems of medical practice. This field includes “folk” medicine and organized health care systems based on alternative practice. Examples include acupuncture, homeopathy, and naturopathy.



Bioelectromagnetics. Researchers in this field study how living organisms interact with electromagnetic fields. Magnetic field therapy is one example of bioelectromagnetics practice. It most often is used to treat osteoarthritis and nonunion of bone fractures.



Diet and nutrition. This field includes the use of special diets to improve health. Examples include the macrobiotic diet and orthomolecular medicine.



Herbal remedies. This field includes the use of herbs and plants to promote and improve health. Herbal therapy is considered to be the most popular alternative therapy used in the United States. It is used for many conditions.



Manual healing methods. Practitioners use touch and manipulation to promote and improve health. Examples include chiropractic therapy, massage therapy, and therapeutic touch.



Mind-body interventions. This form of therapy uses the interconnectedness of mind and body to improve health. Examples include psychotherapy, meditation, guided imagery, hypnosis, biofeedback, and prayer. Such interventions most commonly are used to treat nausea and vomiting (particularly for anesthesia- or chemotherapy-induced hyperemesis gravidarum) and postoperative dental pain.



Pharmacologic and biologic treatments. This field includes treatment with drugs and vaccines not accepted by mainstream medicine. Examples include the use of shark cartilage, EDTA for chelation therapy (for coronary artery disease), and apiotherapy.

EDTA, ethylenediaminetetra-acetic acid.


Many studies have been performed to identify the utilization patterns of CAM throughout the world. This section addresses the worldwide use of CAM, which can be influenced by demographic factures such as culture, religion, race, geographic location, and gender of the patient. A number of questionnaire studies have suggested that a significant percentage of cancer patients are using CAM. Estimates range from 9% to 64%, depending on the definition of CAM and the cancer patient population studied. [5] [6] [7] [8] [9] [10] Some evidence indicates that the use of these treatments within the general U.S. population increased during the past decade.[11] Also, studies suggest that many patients do not discuss their use of these treatments with their physicians.[8]

Risberg and colleagues evaluated 252 cancer patients in Norway and found a 45% likelihood (i.e., cumulative risk) of using CAM among patients under observation or cancer treatment.[5] Females were much more likely to use these therapies than males. Liu and associates evaluated 100 patients with advanced cancer receiving conventional cancer treatment in China; 64% were found to be using some form of CAM, mainly herbal therapies.[6] Begbie and colleagues evaluated 319 cancer patients in Australia and found that 22% used CAM treatments; 40% of the users did not discuss them with their physicians.[7] Downer and coworkers found that the 16% of 415 patients with cancer surveyed in England used CAM. The typical user of CAM tended to be younger, of higher socioeconomic status, and female.[8]

In the United States, the use of CAM also is prevalent. In a telephone survey of patients with cancer, 452 of 5047 (9%) admitted to using CAM techniques.[9] Mind-body interventions and diet therapies were the most common. A study from the University of Pennsylvania showed that 40% of patients with cancer undergoing radiation therapy were using CAM. However, only 7% admitted to using these therapies during the standard history and physical examination.[11] Only after the addition of a few directed questions regarding use of CAM did a majority of these patients reveal that they were using these therapies. Exercise and prayer were specifically excluded as CAM practices in this study. A recent study of patients with stage I and II breast cancer found that a complementary or alternative medical system was used by 57.3% of the patient population.[10] When exercise therapy was excluded from the analysis, 40% were using CAM. Younger age and increasing income and educational level were predictors of such use. The definition of CAM can vary significantly between studies, which affects the percentage utilization reported, as noted. Clearly, it is important to understand the precise definitions used in each study when comparisons are made.

Very limited information is available concerning the use of CAM therapies in the pediatric oncology population. An interview of the parents of 84 pediatric patients with cancer in The Netherlands found that 26 of 84 children (31%) had used or were using CAM.[12] Among these children, 19 of 26 (73%) had suffered a relapse before using these techniques. Fernandez and associates performed a study of pediatric oncology patients in British Columbia and found that 42% of the 366 respondents used some form of CAM treatment.[13]


A growing body of literature relating cancer prevention and CAM is available to the public. More than 50% of U.S. adults use some type of vitamin, mineral, or other micronutrient supplement.[14] Several studies indicate that users of dietary supplements believe that supplements can prevent or treat chronic diseases, such as cancer and cardiovascular disease, despite limited scientific support for the efficacy of such use. [15] [16] [17] [18] Information about micronutrient supplements is becoming more common in the popular medical literature and is creating increased curiosity and a broader awareness. The explosion of the micronutrient supplement market is compelling physicians to become aware of dietary supplements. Whether or not they are used in clinical practice is a decision for the individual physician. In view of the increasing number of patients who are using micronutrient supplements, however, it is imperative that physicians have a good understanding of this topic ( Box 35-2 ).

Box 35-2 


The complex trend of public awareness of and use of complementary and alternative medicine (CAM) has grown extraordinarily in the past decade. This seemingly insatiable desire for ancient philosophies and approaches to medical care by the general public seems particularly odd because it comes at a time of extraordinary technological and therapeutic advances. The physician should strive to understand what motivates a particular patient to seek CAM therapies before entering into a discussion with a patient—reaching this understanding can be quite challenging. The clinical literature for the most part has done an excellent job in documenting the incidence and patterns of CAM use but often has overlooked the more important question of why patients choose alternative modes of care. This motivation stems from a complex combination of social, cultural, philosophical, and personal factors that often differ among ethnic groups and disease types.

One reason for this phenomenon, no doubt, is the enormous increase in public access to worldwide information available on the Internet and from extensive media coverage. Commercial advertising and continuous exposure through the lay press, ranging from tabloid publications to magazines, medical journals, and books, have vigorously promoted the concepts of disease prevention and healing by unconventional means, striking a responsive (and highly lucrative) chord in a truly global population.

Another reason for the popularity of CAM is the escalating cost of modern allopathic medical care. New technologies have been developed at a record pace, producing many medical, surgical, and diagnostic innovations, most of which are unquestionably improvements but which also are very costly. The expense and the resulting rationing of these new modalities by managed care programs in an attempt to reduce the costs of medical care have placed them out of reach for a considerable segment of the population. The outcome appears to be the creation of a strong public desire for a wide range of CAM modalities to prevent and treat the full scope of human illness.

Other reasons sited for CAM use have included an affinity for a holistic or natural approach to healing, the need to manage side effects, dissatisfaction with the mindset of physicians, and an overall failure of conventional therapies to meet patient needs. Additional insight can be gained by reviewing patient assessments of CAM providers. Patients often praise CAM providers for the ability to define an illness, the amount of time provided for patient visits, continued involvement of the same provider over the course of treatment, and the attention to personality and personal experience. The satisfaction with treatments received often is not contingent on clinical improvement with regard to the presenting complaint.

Many patients are more informed about complementary and alternative therapies than their physicians are, a situation that, in itself, should encourage physicians to learn more about CAM. CAM therapies offer patients “a participatory experience of empowerment, and authenticity, when illness threatens their sense of intactness and relationship to their world.”[*] Understanding what motivates patients may better enable physicians to enter into a dialogue with them and encourage a positive physician-patient relationship.

*  Pappus S, Perlman A: Complementary and alternative medicine: the importance of doctor-patient communication. Med Clin North Am 2002;86:1–10.


Fruits and vegetables appear to be protective against the major cancers.[19] People who eat more fruits and vegetables that are rich in carotenoids or who have higher serum beta-carotene levels have a lower risk of cancer, according to randomized trials in human populations.[20] The antioxidant vitamins—vitamin A and related compounds such as beta-carotene, as well as vitamins C and E—are prominent components of many fruits and vegetables. Conjecture regarding the micronutrients responsible for this beneficial effect has been extensive because the antioxidant vitamins function as scavengers for DNA-damaging, mutagenic oxygen free radicals.

Accumulating epidemiologic evidence suggests that a number of micronutrients may decrease the incidence of cancers of epithelial cell origin. These include vitamin A, vitamin C, vitamin E, and beta-carotene. Dietary deficiency of vitamins A, C, and E has been implicated in the development of cancers of the lung, breast, oropharynx, stomach, bladder, prostate, and colon. [21] [22] [23] [24] [25] [26]Squamous tissues deficient in vitamin A exhibit metaplastic differentiation that can be reversed by administration of vitamin A and related compounds.[27] Additional evidence suggests that diets rich in vitamin A and related compounds not only diminish the risk but also are protective against the development of certain cancers. Whereas vitamin C appears to inhibit the formation of carcinogenic nitrosamines that have been associated with the development of gastric cancer, vitamin E inhibits mutagenesis and cell transformation mainly through its antioxidant function.[28] Nonetheless, the role of vitamins C and E in neoplastic development remains particularly unclear. Although vitamins C and E function as antioxidants, little evidence is available to support any direct role for these vitamins in the inhibition or reversal of neoplastic growth and development.

Several recent studies of dietary supplementation highlight the importance of clinical trials in defining benefit.[29] Both the CARET (beta-carotene and retinol) and the alpha-tocopherol–beta-carotene trials suggest that pharmacologic doses of beta-carotene increase the risk of lung cancer among smokers or those with asbestos exposure. [30] [31] A large, four-arm clinical trial of multiple dietary supplements in 30,000 subjects in Linxian, China, demonstrated no significant effect on cancer incidence. However, those subjects who received a combination of selenium, beta-carotene, and alpha-tocopherol enjoyed statistically significant lower total and gastric cancer–specific mortality rates.[32]

Vitamin D, Calcium, and Selenium

Among the many minerals required for normal tissue development, calcium and selenium have received the most attention with regard to carcinogenesis. Laboratory data, as well as preliminary clinical data, suggest a role for calcium deficiency in the development of colon cancer. In epidemiologic studies, an inverse relationship also has been reported between vitamin E, vitamin D, and calcium supplementation and prostate cancer.[33] In addition, laboratory studies have shown that the active metabolite of vitamin D, 1,25-dihydroxyvitamin D (calcitriol), inhibits growth of both primary cultures of human prostate cancer cells and cancer cell lines; however, the mechanism by which cellular growth is inhibited has not been clearly defined.[34]

Recently, a large randomized trial of more than 1000 patients with a history of polyps showed that daily supplementation with 1.5 g of calcium reduced new adenomatous polyp formation by 20%.[35]

The Nutritional Prevention of Cancer Study by Clark and associates randomized 1312 patients to receive placebo or 200 mg of selenium per day and was designed to evaluate the effect of this supplement on risk of developing new basal cell and squamous cell skin cancers. In the analysis of the primary outcomes, selenium supplementation had no effect on reducing the incidence of these skin cancers. After preliminary analyses showed a reduction in total carcinoma, however, the protocol was modified in 1990 to add total and cancer mortality, as well as the incidence of lung, colon, rectal, and prostate cancers, as secondary endpoints. Analysis of these endpoints revealed a preventive effect for cancers of the lung, prostate, colon, and rectum, but no reduction in risk of breast or bladder cancer.[36]


Soy products are the primary food source for the isoflavone glycosides genistin and daidzin, which are metabolized by colonic microflora to the biologically active aglycones genistein and daidzein. These compounds, along with lignans, are generically named phytoestrogens and have structural similarities to estradiol. Evidence suggests that the consumption of diets rich in soybean products is associated with lower cancer mortality rates, particularly for cancers of the colon, breast, and prostate. [37] [38] [39] [40]

The soy protein Bowman-Birk trypsin inhibitor (BBI), also found in other beans and peas, now in clinical trials, has been shown to suppress carcinogenesis in laboratory animals and in in vitro transformation systems.[40]

It is difficult to study the effects of micronutrient supplementation on the formation of cancers, in view of the inherent complexity of carcinogenesis. Information about the mechanisms of chemopreventive agents that inhibit carcinogenesis is still imperfect. Elucidation of how various dietary components inhibit carcinogenesis will be instrumental in the development of novel dietary chemopreventive agents in the future. Results from large trials such as the Women's Health Initiative Trial and the Selenium and Vitamin E Cancer Prevention Trial (SELECT) will provide a great deal of information regarding the effects of dietary modification and calcium, selenium, vitamin D, and vitamin E supplementation on breast, prostate, and colon cancer.


National Center for Complementary and Alternative Medicine

In 1990, Congress became aware of the rapidly developing interest in CAM in the United States. In 1991, the Office of Alternative Medicine (OAM) was established at the NIH but did not have formal status as a section or subsection. Initially, it was given an annual budget of approximately $2 million. The budget was increased to $20 million by 1997, and the OAM has since been given increased status by being renamed the National Center for Complementary and Alternative Medicine (NCCAM), with an annual budget of $50 million.[41] The charge of the NCCAM is to begin to appraise various CAM products as scientifically as possible through controlled studies. The NCCAM has thus far been slow in reporting results, no doubt at least in part because of the complex nature of conducting meaningful double-blind, clinical trials with CAM products. Numerous studies, however, are now in various stages of completion through the NCCAM and many other facilities throughout the world. At present, 13 institution-affiliated centers of research on CAM exist in the United States, and 75 medical schools in the United States are now teaching integrative medicine courses to their medical students.[41]

Herbal Medicine

Herbs have been used for medicinal purposes for thousands of years. Ancient Egyptians used herbs for the treatment of disease as early as 3000 bc. Almost one fourth of the current pharmacopoeia is derived from botanicals. Digoxin is derived from foxglove, aspirin is derived from willow bark, narcotics are derived from opium poppy, and birth control pills were developed from the Mexican yam. With the advent of modern medical science, people came to believe that synthetic ingredients were more effective than those found in nature, and the use of herbal remedies quickly diminished, especially in the United States. Currently available herbal preparations are sold mainly as nutritional products.[42]

Today, herbs are widely used in Europe and are again gaining popularity in the United States.[43] The most informative longitudinal data on use of herbal medicine derive from two Harvard surveys. [43] [44]The results indicated that between 1990 and 1997, the use of self-prescribed herbal medicines within the U.S. general population increased from 2.5% in 1990 to 12.1% in 1997. During the same period, the proportion of persons consulting practitioners of herbal medicine rose from 10.2% to 15.1%. These survey studies estimated that in 1997, the entire U.S. population spent approximately $5 billion on herbal medicines. Most of this was out-of-pocket expenditure. [43] [44] [45]

Regulation of Herbals

The over-the-counter availability of herbal medicines fosters the notion that these medications are safe, and many casual users have inadequate knowledge about the use of these medications. Users often avoid discussing the use of these medications with their conventional care providers unless specifically asked.[46] These factors may set the stage for potential adverse drug reactions and interactions. Consumers in the United States are accustomed to products that have been tested and approved before sale. The U.S. Food and Drug Administration (FDA) functions to oversee the safety of foods, drugs, and medical devices sold in this country.

Most herbal products in the United States are considered dietary supplements and thus are not regulated as medicines and are not required to meet the standards for drugs specified in the Federal Food, Drug, and Cosmetic Act. In 1994 the Dietary Supplement and Health Education Act (DSHEA) was passed. This legislation had profound effects on the regulation and marketing of herbal products in the United States. Herbs or other botanicals could be sold as dietary supplements and were not subjected to the rigorous regulations that applied to medicines.[47] Herbal products may be produced without the assurance of compliance standards for good manufacturing practice (although such standards are being developed), and they are marketed without previous approval of their efficacy and safety by the FDA. According to the DSHEA, the manufacturer of a herbal preparation is responsible for the truthfulness of claims made on the label and must have evidence that the claims are supported, yet the DSHEA neither provides a standard for the evidence needed nor requires submission of the evidence to the FDA. Under the DSHEA, the manufacturer is permitted to claim that the product affects the structure or function of the body, so long as no claim is made of efficacy for the prevention or treatment of a specific disease, and provided that a disclaimer is supplied informing the user that the FDA has not evaluated the agent. Some of the claims on the labels of herbal products suggest that they can be used to treat disease, and supplementary materials, produced by persons other than the manufacturer, that overtly promote such use may be available where the herbal remedies are sold. According to the DSHEA, the manufacturer is responsible for controlling quality and safety, but if a concern about safety arises, the burden of proof lies not with the manufacturer but with the FDA, which has to prove that the product is unsafe. [48] [49]

Several European countries have implemented guidelines for licensing herbal remedies. In Germany, such products can be registered as medicines on the basis of information in approximately 300 monographs on herbs (“positive” monographs with concise information about terminology, composition, uses, contraindications, side effects, drug interactions, dosage, mode of administration, and actions, and “negative” monographs explaining insufficient benefits or unacceptable risks).[50]

The European Commission (which governs the European Union) has recently publicized a draft directive on the licensing of traditional herbal preparations. If accepted, this proposal will require all members of the European Union to introduce a simplified procedure for these preparations so that they can receive a “traditional use” registration without the need to present data on efficacy from randomized trials. [49] [51] The simplified licensing approach allows a premarketing assessment of the quality and safety of a product and facilitates postmarketing surveillance and product recalls.[49]

Generally, herbal products are not evaluated by the strict preclinical toxicology and pharmacology guidelines that are in place for conventional drugs. Instead, the focus of the clinical trials is on the efficacy of the products. A number of herbal formulations currently are undergoing clinical trials. The FDA has established a hotline for information about herbal products and one for reporting adverse effects.[47]


Acupuncture has been practiced in China for more than 5000 years. Around the same time, acupressure, which uses similar points without needles, was developed in Japan. Acupuncture may be recommended by some practitioners for a variety of conditions, but abatement of pain or of nausea and vomiting is of greatest interest for cancer patients.

Acupuncturists use fine needles that range in length from 0.5cm to several centimeters. The needles, usually made of stainless steel or copper, are placed approximately 5 mm deep and are gently manipulated by hand. The needles may be stimulated with a weak electrical current or by heat. Many patients describe a tingling sensation and feel a sense of heaviness in the area where the needles are placed.

The classic acupuncture teaching states that a life force called qi (pronounced “chi,” to rhyme with “eye”) dominates every organism and flows along interconnected meridians through the body and crosses at specific points. The meridians surface at various locations denoting the acupuncture points (these points are very similar for both acupuncture and acupressure). The opposing forces of yin and yang must be in balance before qi can get the body's vital functions to work normally; imbalance causes an accumulation of lactic acid in the muscles. Stimulating the acupoints dissipates the lactic acid and restores the yin-yang balance and the flow of qi.

To date, scientists in the Western world have found no evidence to support the existence of qiyin, or yang. Bing and colleagues observed that stimulation of acupoints with needles activates the subnucleus reticularis dorsalis neurons that send projections to the dorsal horn of the spinal cord at all levels.[52] These investigators suggest that this anatomic structure may be involved in the modulation of pain. Grossman and Clement-Jones postulated that the release of endorphins within the nervous system may reduce the perception of pain.[53] Of interest, it also has been shown that the acupoints have a similarity in location to some of the anatomic sites used for local and regional anesthesia.[54]

Cancer Pain and Acupuncture

Owing to the widespread use of acupuncture and evolving scientific studies, in 1997, an NIH panel of experts issued a consensus statement for the use of acupuncture. According to this statement, clear evidence supports the effectiveness of acupuncture for the treatment of postoperative and chemotherapy-induced nausea and vomiting, nausea associated with pregnancy, and postoperative dental pain.[55]

In the palliative care setting, acupuncture is increasingly being used alongside conventional medical treatment for pain and symptom management.[56] Select evidence indicates that acupuncture effectively reduces acute perioperative and postoperative pain. [57] [58] [59] [60] Despite numerous observational studies showing the effectiveness of the technique for chronic cancer pain relief, randomized controlled trials (RCTs) of acupuncture remain scarce. A recent review of the published data revealed only a single high-quality RCT for pain control in cancer,[61] by Alimi and colleagues.[62] This study showed statistically significant pain relief with auriculoacupuncture in patients with cancer compared with those in two control groups: a “nonpoint” needling control group and a noninvasive control group. Numerous observational and case series suggest that acupuncture may help relieve a variety of pain symptoms, including postsurgical and treatment-induced breast pain, often resulting in reduction in analgesic requirements and an improvement in mobility and circulation. [63] [64] [65] [66] [67] [68] [69] [70]

Non-Pain Syndromes and Acupuncture

Nausea and vomiting are harrowing symptoms that commonly accompany cancer treatments. Numerous RCTs and reviews have been performed using the traditional point and have shown efficacy for postoperative nausea and vomiting and chemotherapy-related nausea and vomiting. [71] [72] Fatigue is a commonly encountered debilitating symptom in cancer and may persist after successful cancer treatment. [73] [74] A recent study concluded that acupuncture was worthy of further study in the treatment of fatigue following chemotherapy.[75] Studies indicate that pilocarpine-resistant xerostomia can be ameliorated by acupuncture.[76] Vasomotor symptoms and hot flashes secondary to cancer treatment and hormone manipulation also have been ameliorated by acupuncture. [5] [77] [78]

Regulation of Acupuncture

Acupuncturists can be certified in either of two ways: They can complete a formal, full-time educational program that includes both classroom and clinical hours, or they can participate in an apprenticeship program. Acupuncturists also must complete a “clean needle technique” approved course. Medical doctors with training in acupuncture also can obtain board certification. Certification for formally trained acupuncturists is through the National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM). Medical doctors are certified through the American Academy of Medical Acupuncture and must possess a valid medical license. Currently, 37 of the 40 states that regulate acupuncturists require NCCAOM certification.

In response to petitions submitted by the acupuncture community, the FDA has reclassified acupuncture needles for general use from class III, the category in which clinical studies are required to establish safety and efficacy, to class II, a category that involves less stringent control by the FDA but does require good manufacturing and proper labeling. Manufacturers are required to label FDA needles for single use only. Use of acupuncture needles for clinical practice would be restricted to qualified practitioners as determined by state practice laws.[47]


From the Greek words homoios (“like”) and pathos (“suffering”), homeopathy is a system of medicine whose first tenet is the “principle of similars”: A substance that can cause symptoms in a healthy person possibly can encourage self-healing in a person with an illness presenting with similar symptoms. This principle was developed into a practice of medicine in the nineteenth century by the renowned German physician Hahnemann. The theory of homeopathy is rooted in three of Hahnemann's principles: (1) the “law of similars,” which states that a substance that can cause disease in a well person can cure similar symptoms in the diseased; (2) the “principle of the minimum dose,” which states that by diluting a substance, its curative properties are enhanced and its side effects minimized; and (3) prescribing for the individual, which advocates basing treatment not only on the medical diagnosis but also the patient's temperament, personality, and emotional and physical responses.[58]

The principles of homeopathy are not well understood by the public or the medical profession, yet medical consumers are using homeopathic treatments in increasing numbers. In the United States and Europe, the sale of homeopathic medicines increased by 20% to 30% per year in the 1980s and 1990s.[80] A recent survey study revealed that many women who have breast cancer turn to alternative treatments in the hope of minimizing adverse reactions to treatment, rather than in the hope of a cure,[81] and use homeopathy for the reduction of treatment-related side effects. Two reviews identified 11 additional RCTs of homeopathy between 1997 and 2001. [82] [83] These trials did not show any strong evidence that homeopathy was effective for any specific condition, and some of the better-designed trials had the least positive results. Even more recently, a comparative study of 100 placebo-controlled trials of homeopathy and conventional medicine found no specific effect for homeopathy when sources of bias were removed.[84]

Two meta-analyses have been published suggesting that homeopathic remedies are more effective than is placebo alone. However, both studies conclude that the current research and literature in the field do not meet the rigorous, scientific proof needed to establish efficacy of homeopathy for specific clinical conditions. [85] [86] More research is needed before homeopathy can be declared clinically useful for any one condition.

Regulation of Homeopathy

Although in other countries, homeopathic training and certification have been available for decades, the United States has not had full-time homeopathic schools or accredited professional education for more than 40 years.

Only three states—Arizona, Connecticut, and Nevada—license homeopaths. The scope of practice varies but includes the use of substances of animal, vegetable, or mineral origin given in microdoses and prepared according to homeopathic pharmacology. All three states use licensure as a means to authorize practice. These states require a DO or MD degree, as well as certification in the study of homeopathy. Arizona and Nevada have independent examining boards. In Delaware and New Hampshire, the practice of homeopathy is regulated by the state, although under no specific board. The Council of Homeopathic Education has implemented a voluntary certification process that includes a written multiple-choice examination, an oral examination, a videotaped interview, and 10 case reports. A person can be admitted to examination only after completion of a required curriculum and clinical supervision. Thus far, this certification process has not been recognized by the U.S. (or other) medical boards.

The FDA currently is attempting to establish guidelines for the regulation of homeopathic products. The FDA takes the position that homeopathic remedies, which are used in the treatment of disease, are by definition drugs and should be regulated. In recent years, the FDA has exempted homeopathic products from the regular drug-reviewing process if such drugs have been reviewed and approved by the Homeopathic Pharmacopeia of the United States.[47]


Massage therapy has had a long and well-known history, having been known to the ancient Chinese and Japanese and the Greeks, Romans, and Egyptians. The “laying on of hands” was the primary form of healing throughout history in places such as ancient Greece, where Hippocrates wrote that the “physician must be experienced in many things, most especially in rubbing.”[87] Massage therapy is considered a form of medical treatment in several countries where it is covered by national health insurance, including China, Japan, Russia, and West Germany. In the United States, massage therapy still is considered a CAM modality. The popularity of massage therapy is growing. National and international massage therapy associations increased their membership by thousands of therapists during the 1990s.[88]

Regulation and Training for Massage

To become certified, massage therapists must complete a formal therapeutic massage bodywork program. They also may be considered for certification if they have training in anatomy, physiology, and kinesiology, as well as formal education and professional experience in bodywork or massage, or both. Massage provider practice acts for the regulation of massage exist in 22 states. Most statutes include directives for the treatment of soft-tissue or muscle, or both. Techniques may include, but are not limited to, friction, beating, and percussion. Types of health conditions treated, depending on the practice act, include maintaining good health, improving muscle tone, and reducing stress. Board certification is through the National Certification Board for Therapeutic Massage and Bodywork and is required in 20 of the 29 states that regulate massage therapists. [47] [88]

Naturopathic Medicine

Benedict Lust, a German physician, introduced naturopathy to the United States. He used the term naturopathy (from natur, to indicate nature, and pathy, from homeopathy) to encompass all natural approaches to healing. Several healing modalities have been added to the healing module to arrive at modern naturopathy. Naturopathic medicine is far from being a single scientific discipline. The basic principle is that healing comes from within more than from without, and that medicine depends on the healing power of nature to cure ( Table 35-1 ). Naturopathy employs various natural means to empower the patient to reach the ability to self-heal. The tools include lifestyle modifications, nutrition, dietetics, herbs, breathing, education, and hydrotherapy. In addition, naturopaths may elect to use a variety of healing modalities, including acupuncture, botanicals, homeopathy, massage, and Oriental medicine. Naturopaths are the “generalists” of the alternative medicine world. The emphasis of their practice is on prevention, education, and health maintenance.[89]

Table 35-1   -- Six Basic Principles of Naturopathic Medicine


Resultant Principle



The belief that the body has the inherent nature to heal itself



The belief that health and disease result from the interaction of a person's physical, mental, emotional, genetic, environmental, and social components



The belief that the cause of disease, not merely the symptoms, should be treated



The belief that a physician's major role is to educate, empower, and motivate patients to take responsibility for their own health



The healing power of nature underlies the ability to recover from illness or injury.



Treat the whole person.



First, do no harm.



Identify and treat the cause.



Prevention is the best cure.



The physician is a teacher.

Shealy CN, Thomas R (eds): The Complete Family Guide to Alternative Medicine. Rockport, Mass., Element Books, 1996.




Regulation and Training for Naturopathy

Naturopathic practitioners undergo a 4-year training program that includes therapies such as homeopathy, clinical nutrition, manipulation, herbal medicine, and hydrotherapy. Naturopaths often may have additional training in Chinese medicine (acupuncture and herbs). Naturopaths are licensed in 12 states. The naturopathic certification examination is administered by the North American Board of Naturopathic Examiners. Each state defines the scope of practice differently, using several adjunctive therapies including acupuncture, biofeedback, and nonprescription medications. [47] [89]


The term chiropractic is derived from two Greek words meaning “done by hand” and is defined as “the diagnosis, treatment and rehabilitation of conditions that affect the neuromuscular system.”[89]Chiropractic care origins are in the manipulative health care modalities. It became an organized discipline approximately 100 years ago when Canadian Daniel David Palmer introduced it in the United States. The chiropractic system of health is based on two principles: a testable principle, that the structure and condition of the body influence how it functions and heals, and the untestable principle that the mind-body relationship is instrumental in maintaining health and affects the healing processes. Hence, the focus is on the body's ability to self-heal, on the nervous system's role in overall health, and on the interaction between body structure and the functioning of the nervous system. In the past decade, chiropractic care gained measured acceptance and has developed into a treatment and wellness modality that is practiced by 55,000 licensed practitioners and used by roughly 10% of the U.S. population. A majority of visits to chiropractors in the United States are for back pain. According to some studies, chiropractic treatment is as beneficial for low back pain as treatment given by primary care providers, orthopedists, and physical therapists. [90] [91] The evidence for the use of chiropractic for other conditions is less compelling.

Regulation and Training for Chiropractic Care

Chiropractic care is licensed in all 50 states, with 45 requiring insurers to include it in their plans. A large variation exists in the scope of practice; certain states restrict the practice to spinal manipulation, whereas others permit different procedures to be performed, such as acupuncture, electromyography, and laboratory diagnosis. The Council on Chiropractic Education (CCE) (www.cce-usa.org) has accredited 17 colleges of chiropractic medicine in the United States. Since 1974, chiropractic education has been established with a 4-year curriculum monitored by the CCE. Admission requirements differ from school to school, although a minimum of 2 years of college education and specific science courses are required by all. [47] [92] Chiropractors must pass either a state licensing examination or an examination given by the National Board of Chiropractic Examiners.


The word Ayurveda is derived from the Sanskrit ayur, meaning “long life,” and veda, “knowledge.” One of the world's oldest traditional healing systems, Ayurveda has been documented and practiced in India for thousands of years. Ayurveda is a holistic system that deals with all aspects of life: mind, body, and spirit. The ayurvedic practice is founded on the pooled wisdom of ancient Hindu saints and healers. Ancient Ayurveda was meant essentially to promote health, rather than fight disease.

A basic theory of Ayurveda states that everything in the material world is a sign of the unseen universe of energy or life force. The world was created from the unseen universe when the primordial sound created the five fundamental elements responsible for the material world: space, air, fire, water, and earth. These five elements manifest in the human physiology as three life energies called doshas. The three doshas are vata (space and air), pitta (fire and water), and kapha (water and earth). Each dosha, its subdivision, and underlying structures confer a particular characteristic and quality to each person. Health is a state of balance among the mind, body, and consciousness. Several factors can disturb this balance, including congenital and genetic factors, natural tendencies, habits, seasonal factors, and internal and external traumas. The imbalance produced in the doshas disturbs the life force, producing the disease state.

Diagnosis is based on identifying the exact quality and nature of the imbalance and correcting it. This is accomplished through a detailed history, inspection, and examination. Radial pulses (three superficial and three deep pulses, bilaterally) and tongue, nail, and eye examinations, among others, are important parts of the ayurvedic diagnostic examination. Treatment consists of amplifying or reestablishing the body's balance through a combination of interventions, including lifestyle changes, diet modifications, meditation, yoga, breathing exercises, massage, aromatherapy, herbs, and detoxification.[93] Studies have documented the favorable effects of regular meditation on reducing cardiovascular risk factors and stress. Further studies investigating the effects of the ayurvedic herbal products on a wide variety of conditions including cancer, aging, and health promotion are ongoing.[94]

Regulation and Training for Ayurveda

Ayurvedic medicine is the progenitor of several CAM disciplines. These include aromatherapy, homeopathy, and massage. There is no national standardization of training and credentialing of ayurvedic providers. A wide variance of training and experience exists among providers.


The tendency of CAM modalities to change and shift in popularity does not arise in response to new developments or randomized clinical trials; rather, particular therapies simply go in and out of vogue. Typically, a CAM therapy remains popular for a limited period of time, after which it is replaced by a new and usually nonvalidated CAM therapy. Popular CAM modalities that currently are used by cancer patients are discussed in this section under the categories developed by the NIH (see Box 35-1 ).

Mind-Body Techniques

The effectiveness of meditation, biofeedback, and yoga in stress reduction and in the control of particular physiologic reactions is well supported by accepted research. The belief that patients can use mental attributes and mind-body work to prevent or cure cancer has not been demonstrated in clinical studies.


Biofeedback manipulates the body's physiologic responses that are normally controlled by the autonomic nervous system. A biofeedback therapist, of which there are over 10,000 in the United States, can teach a patient how to control many involuntary functions. Some patients learn to control their heart rate, blood pressure, muscle tension, and emotions.

Monitoring electrodes are placed on the body or scalp by the biofeedback therapist. The electrodes then are connected to a computer or polygraph, which will emit a noise or signal indicating the intensity or level of the process to be controlled. The patient is instructed to concentrate on influencing the signal. Specific mental exercises are carried out under the direction of the therapist. The patient is asked to visualize certain images that affect mood and in time may become able to identify which mental exercises change the signals. After a number of sessions (usually 8 to 10), the patient may be able to affect certain of the autonomic processes.

Researchers at Vanderbilt University performed a randomized study to evaluate the effectiveness of a combination of biofeedback and relaxation training for the reduction of side effects of chemotherapy.[95] Biofeedback reduced some indices of physiologic arousal but did not modify the side effects of chemotherapy. However, relaxation training was found to produce a decrease in nausea and anxiety during chemotherapy and a decrease in physiologic arousal after chemotherapy. The researchers concluded that the major benefit of biofeedback was the relaxation training that accompanies the instruction and not the biofeedback alone.

The potential benefit from biofeedback therapy for the cancer patient is relaxation and reduction of stress. This can undoubtedly improve quality of life and allows the cancer patient to take an active role in overall management. Biofeedback is a noninvasive procedure. A group of 10 sessions with a biofeedback therapist costs approximately $500. No specific reports in the medical literature have described side effects attributed to the use of biofeedback.

Guided Imagery

Guided imagery is a technique that relies heavily on the power of suggestion to create relaxing mental images. It is particularly useful for relieving stress and promoting serenity. Some patients find that it helps them cope more effectively with the impact of the diagnosis and the side effects of treatments.

In this technique, the therapist instructs participants to visualize a specific image. Sometimes the participant is asked to visualize a mass of cancerous cells being attacked by the immune system, chemotherapy, or radiation therapy. Many patients use guided imagery audiotapes that provide instruction on meditation exercises, guided relaxation, and visualization techniques. Some patients use these tapes while they are undergoing chemotherapy or radiation therapy, or en route to receive treatment.

Syrjala and colleagues evaluated relaxation and imagery training along with cognitive-behavioral coping skills for control of oral mucositis pain in patients undergoing bone marrow transplantation.[96]These investigators found that patients who received relaxation and imagery training reported less pain than the control groups. No benefit was obtained with the addition of cognitive-behavioral skills, however.

The goal of guided imagery is total relaxation. Patients learn breathing exercises to help them attain an “inner calm,” or they try to modify their experience of anxiety or pain by imagining a pleasurable scene or situation. Some patients with cancer find the method effective in promoting relaxation and relieving anxiety. It must be emphasized, however, that no reliable evidence indicates any effect of this technique on disease progression or survival.

Guided imagery is a noninvasive therapy. Relaxation and guided imagery audiotapes cost approximately $10 to $20 and are available in local bookstores. Some patients prefer to visit a therapist for individualized training, which may be more expensive. No reports in the medical literature describe any side effects related to guided imagery.

Herbal Medicine and Biological Supplements


PC-SPES (PC stands for “prostate cancer,” and SPES is the Latin word for “hope”) is a patented preparation of eight herbs[97] ( Box 35-3 ). PC-SPES is the only herbal medicine for prostate cancer that has been subjected to clinical trials.

Box 35-3 




Dendranthema morifolium Tzvel. (chrysanthemum)



Isatis indigotica



Glycyrrhiza glabra L.



Ganoderma lucidum



Panax pseudo-ginseng



Rabdosia rubescens



Saw palmetto



Scutellaria baicalensis Georgi (skullcap)

Four clinical trials of PC-SPES have been carried out in the United States and Germany. [98] [99] [100] [101] These trials have been single-arm, phase I and II studies in patients with prostate cancer and have demonstrated prolonged decreases in prostate-specific antigen (PSA) levels in most of the men in the study. The side effect profile of PC-SPES has been suggestive of an estrogenic effect (i.e., breast tenderness, decreased libido, impotence, venous thromboses), and components of PC-SPES contain known phytoestrogens.[99]

The largest and most recently reported study was a phase II trial in 70 patients with prostate cancer.[101] Each patient received 320 mg of dried PC-SPES extract orally, three times a day. All androgen-dependent patients experienced PSA declines of 80% or more, and 26 patients (81%) experienced PSA decreases to undetectable levels. At 15 months, only one patient exhibited biochemical or objective progression. More than half of the patients with androgen-independent disease had a PSA response, with a median duration of response of 18 weeks. In the two androgen-dependent patients with positive findings on bone scans at study entry, one patient's follow-up scan revealed complete resolution of the osseous lesions, and the second patient's follow-up scan showed improvement but did not yield normal results. One patient had measurable disease and experienced complete resolution of a bladder mass seen on pelvic CT scan, accompanied by a decline in PSA from 8.9ng/mL to an undetectable level. PC-SPES generally was well tolerated but was associated with a number of endocrine side effects, including decreased libido, erectile dysfunction, gynecomastia or mastodynia, and hot flashes.

Despite these encouraging results, a survival benefit for PC-SPES thus far has not been demonstrated. A worrisome possibility is that PC-SPES may decrease PSA levels while masking increases in tumor growth. PC-SPES also is associated with an increased risk of thromboembolic events. [102] [103] [104] Of enormous concern, PC-SPES was found to contain warfarin (and SPES, a more generic version for all cancers, to contain alprazolam), prompting the U.S. Food and Drug Administration (FDA) to issue a recall of both products in February 2002.[105]

Hydrazine Sulfate

Cachexia remains a major problem in patients with advanced disease undergoing cancer treatment. There has been interest for a number of years in hydrazine sulfate for combating cachexia seen in cancer patients. Gold evaluated 84 patients with disseminated cancer and found that 59 of the 84 patients (70%) improved subjectively and 14 of the 84 (17%) improved objectively when receiving hydrazine sulfate. It was concluded that the compound may favorably influence nutritional status and clinical outcome in patients with disseminated cancer.[106]

Enthusiasm has been dampened by three prospective trials that showed no benefit when hydrazine sulfate was added to standard treatment regimens. Loprinzi and coworkers randomized 243 patients with non-small-cell lung cancer and 127 patients with advanced colorectal cancer to receive hydrazine sulfate or a placebo in addition to conventional anticancer regimems and showed no benefit with use of hydrazine sulfate. [107] [108] Kosty and colleagues randomized 291 patients with advanced non-small-cell lung cancer to receive chemotherapy with or without hydrazine sulfate.[109] No benefit was found for pain control, cachexia, or survival in any of these studies. Hydrazine sulfate is not recommended for the treatment of any cancer-related symptoms, although it remains widely promoted on the Internet.

Shark Cartilage

Shark cartilage has gained increased popularity as the basis for an unconventional medical therapy (UMT) for the treatment and prevention of cancer. Shark cartilage was initially promoted by William Lane, PhD, in his book Sharks Don't Get Cancer and the follow-up book, Sharks Still Don't Get Cancer. In fact, however, tumors, including malignant tumors, do develop in sharks, in which thyroid and central nervous system neoplasms, [110] [111] papillomas, [110] [111] [112] oral cavity cancers, adenomas of the liver, chondromas, and odontomas[110] have been observed.

Shark cartilage is purported to contain angiogenesis inhibitors. In fact, a modest antiangiogenic effect has been seen in vitro.[113] Shark cartilage is supplied in powder and capsule forms. It usually is taken orally but sometimes as an enema.

The television news program 60 Minutes gave shark cartilage a huge boost a few years ago. The program reported a Cuban study of 29 patients with “terminal” cancer who were placed on shark cartilage; most “felt better” several weeks thereafter. “Feeling better” is not a reliable endpoint in a scientific study. The National Cancer Institute (NCI) performed a review of the study and found the data to be “incomplete and unimpressive.”[114] The 60 Minutes program allegedly refused to broadcast the findings of the NCI.

A small study on shark cartilage was reported at the American Society of Clinical Oncology in 1997.[115] Of the 58 patients with advanced cancer who were given shark cartilage for 12 weeks, not one objective complete response or partial response to shark cartilage was obtained. Only two patients reported significant improvement in the quality of life. Rigorous studies of shark cartilage are ongoing at a number of institutions, but no positive results have yet been published. It has been reported that shark cartilage can cause an elevation of values on liver function tests (LFTs) and frank hepatitis.[116]Patients on chemotherapy should be urged not to use shark cartilage enemas because of the risk of infection associated with chemotherapy-associated neutropenia.

Shark cartilage is relatively expensive. If it is taken as described by William Lane, the cost of the 16-week program is approximately $3000.


Mistletoe (Viscum album L.) is one of the most commonly used CAM herbal medicines in Europe. [5] [117] [118] The active compounds identified in mistletoe are lectins (glycoproteins) and viscotoxins (proteins). The lectin component has in vitro immunostimulant activity and has been shown to increase the number of peripheral blood lymphocytes, as well as lymphocyte activity, in patients with gliomas.[119] [120] [121] The viscotoxins have been shown to have direct cytotoxic activity against certain cancer cell lines.[122]

Mistletoe has been used primarily as an adjuvant to conventional cancer therapies to manage micrometastatic disease. Various mistletoe products have been evaluated in several randomized, controlled clinical trials. An analysis of 11 of the randomized trials of mistletoe published in 1994 found that although 10 of these studies reported improved survival in the mistletoe treatment group, many of these trials had deficiencies in 5 or more of the 10 criteria of good methodology. These methodologic issues have led reviewers to question the validity of these studies and promoted demands for further well-defined studies.[123]

Recently, two well-designed prospective randomized trials have reported negative results. The effect of adjuvant treatment with mistletoe lectin-1, a standardized mistletoe preparation (Eurixor), was tested in a prospective, randomized clinical trial involving 477 patients with head and neck squamous cell carcinoma.[124] The European Organization for Research and Treatment of Cancer (EORTC) has completed a phase III randomized trial of adjuvant treatment with low-dose interferon-α versus interferon-γ versus mistletoe extract (Iscador M) versus no further treatment after curative resection of high-risk stage I or IIB malignant melanoma. No benefit was seen in disease-free survival or overall survival for patients receiving either Eurixor or Iscador. [124] [125]

Ginseng (Panax Ginseng)

Ginseng has been touted as enhancing mental and physical strength. It may affect nitric oxide synthesis in the endothelial tissue of the lung, heart, and kidney.[126] In addition, effects on serotonin and dopamine may be responsible for its actions. Survey data indicate that breast cancer survivors seeking treatment for fatigue often turn to this drug for amelioration of fatigue.[127] A recent randomized, double-blind, placebo-controlled pilot trial was carried out by Kim and colleagues. Fifty-three patients were randomly assigned to receive sung ginseng 3000 mg a day or placebo. Quality of life was assessed using the World Health Organization Quality of Life Assessment and the General Health Questionnaire-12. The investigators concluded that ginseng did improve the quality of life scores of patients and that this intervention warranted further investigation.[128]

Adverse effects may include irritability, insomnia, and gastrointestinal disturbance. Ginseng may interact with oral anticoagulants, antiplatelet agents, corticosteroids, and hypoglycemic agents.[129]


Several studies have demonstrated the efficacy of ginger for the treatment of nausea and vomiting. Most of the investigations involved pregnant women. [130] [131] [132] [133] [134] A randomized study of ginger for the amelioration of nausea caused by platinum-based chemotherapy showed that ginger is at least equivalent to the commonly used medication metoclopiramide and has less toxicity.[135]

Hoxsey Regimen and Essiac

The Hoxsey regimen, a herbal compound comprising pokeroot, burdock root, barberry root, buckthorn bark, and stillingia root, was used first in 1924 by Harry Hoxsey. The recipe was passed down to him by his grandfather, a farmer who observed a horse cure itself of cancer by eating certain plants. Despite decades during which no supporting data have been forthcoming, the Hoxsey formula remains popular and in use among patients with cancer.[80]

Essiac is one of the most popular herbal medicines in North America and is a mixture of four herbs given by a Native American healer to nurse Renee Caisse. (“Essiac” is Caisse spelled backward.) Despite a lack of systematic research or documentation of its value, Essiac is promoted and purchased for all forms of cancer.[135]

Diet and Nutrition

Macrobiotic Diet

Various dietary regimens have been promoted for both prevention and treatment of cancer. The macrobiotic diet was first described by George Ohsawa (1893–1966). He developed a diet consisting of 10 stages, with each stage more restrictive than the previous one. The final stage consisted of only rice and water. The American Medical Association and various governmental agencies have opposed the macrobiotic diet owing to its restrictive nature. In fact, a number of health problems and even deaths have been reported among persons who have followed the diet.[137]

The macrobiotic diet subsequently has been modified and is regaining popularity in the United States and generally consists of 50% to 60% whole grains, 20% to 25% vegetables, 5% to 10% beans and sea vegetables, and 5% soups. Some variations of the diet allow small amounts of fish. There may be alterations of the diet depending on the disease process.

The Kushi Institute in Massachusetts is a strong proponent of the macrobiotic diet. This institute teaches the macrobiotic diet and lifestyle. Specific foods for the individual cancer patient are recommended. Numerous testimonials supporting the effectiveness of the macrobiotic diet are provided, but no controlled studies have been performed to evaluate the Kushi Institute methods.

A number of nutritional deficiencies have been reported in association with the macrobiotic diet. Breast milk from mothers who follow the macrobiotic diet contains less vitamin B12, calcium, magnesium, and saturated fatty acids than in the milk of mothers following “regular” diets.[138] Infants of mothers on the macrobiotic diet were found to have retarded growth, fat and muscle wasting, and slowed psychomotor development. Bone mineral content was evaluated in a study of adolescents who had followed a macrobiotic diet and compared with that in control patients without dietary restrictions.[139]The bone mineral content was found to be significantly lower in both boys and girls who had followed the macrobiotic diet. The study investigators suggest that this decreased bone density may hold important implications for fracture risk in later life. Machiels and associates reported a rare case of nutritional rickets in a young child due to the macrobiotic diet.[140]

Megadose Vitamin C: A Closer Look

The use of vitamin C for the treatment of cancer has been publicized for many years. Many continue to claim efficacy without strong scientific data to back these claims. Linus Pauling, PhD, and EwanCameron, MD, claimed that high doses of vitamin C could significantly improve survival in cancer patients. The claim was based on the known antioxidant properties of vitamin C and some epidemiologic evidence that populations with high dietary intake of the vitamin have a decreased risk for development of some types of cancer. These scientists believed that much higher doses than the recommended daily intake of 60 mg/day of vitamin C were needed to prevent free radical damage within the body. Pauling and Cameron reported a study of 100 patients in the terminal stages of cancer treated with megadose vitamin C who had significantly improved survival when compared with historical controls.[141] It was recommended that patients with cancer take 10,000 mg of vitamin C daily on the basis of their research.

The study was plagued by significant design issues. The “terminal” patients in the vitamin C treatment group all came from Dr. Cameron's practice, whereas the historical controls were “terminal” patients who came from other sources in the geograhic region. It is conceivable that significant selection bias occurred between Dr. Cameron's patients given vitamin C and the patients of other physicians who were not offered any additional treatments.

Owing to the exceptional reputation of Nobel Laureate Dr. Pauling, investigators at the Mayo Clinic performed a prospective randomized study to evaluate vitamin C. Creagan and colleagues randomized 150 patients with advanced cancer to receive 10 g of vitamin C or a placebo.[142] No difference in symptoms, performance status, appetite or survival was found between the two groups. These investigators concluded that high-dose vitamin C had no therapeutic benefit.

Dr. Pauling criticized the design of the Mayo Clinic study, claiming the patients had poor performance status and too much prior treatment with chemotherapy. Based on his criticisms, a new trial was launched. Moertel and coworkers randomized 100 patients with advanced colorectal cancer in a double-blind study to receive high-dose vitamin C (10 g daily) or a placebo.[143] No patient received previous cytotoxic therapy, and all had good performance status. Again, vitamin C showed no advantage over placebo therapy with regard to disease progression, objective improvement in measurable disease, or survival. The researchers concluded that high-dose vitamin C therapy is not effective against malignant disease regardless of whether the patient has had any prior chemotherapy.

In a recent trial of oral supplementation with ascorbic acid (vitamin C, 6100 mg/d), DL-alpha-tocopherol (a form of vitamin E, 1050 mg/d), and beta-carotene (vitamin A precursor, 60 mg/d), patients who had stage IIIB or IV non-small-cell lung cancer were randomly assigned to chemotherapy with paclitaxel and carboplatin (72 patients) or to this chemotherapy regimen plus the supplements (64 patients). No significant survival differences were reported, with 1-year survival rates of 33% and 39% and 2-year survival rates of 11% and 16% in the chemotherapy and the combination treatment groups, respectively.[144]

The argument has been made that the inability to confirm Pauling's results may reflect the use of oral rather than intravenous vitamin C. [9] [145] A 1.25-g dose of vitamin C given orally results in a mean plasma level of 135 μmol/L, whereas the same dose given intravenously results in a level of 885 μmol/L. The same study showed that the maximum tolerated oral dose of 3 g every 4 hours increased the plasma level to only 220 μmol/L, whereas the maximum tolerated intravenous dose of 50 g resulted in a plasma level of 13,000 μmol/L. The form of oral vitamin C also affects its bioavailability. A solution of vitamin C has an approximately 40% lower bioavailability than that of a slow-release formula.[146] Vitamin C intake also has been examined for the amelioration of toxicity associated with chemotherapy administration.

Weijl and colleagues[147] investigated the use of oral vitamin C, vitamin E, and selenium for the prevention of cisplatin-induced renal toxicity and ototoxicity. No significant overall effect was demonstrated, but a correlation with plasma levels of the vitamins and lower toxicity was observed. These investigators, however, concluded that poor compliance or inadequate supplementation may have confounded the results. Song and coworkers[148] investigated the use of an intravenous administration of 10 g vitamin C twice with a 3-day interval and an oral intake of 4 g vitamin C daily for a week. They then evaluated demographic data and assessed changes in patients’ reported quality of life after the administration of vitamin C. Quality of life was assessed with the EORTC QLQ-C30 questionnaire. These researchers concluded that high-dose vitamin C therapy did indeed significantly improve quality of life scores.

Side effects of megadose vitamin C include diarrhea, formation of renal stones, iron overload, and gastrointestinal discomfort. Ardent supporters of megadose vitamin C remain, however, despite the strong scientific evidence refuting its use in the treatment of cancer. Based on the current scientific literature, megadose vitamin C is not recommended for the prevention or treatment of cancer.


A multitude of potential interactions are possible between conventional cancer treatments and UMTs. Many such interactions are just beginning to be recognized by the medical establishment and reported in reputable scientific journals. [149] [150] Both renal and hepatic function can be impaired by various UMTs. [151] [152] [153] [154] [155] [156] Multiple biochemical pathways can be affected, including the lipoxygenase, cyclooxygenase, and cytochrome P-450 pathways.[112] Such effects may have an impact on drug concentrations in the body, resulting in increased toxicity or changes in effectiveness of chemotherapy and radiation therapy. Antioxidants may decrease the effectiveness of radiation therapy as a result of the scavenging of free radicals, which can damage DNA, leading to cell death.[157]Moreover, many of these therapies have their own side effects that can mimic those of conventional cancer treatments [158] [159] [160] [161] [162] [163] [164] [165] [166] [167] [168] [169] [170] [171] [172] [173] [174] [175] [176] [177] (Tables 35-2 and 35-3 [2] [3]). If the oncologist is not aware that a patient is using a particular UMT, signs or symptoms developing as a result of that UMT may be erroneously attributed to a conventional cancer treatment with established efficacy, which may then may be unnecessarily altered or discontinued.

Table 35-2   -- Potential Adverse Effects of Some Common Herbal and Other Alternative Medicines


Adverse Effect(s)

Ephedra species

Hypertension, tachycardia, stroke, seizures

St. John's wort

Depression, nausea, hypersensitivity reactions

Amygdalin (Laetrile)

Emesis, headache, dizziness, obtundation, dermatitis


Somnolence, confusion


Sedative, diarrhea, headache, hypertension, insomnia, nausea


Hypersensitivity reactions



Saw palmetto

Urinary retention, headache, diarrhea, constipation, hypertension, nausea


Local irritation, allergic reactions

Shark cartilage

Hepatitis, emesis, constipation


Emesis, headache

Green tea

Insomnia, emesis, diarrhea, confusion

Hydrazine sulfate

Hepatorenal failure

Goldenseal (Hydrastis canadensis)

Uterine contractions

Data from references 163 to 179 [163] [164] [165] [166] [167] [168] [169] [170] [171] [172] [173] [174] [175] [176] [177] [178] [179].



Table 35-3   -- Potential Interactions between Herbal Medicines and Conventional Drugs



Potential Interaction/Effect(s)

St. John's wort

Irinotecan, protease inhibitors, other drugs metabolized by cytochrome P-450

Reduced drug levels





Oral contraceptives





Hawthorn flower, devil's claw, licorice


Alters pharmacodynamics; drug levelmonitoring is prudent


Potassium-sparing diuretics

Affects potassium levels



Iodine content of herb may interfere with thyroid replacement



Additive sedative effects, coma




Evening primrose oil


Lowered seizure threshold

Feverfew, garlic, ginseng, gingko, ginger, dong quai


Altered bleeding time

Yohimbe bark

Centrally active antihypertensive agents

Yohimbine may antagonize guanabenz and methyldopa through its α2-adrenoceptor–antagonistic properties


Phenelzine sulfate

Headache, tremulousness, manic episodes


Estrogens, corticosteroids

Additive effects

Data from references 163 to 176 [163] [164] [165] [166] [167] [168] [169] [170] [171] [172] [173] [174] [175] [176].



Many forms of CAM are associated with no or minimal risk to a cancer patient; however, this is not true for all such therapies. It is well established that a variety of herbal medications may produce serious side effects. Quality control of these preparations can be a major concern. Issues include variability in biologic potency in different crops, the very realistic possibility of contamination (e.g., by fungal or bacterial organisms), and use of wrong plant species.[158] Herbal remedies may contain lead, arsenic, mercury, tin, or zinc, each of which can itself be toxic.[159]

Immunoaugmentative therapy (IAT) of Burton is based on balancing four protein components in the blood while strengthening the patient's immune system. The use of various organ extracts from cows and pigs is claimed to selectively suppress tumors and stimulate the immune defense cells. [160] [161] No studies have shown clinical effectiveness of immunoaugmentative therapy; however, samples of infected material from patients who received IAT revealed evidence of hepatitis virus.[161]

New toxic effects of a variety of herbal preparations continue to be reported. Kava, for example, a widely publicized natural sleep medication, has been associated with severe liver dysfunction, leading to at least one case of hepatic failure and the requirement for a liver transplant.[167] Other herbal medications also have been shown to be associated with hepatotoxicity.[168]

Laetrile (amygdalin), derived from apricot and other fruit pits, one of the oldest CAM medications, continues to be marketed to the public.[178] Amygdalin had been used for centuries, but, in the 1950s it was elevated to new heights under the trade name Laetrile. Proponents of Laetrile claim that proper use of this substance can eradicate cancer entirely (www.worldwithoutcancer.com andwww.sumeria.net/health/laetrile.html). Moertel and colleagues carried out a phase II clinical trial of Laetrile, along with vitamins A, C, E, and B complex and various minerals and pancreatic enzymes, in 178 patients with cancer not previously subjected to conventional cancer treatment and with good performance status. Only one patient, who had gastric carcinoma with cervical lymph node metastases, had a possible short-lived partial 10-week response. All others showed no signs of response. No evidence of disease stabilization was noted. Evaluation of toxicity revealed blood cyanide levels in the ranges known to kill animals and humans in several patients.[171] Studies have demonstrated that this drug can produce signs and symptoms of nausea, vomiting, headache, dizziness, and obtundation. [170] [171]

To date, one of the gravest examples of the potential for harm associated with herbal medications is that of the development of renal failure and urothelial carcinoma in persons who used the Chinese herbAristolochia fangchi. [179] [180] As a result of a manufacturing error, this herb replaced another preparation (Stephania tetrandra) used in a weight-reducing pill. More than 40 people who took this pill experienced progressive renal failure, and almost 50% subsequently were found to have a urothelial cancer.[179]

Vitamin toxicities are uncommon but well defined. Megadoses of vitamin A can cause increased intracranial pressure and vomiting in children, and its chronic use in adults can lead to hypercalcemia.[181]Vitamin B complex overdose can lead to cardiovascular toxicity including arrhythmias, edema, vasodilation, and allergic reactions. Megadoses of niacin can cause cardiac toxicity with arrhythmia, as well as liver toxicity and peptic ulceration. Long-term high-dose toxicities include gouty arthritis, hyperglycemia, dry skin, and rashes. Vitamin B6 in megadoses can cause peripheral neuropathies, with resulting numbness lasting for weeks. Vitamin C toxicities include the formation of renal stones.[182] High-dose vitamin E therapy can interfere with blood coagulation by antagonizing vitamin K and inhibiting prothrombin production. A recent study of vitamin E demonstrated an increased number of strokes in the vitamin E treatment group as compared with the control group.[183]

Both acupuncture and chiropractic medicine generally are quite safe; however, they too can be associated with irritating and more serious side effects. [184] [185] Reported toxic effects of acupuncture include transmission of infectious agents through needle insertion; broken, forgotten, or misapplied needles; pneumothorax; transient hypotension; minor bleeding; contact dermatitis; and pain.[184] A small but finite risk of a cerebrovascular accident is always associated with cervical spinal manipulations.[185]


The Internet has become a hotbed of CAM offerings and information over the past decade. However, patients must be advised to be extremely careful about where the information is being derived and what is being marketed over the Internet. Since the public introduction of the Internet in 1994, this computer resource has experienced exponential growth. In August 2002 it was estimated 64% of the U.S. population (177.6 million people) had access to the Internet.[186] This was increased from 56.5% of the population in October 2000.

Studies have been performed to specifically evaluate the use of the Internet by patients with cancer to obtain information about CAM. In a study of 921 patients presenting to radiation oncology centers in the United States, it was found 42% of those presenting to an academic medical center and 25% of those presenting to a community medical center were using the Internet to find cancer-specific information.[156] A questionnaire study from England showed that 24% of prostate cancer patients were using the Internet to obtain further health information.[187] A Canadian questionnaire study of patients with prostate cancer revealed that 35% of patients had used the Internet to obtain cancer-related information.[188] Another recent Canadian questionnaire study evaluated 191 cancer patients on the reliance on the news media and the Internet as sources of medical information.[189] This study showed that 50% used the Internet to obtain information and 7% used the Internet as their primary source of information. A study reporting on use of the Internet by 295 patients with prostate cancer in the United States showed that 32% were using the Internet to gather information.[190] Of interest, 58% of these patients used the Internet to search for information on CAM.

Many more patients probably are obtaining Internet-derived information from other people. As indicated by questionnaires placed on OncoLink (http://www.oncolink.upenn.edu), the cancer information resource from the University of Pennsylvania, many patients’ friends and family members are using the Internet to obtain cancer-related information. Vordermark and colleagues used a questionnaire study to identify where patients were obtaining information.[191] Of 139 German radiation oncology patients, 12% had used the Internet to obtain information about their cancer, but an additional 15% received Internet-derived information about their cancer from friends or family members. Of note, only 24% discussed the information obtained from the Internet with their physicians.

Yakren and coworkers used a patient survey to analyze the use of media information, including that from the Internet, among cancer patients and their companions at Memorial Sloan-Kettering Cancer Center.[192] As indicated by the responses of the 443 patients who returned the completed surveys, 44% of the patients and 60% of the companions reported use of the Internet to obtain cancer-related information. This is very similar to the utilization rate of 41% for patients at the University of Pennsylvania Cancer Center.[11]

The identification of good Internet sites can be difficult for the nonmedical person searching for information on complementary and alternative medicine. The general public requested 30% of all PubMed searches performed in 1999. A study by Bernstam and associates evaluated the ability of a computer-literate lay user to perform multiple searches for various question types related to cancer on MEDLINE.[193] A blinded investigator then rated each search's relevancy. The computer user was then given a custom interface to help with the searches through MEDLINE. Overall, significantly higher precision was observed with use of the MEDLINE interface than with unaided novice searching. This finding emphasizes the need for the medical community to help guide patients’ search for medically relevant information on the Internet. Although this study does not specifically evaluate Web searches, these results may be generalizable to patients looking for information on the Internet regarding CAM.

It can be a daunting task for the nonmedical person to objectively evaluate the quality of Internet sites, particularly those offering CAM. A recent study by RAND Health reported on the quality of health information on the Internet.[194] A variety of health Web sites were evaluated, including 20 major Web sites for breast cancer information. It was found that on average, two to four websites needed to be visited to find more than minimal coverage for at least 75% of the indicators for a topic. Although experts may be able to quickly evaluate the quality and appropriate coverage of a topic, as in the RAND study, this can be very difficult for the patient. Meric and colleagues found that popularity and traffic of breast cancer Websites do not always correlate with quality.[195] This finding again emphasizes the need for professionals to help guide the lay public to appropriate medical material on the Internet.

Most health care providers have experienced a visit from a patient entering the office with pages of CAM information printed from the Internet. Only a limited number of studies, however, have documented the use of the Internet to find information on CAM. A study from the University of Pennsylvania showed that 53% of cancer patients using the Internet were interested in finding information about CAM.[196] Most of these patients were doing so without their health care providers’ knowledge. CAM therapies were purchased over the Internet by 12% of Internet users in this study. However, this study did not specifically evaluate the type of therapy purchased. Health care providers need to familiarize themselves with the therapies offered over the Internet in order to have an informed discussion with their patients regarding these treatments. Particular discussions should emphasize the potential side effects and interactions with conventional cancer treatments.[11] A typical search on Yahoo, one of the Internet search engines (http://www.yahoo.com), for “alternative and complementary medicine” reveals greater than 6.14 million different Web site matches. This is increased from 432,000 in 2004. Some of these Web sites provide credible information. Unfortunately, many are designed only to sell a specific product and give false or misleading information. It can be overwhelming for the average person without medical knowledge to sift through and understand the claims presented on many of these sites.

Some patients will ask their health care providers for recommendations on evaluating Web sites offering CAM information. It generally is recommended to start with sites managed by major academic centers and the government. These institutions maintain a level of quality outside of the Internet that typically is upheld on these Web sites in keeping with the general philosophies of these organizations. Patients also should be warned to be wary of sites designed to sell a specific product or treatment. Many of these sites do not give unbiased information and are designed strictly to generate revenue. Box 35-4 provides some suggestions to guide patients in evaluating Internet sites. Table 35-4 recommends selected Web sites with reliable information on CAM for the cancer patient and health care provider.

Box 35-4 




Accuracy of information: Websites that post information that is not referenced, or articles that do not state authors and dates for content, should be avoided.



Availability of editorial staff: An online resource should list the names of its editorial staff, the credentials of the people behind the resource. An address and email contact information also should be provided.



Qualifications of editorial staff: Many online resources are run by people who are not qualified to provide medical advice. Fundamentally, there is nothing wrong with this, provided that it is clearly stated. In general, however, the best information is provided by health care professionals who are health care providers themselves. Much of what physicians, nurses, and other professionals are trained to do involves interacting with patients and providing information in the clearest, most appropriate manner.



Freshness of content: Sites with content that is updated regularly are likely to be ones that are best managed and most up to date.



Disclosure of conflicts of interest: Conflicts of interest should either be obvious or clearly disclosed to the users.



Price of information: So far, very few online medical resources are charging for information. Although this may change in the future, open access to information with fees that are minimal should be the rule. If you are being charged for the information, make sure it is not information others are providing for free.



Confidentiality: Most online medical resources will not respond to direct medical inquiries by users. This is due in part to concerns about patient confidentiality, and about accuracy of information either sent to or received by the patient. It is important to ensure that sites that require registration are not releasing contact data without permission.



Reputation: Resources known to be run by reputable institutions are more likely to be providing more timely, accurate, and unbiased information.



Look and “feel”: Resources must balance between having an attractive resource and being able to provide the best possible information to users. Certainly, content rich in graphics is attractive, but if it is poorly organized, or if downloading it takes an inordinate amount of time, it may not be serving its primary purpose.



Navigation and searching: Make sure a site is well organized and easy to navigate and has a good search engine.

Reproduced, with slight modifications, with permission from the editors at http://www.oncolink.org.

Table 35-4   -- Selected Web Sites with Reliable Information on Complementary and Alternative Medicine


Web Address

American Botanical Council


American Cancer Society


M.D. Anderson Cancer Center


Memorial Sloan-Kettering Cancer Center


National Cancer Institute


National Center for Complementary and Alternative Medicine


Office of Complementary and Alternative Medicine


OncoLink (University of Pennsylvania Cancer Center)






Numerous cancer clinics promoting alternative medicine techniques have formed throughout the world. Many centers are transient, but some have been established for quite some time and have a large following and have marketed their facilities to the general public. A complete enumeration is beyond the scope of this chapter, but none of the treatments offered by these facilities are known to have shown verifiable beneficial results when compared with conventional medical treatments. Nevertheless, case reports and testimonials abound. It is important that health care providers recognize that these treatments are being promoted to their patients through the Internet and print publications, and by word of mouth.

For example, Tijuana, Mexico, has long been a destination for patients seeking alternative medical therapies. The government has acted to close down a number of these centers at various times, but many continue to thrive. At any one time, some 50 to 70 alternative medicine clinics are in operation. It has been estimated that roughly 40,000 people travel to Tijuana in search of alternative treatments each year. Of these patients, 95% are from the United States. Many of these clinics operate in a hospital-type atmosphere, and patients stay for a number of days or weeks for their therapy. A few such clinics are strictly outpatient or day treatment centers.

The therapies offered in these centers range from simple dietary management to complex operative treatments. Some of these treatments are innocuous, whereas others may be quite dangerous. For instance, some patients are offered insulin-induced hypoglycemia therapy (IHT). Patients are given insulin to drop the blood glucose level to less than 40 mg/dL and then are infused with a glucose solution incorporating a diluted chemotherapy preparation. The rationale for this treatment is that “starving” cancer cells need more glucose and thus more readily take up the chemotherapy drugs, so no side effects develop.

Claims of benefit by these alternative medicine centers have not been substantiated by the outside medical establishment. As confirmed by our own observations in such centers, however, some patients with hormone-responsive tumors such as breast cancer and prostate cancer are receiving hormonal therapies. Also, as mentioned earlier, chemotherapy sometimes is offered along with the alternative treatments. This may account for some for the claims of response to these treatments.

These treatments generally constitute out-of-pocket medical expenditures, because these are not covered by medical insurance programs. Table 35-5 shows the estimated cost at some of the more popular centers offering alternative cancer treatments. Some of the prices do not include room and board. Many have added charges that may not become specified until the patient is seen and evaluated at the clinic. All require cash payment before treatment. Travel expenses are not included in the estimates.

Table 35-5   -- Popular Unconventional Cancer Therapy Clinics



Type of Treatment

Duration of Therapy

Estimated Cost

Kushi Institute

Brookline, Massachusetts

Macrobiotic diet

1 week


Burzynski Clinic

Houston, Texas


6 months


Immuno-Augmentive Centre



3 months


Hosp de Baja California del Sol


Gerson Method

1 month


Bio Medical Center


Hoxsey Herbal



Center for Cell Specific Therapy

Santo Domingo

Magnet Therapy




Based on published advertising on the Internet of $1,495 for 1 week. Private counseling sessions are an additional $225 each.

Based on telephone quotation of intravenous therapy of $14,000 for the first month and $7,200 for each additional month, which averages 6 months in duration. Cost of the oral formula is $6,000 for the first month and $2,000 for each additional month.

Published advertising fee schedule from the Immuno-Augmentive Centre of $7,500 for the first 4 weeks and $700 per week thereafter, up to 8 additional weeks. Cost of supplies for home maintenance is $50 per week indefinitely.


Based on published advertising on the Internet of $3,990 per week for basic charges, with a recommended stay of 1 month; “…actual costs for any individual will become evident only during the course of treatment.”

Based on telephone quotation of $3,500 lifetime supply of Hoxsey Tonic, $300 to $400 for blood work, and $25 consultation fee.

Based on brochure from the Center for Cell Specific Therapy. All patients are charged $20,000 regardless of the length of treatment.



Many patients with cancer, as well as their friends and and family members, are searching for information regarding CAM. Health care providers must become educated on this topic so that they can appropriately guide these patients. CAM is here to stay, and patients need to be supported in their decision to use complementary therapies that are safe. Health care providers must warn patients of potential or known interactions with conventional medications and treatments when appropriate. Clinical trials evaluating CAM should be developed and encouraged. CAM needs to be held to the same stringent criteria as those in place for conventional treatment modalities.


  1. National Institutes of Health : Alternative Medicine: Expanding Medical Horizons,  Washington, DC, U.S. Government Printing Office, 1992.
  2. Cassileth BR: “Complementary” or “alternative”? It makes a difference in cancer care.  Complement Ther Med1999; 7:35.
  3. Schimpff SC: Complementary medicine.  Curr Opin Oncol1997; 9:327.
  4. Panel on Definition and Description : Defining and describing complementary and alternative medicine. CAM Research Methodology Conference, April 1995.  Altern Ther1997; 3:49.
  5. Risberg T, Lund E, Wist E, et al: Cancer patients' use of nonproven therapy: a 5-year follow up study.  J Clin Oncol1999; 16:6-12.
  6. Liu JM, Chu HC, Chin YH, et al: Cross sectional study of use of alternative medicine in Chinese cancer patients.  Jpn J Clin Oncol1997; 27:37-41.
  7. Begbie SD, Kerestes ZL, Bell DR: Patterns of alternative medicine use by cancer patients.  Med J Aust1996; 165:545-548.
  8. Downer SM, Cody MM, McCluskey P, et al: Pursuit and practice of complementary therapies by cancer patients receiving conventional treatment.  BMJ1994; 309:86-89.
  9. Lerner IJ, Kennedy BJ: The prevalence of questionable methods of cancer treatment in the United States.  CA Cancer J Clin1992; 42:181-191.
  10. Burstein HJ, Gelber S, Guadagnoli E, et al: The use of complementary health strategies by women with early stage breast cancer.  Proc Am Soc Clin Oncol1998;17.
  11. Metz JM, Jones H, Devine P, et al: Cancer patients use unconventional medical therapies far more frequently than standard history and physical examination suggest.  Can J Sci Am2001; 7:149-154.
  12. Grootenhuis MA, Last BF, de Graff-Nijkerk JH, et al: Use of alternative treatment in pediatric oncology.  Cancer Nurs1998; 21:282-288.
  13. Fernandez CV, Stutzer CA, MacWilliam L, et al: Alternative and complementary therapy use in pediatric oncology patients in British Columbia: prevalence and reasons for use and nonuse.  J Clin Oncol1998; 16:1279-1286.
  14. Blendon RJ, DesRoches CM, Benson JM, et al: Americans' views on the use and regulation of dietary supplements.  Arch Intern Med2001; 161:805-810.
  15. Conner M, Kirk SF, Cade JE, Barrett JH: Why do women use dietary supplements? The use of the theory of planned behaviour to explore beliefs about their use.  Soc Sci Med2001; 52:621-633.
  16. Frank E, Bendich A, Denniston M: Use of vitamin-mineral supplements by female physicians in the United States.  Am J Clin Nutr2000; 72:969-975.
  17. Neuhouser ML, Patterson RE, Levy L: Motivations for using vitamin and mineral supplements.  J Am Diet Assoc1999; 99:851-854.
  18. Patterson RE, Neuhouser ML, White E, et al: Cancer-related behavior of vitamin supplement users.  Cancer Epidemiol Biomarkers Prev1998; 7:79-81.
  19. World Cancer Research Fund and the American Institute for Cancer Research : Food, nutrition and the prevention of cancer: a global perspective,  Washington, DC, American Institute for Cancer Research, 1997.
  20. Knekt P, Aromaa A, Maatela J, et al: Vitamin E and cancer prevention.  Am J Clin Nutr (Suppl)1991; 53:283S-286S.
  21. Block G: Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence.  Nutr Cancer1992; 18:1-29.
  22. Stahelin H, Gey K, Eichholzer M: Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel study.  Am J Epidemiol1991; 133:766-775.
  23. Nomura AM, Stemmermann G, Heilbrun L: Serum vitamin levels and the risk of cancer of specific sites in men of Japanese ancestry in Hawaii.  Cancer Res1985; 45:2369-2372.
  24. Hennekens CH, Stampfer MJ, Willett W: Micronutrients and cancer chemoprevention.  Cancer Detect Prev1984; 7:147-158.
  25. Woutersen RA, Appel MJ, Van Garderen-Hoetmer A: Modulation of pancreatic carcinogenesis by antioxidants.  Food Chem Toxicol1999; 37:981-984.
  26. Nomura AM, Stemmermann G, Heilbrun L: Serum vitamin levels and the risk of cancer of specific sites in men of Japanese ancestry in Hawaii.  Cancer Res1985; 45:2369-2372.
  27. Hong WK, Lippman SM, Itri L: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck.  N Engl J Med1990; 323:795-801.
  28. Moore SR, Hill KA, Heinmoller PW, et al: Spontaneous mutation frequency and pattern in Big Blue mice fed a vitamin E–supplemented diet.  Environ Mol Mutagen1999; 34:195-200.
  29. Lippman SM, Lee JJ, Sabichi AI: Cancer chemoprevention: progress and promise.  J Natl Cancer Inst1998; 90:1514-1528.
  30. Alpha Tocopherol Beta Carotene Trial Group : The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers.  N Engl J Med1994; 330:1029-1035.
  31. Omenn GS, Goodman GE, Thornquist M, et al: The Beta-Carotene and Retinol Efficacy Trial (CARET) for chemoprevention of lung cancer in high-risk populations: smokers and asbestos-exposed workers.  Cancer Res1994; 54:203S-243S.
  32. Li JY, Taylor PR, Dawsey S, et al: Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophagel dysplasia.  J Natl Cancer Inst1994; 86:1645-1649.
  33. Crawford ED, Fair WR, Kelloff GJ, et al: Chemoprevention of prostate cancer: guidelines for possible intervention strategies!.  J Cell Biochem Suppl1992; 16H:140-145.
  34. Blutt SE, Weigel NL: Vitamin D and prostate cancer.  Proc Soc Exp Biol Med1999; 221:89-98.
  35. Hyman J, Baron JA, Dain BJ, et al: Dietary and supplemental calcium and the recurrence of colorectal adenomas.  Cancer Epidemiol Biomarkers Prev1998; 7:291-295.
  36. Clark LC, Combs GF, Turnbull BW, et al: Effect of selenium supplementation for cancer prevention with carcinoma of the skin: a randomized controlled trial.  JAMA1996; 276:1957-1963.
  37. Setchell KDR, Cassidy A: Dietary isoflavones: biological effects and relevance to human health.  J Nutr1999; 129:758S-767S.
  38. Messina MJ, Persky V, Setchell KDR: Soy intake and cancer risk: review of the in vivo and in vitro data.  Nutr Cancer1994; 21:113-131.
  39. Messina MJ, Barnes S: The role of soy products in reducing risk of cancer.  J Natl Cancer Inst1991; 83:541-546.
  40. Kennedy AR: The evidence for soybean products as cancer preventive agents.  J Nutr1995; 125:733S-743S.
  41. Complementary and alternative medicine [entire issue].  JAMA1998; 280:1549-1640.
  42. Ernst E, Pittler MH: Herbal medicine.  Med Clin North Am2002; 86:
  43. Eisenberg DM, Davis RB, Ettner SL, et al: Trends in alternative medicine use in the United States, 1990–1997.  JAMA1998; 280:1569-1575.
  44. Eisenberg DM, Kessler RC, Foster C, et al: Unconventional medicine in the United States: prevalence, costs, and patterns of use.  N Engl J Med1993; 328:246-252.
  45. Brevoort P: The booming US botanical market: a new overview.  HerbalGram1998; 44:33-48.
  46. Jones HA, Metz JM, Devine P, et al: Rates of unconventional medical therapy use in patients with prostate cancer: standard history versus directed questions.  Urology2002; 59:272-276.
  47. Spence Cohen MJ: Complementary and alternative medicine: legal boundaries and regulatory perspectives,  Baltimore, Johns Hopkins University, 1998.
  48. Ang-Lee MK, Moss J, Yuan CS: Herbal medicines and perioperative care.  JAMA2001; 286:208-216.
  49. De Smet PA: Herbal remedies.  N Engl J Med2002; 347:2046-2056.
  50. In: Blumenthal M, ed. The Complete German Commission E Monographs Therapeutic Guide to Herbal Medicines,  Austin, Tex.: American Botanical Council; 1998.
  51. Licensing of medicines: policy on herbal medicines. Herbal safety news. London, Medicines Control Agency, 2002. Accessed November 22, 2002, athttp://www.mca.gov.uk/ourwork/licensingmeds/herbalmeds/herbalsafety.htm
  52. Bing Z, Villanueva L, LeBars D: Acupuncture-evoked responses of subnucleus reticularis dorsalis neurons in the rat medulla.  Neuroscience1991; 44:693-703.
  53. Grossman A, Clement-Jones V: Opiate receptors: enkephalins and endorphins.  Clin Endocrinol Metab1983; 12:31-56.
  54. Matsumoto T, Lyu BS: Anatomical comparison between acupuncture and nerve block.  Am Surg1975; 41:11-16.
  55. NIH Consensus Development Panel on Acupuncture : Acupuncture.  JAMA1998; 280:1518-1524.
  56. Filshie J, Thompson JW: Acupuncture.   In: Doyle D, Hanks G, Cherny N, et al ed. Oxford Textbook of Palliative Medicine,  3rd ed.. Oxford, UK: Oxford University Press; 2004:410-424.
  57. Filshie J: Safety aspects of acupuncture in palliative care.  Acupunct Med2001; 19:117-122.
  58. Dundee JW, Yang J: Prolongation of the antiemetic action of P6 acupuncture by acupressure in patients having cancer chemotherapy.  J R Soc Med1990; 83:360-362.
  59. Kotani N, Hashimoto H, Sato Y, et al: Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses.  Anesthesiology2001; 95:349-356.
  60. He JP, Friedrich M, Ertan AK, et al: Pain-relief and movement improvement by acupuncture after ablation and axillary lymphadenectomy in patients with mammary cancer.  Clin Exp Obstet Gynecol1999; 26:81-84.
  61. Lee H, Schmidt K, Ernst E: Acupuncture for the relief of cancer-related pain—a systematic review.  Eur J Pain2005; 9:437-444.
  62. Alimi D, Rubino C, Pichard-Leandri E, et al: Analgesic effect of auricular acupuncture for cancer pain: a randomized, blinded, controlled trial.  J Clin Oncol2003; 21:4120-4126.
  63. Wen HL: Cancer pain treated with acupuncture and electrical stimulation.  Mod Med Asia1977; 13:12-16.
  64. Filshie J, Redman D: Acupuncture and malignant pain problems.  Eur J Surg Oncol1985; 11:389-394.
  65. Filshie J: Acupuncture for malignant pain.  Acupunct Med1990; 8:38-39.
  66. Aung S: The clinical use of acupuncture in oncology: symptom control.  Acupunct Med1994; 12:37-40.
  67. Filshie J, Scase A, Ashley S, et al: A study of the acupuncture effects on pain, anxiety and depression in patients with breast cancer. Presented at the Pain Society Meeting. Newcastle, UK, April 1997.
  68. Dillon M, Lucas CF: Auricular stud acupuncture in palliative care patients: an initial report.  Palliat Med1999; 13:253-254.
  69. Leng G: A year of acupuncture in palliative care.  Palliat Med1999; 13:163-164.
  70. Johnstone PA, Polston GR, Niemtzow RC, Martin PJ: Integration of acupuncture into the oncology clinic.  Palliat Med2002; 16:235-239.
  71. Ezzo J, Vickers A, Richardson MA, et al: Acupuncture-point stimulation for chemotherapy induced nausea and vomiting.  J Clin Oncol2005; 23:7188-7198.
  72. Shen J, Wenger N, Glaspy J, et al: Electroacupuncture for control of myeloablative chemotherapy-induced emesis: a randomized controlled trial.  JAMA2000; 284:2755-2761.
  73. Ahlberg K, Ekman T, Gaston-Johansson F, et al: Assessment and management of cancer-related fatigue in adults.  Lancet2003; 362:640-650.
  74. Stasi R, Abriani L, Beccaglia P, et al: Cancer-related fatigue: evolving concepts in evaluation and treatment.  Cancer2003; 98:1786-1801.
  75. Vickers AJ, Straus DJ, Fearon B, et al: Acupuncture for postchemotherapy fatigue: a phase II study.  J Clin Oncol2004; 22:1731-1735.
  76. Johnstone PA, Peng YP, May BC, et al: Acupuncture for pilocarpine-resistant xerostomia following radiotherapy for head and neck malignancies.  Int J Radiat Oncol Biol Phys2001; 50:353-357.
  77. de Valois B, Jackson L: Using traditional acupuncture for hot flushes and night sweats in women taking Tamoxifen—a pilot study.  British Acupuncture Council2003; 8:25.
  78. Cumins SM, Brunt AM: Does acupuncture influence the vasomotor symptoms experienced by breast cancer patients taking tamoxifen?.  Acupunct Med2000; 18:28.
  79. Woodson CM, Shalts E: Homeopathy.  Med Clin North Am2002;86.
  80. Eskinazi D: Homeopathy re-revisited.  Arch Intern Med1999; 159:1981-1987.
  81. Helyer L, Chin S, Chui BK, et al: The use of complementary and alternative medicines among patients with locally advanced breast cancer—a descriptive study.  BMC Cancer2006; 6:39.
  82. Ernst E: A systematic review of systematic reviews of homeopathy.  Br J Clin Pharmacol2002; 54:577-582.
  83. Jonas WB, Kaptchuk TJ, Linde K: A critical overview of homeopathy.  Ann Intern Med2003; 138:393-399.
  84. Shang A, Huwiler-Muntener K, Nartey L, et al: Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.  Lancet2005; 366:726-732.
  85. Linde K, Clausius N, Ramirez G, et al: Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials.  Lancet1997; 350:834-843.
  86. Linde K, Melchart D: Randomized controlled trials of individualized homeopathy: a state-of-the-art review.  J Altern Complement Med1998; 4:371-388.
  87. Ironson G, Field T, Scafidi F, et al: Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.  Int J Neurosci1996; 84:205-217.
  88. Field T: Massage therapy.  Med Clin North Am2002;86.
  89. In: Shealy CN, Thomas R, ed. The Complete Family Guide to Alternative Medicine,  Rockport, Mass.: Element Books; 1996.
  90. Carey TS, Garrett J, Jackman A, et al: The outcomes and costs of care for acute low back pain among patients seen by primary care practitioners, chiropractors and orthopedic surgeons: the North Carolina back pain project.  N Engl J Med1995; 333:913-917.
  91. Cherkin DC, Deyo RA, Battie M, et al: A comparison of physical therapy, chiropractic manipulation and provision of an educational booklet for the treatment of patients with low back pain.  N Engl J Med1998; 339:1021-1029.
  92. Cherkin D, Mootz R: Chiropractic in the United States: training, practice and research. AHCPR Publication No. 98–N002, 1997.
  93. Chopra A, Doiphode VV: Ayurvedic medicine: core concept, therapeutic principles, and current relevance.  Med Clin North Am2002; 86(1):
  94. Upadhyay RL: Prevention of diseases: an Ayurvedic approach.  Indian J Med Sci1998; 52:119-124.
  95. Burish TG, Jenkins RA: Effectiveness of biofeedback and relaxation training in reducing the side effects of cancer chemotherapy.  Health Psychol1992; 11:17-23.
  96. Syrjala KL, Donaldson , Davis MW, et al: Relaxation and imagery and cognitive-behavioral training reduce pain during cancer treatment: a controlled clinical trial.  Pain1995; 63:189-198.
  97. Darzynkiewicz Z, Traganos F, Wu JM, Chen S: Chinese herbal mixture PC SPES in treatment of prostate cancer [review].  Int J Oncol2000; 17:729-736.
  98. de la Taille A, Hayek OR, Buttyan R, et al: Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients.  BJU Int1999; 84:845-850.
  99. DiPaola RS, Zhang H, Lambert GH, et al: Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer [see comments].  N Engl J Med1998; 339:785-791.
  100. Pfeifer BL, Pirani JF, Hamann SR, Klippel KF: PC-SPES, a dietary supplement for the treatment of hormone-refractory prostate cancer.  BJU Int2000; 85:481-485.
  101. Small EJ, Frohlich MW, Bok R, et al: Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer.  J Clin Oncol2000; 18:3595-3603.
  102. Lock M, Loblaw DA, Choo R, et al: Disseminated intravascular coagulation and PC-SPES: a case report and literature review.  Can J Urol2001; 8:1326-1329.
  103. Schiff JD, Ziecheck WS, Choi B: Pulmonary embolus related to PC-SPES use in a patient with PSA recurrence after radical prostatectomy.  Urology2002; 59:444.
  104. Weinrobe MC, Montgomery B: Acquired bleeding diathesis in a patient taking PC-SPES.  N Engl J Med2001; 345:1213-1234.
  105. Cassileth BR, Vickers AJ: Urol Clin North Am2002;30.
  106. Gold J: Use of hydrazine sulfate in terminal and preterminal cancer patients: results of investigational new drug (IND) study in 84 evaluable patients.  Oncology1975; 32:1-10.
  107. Loprinzi CL, Goldberg RM, Su JQ, et al: Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer.  J Clin Oncol1994; 12:1126-1129.
  108. Loprinzi CL, Kuross SA, O'Fallon JR, et al: Randomized placebo controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer.  J Clin Oncol1994; 12:1121-1125.
  109. Kosty MP, Fleishman SB, Herndon JE, et al: Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B.  J Clin Oncol1994; 12:1113-1120.
  110. Wellings SR: Neoplasia and primitive vertebrate phylogeny: echinoderms, prevertebrates, and fishes—a review.  Natl Cancer Inst Monogr1969; 31:59-128.
  111. Prieur DJ, Fenstermacher JD, Guarino AM: A choroid plexus papilloma in an elasmobranch (Squalus acanthias).  J Natl Cancer Inst1976; 56:1207-1208.
  112. Wolke RE, Murchelano RA: A case report of an epidermal papilloma in Mustelus canis.  J Wildl Dis1976; 12:167-171.
  113. Langer R, Lee A: Shark cartilage contains inhibitors of tumor angiogenesis.  Science19893; 221:1185-1187.
  114. Mathews J: Media feeds frenzy over shark cartilage as cancer treatment.  J Natl Cancer Inst1993; 85:1190-1191.
  115. Miller DR, Granick JL, Stark JJ, et al: Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancers.  Proc Am Soc Clin Oncol1997; 16:
  116. Ashar B, Vargo E: Shark cartilage-induced hepatitis.  JAMA1996; 125:780-781.
  117. Grothey A, Duppe J, Hasenburg A, Voigtmann R: Use of alternative medicine in oncology patients.  Dtsch Med Wochenschr1998; 123:923-939.
  118. Munstedt K, Kirsch K, Milch W, et al: Unconventional cancer therapy: survey of patients with gynaecological malignancy.  Arch Gynecol Obstet1996; 258:81-88.
  119. Bocci V: Mistletoe (Viscum album) lectins as cytokine inducers and immunoadjuvant in tumor therapy: a review.  J Biol Regul Homeost Agents1993; 7:1-6.
  120. Mannel DN, Becker H, Gundt A, et al: Induction of tumor necrosis factor expression by a lectin from Viscum album.  Cancer Immunol Immunother1991; 33:177-182.
  121. Lenartz D, Stoffel B, Menzel J, Beuth J: Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients.  Anticancer Res1996; 16:3799-3802.
  122. Jung ML, Baudino S, Ribereau-Gayon G, Beck JP: Characterization of cytotoxic proteins from mistletoe (Viscum album L.).  Cancer Lett1990; 51:103-108.
  123. Kleijnen J, Knipschildm P: Mistletoe treatment for cancer: review of controlled trials in humans.  Phytomedicine1994; 1:255-260.
  124. Steuer-Vogt MK, Bonkowsky V, Ambrosch P, et al: The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.  Eur J Cancer2001; 37:23-31.
  125. Eggermont AM, Keilholz U, Autier P, et al: The EORTC Melanoma Group: a comprehenisve melanoma research programme for clinicians and scientists.  Eur J Cancer2002; 38(Suppl 4):S114-S119.
  126. Gillis CN: Panax ginseng pharmacology: a nitric oxide link?.  Biochem Pharmacol1997; 54:1-8.
  127. Elam JL, Carpenter JS, Shu XO, et al: Methodological issues in the investigation of ginseng as an intervention for fatigue.  Clin Nurse Spec2006; 20:183-189.
  128. Kim JH, Park CY, Lee SJ: Effects of sun ginseng on subjective quality of life in cancer patients: a double-blind, placebo-controlled pilot trial.  J Clin Pharm Ther2006; 31:331-334.
  129. Izzo AA, Ernst E: Interactions between herbal medicines and prescribed dugs: a systematic review.  Drugs2001; 61:2163.
  130. Borrelli F, Capasso R, Aviello G, et al: Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting.  Obstet Gynecol2005; 105:849-856.
  131. Bryer E: A literature review of the effectiveness of ginger in alleviating mild-to-moderate nausea and vomiting of pregnancy.  J Midwifery Womens Health2005; 50:1-3.
  132. Smith C, Crowther C, Willson K, et al: A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy.  Obstet Gynecol2004; 103:639-645.
  133. Vutyavanich T, Kraisarin T, Ruangsri R: Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial.  Obstet Gynecol2001; 97:577-582.
  134. Sripramote M, Lekhyananda N: A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy.  J Med Assoc Thai2003; 86:846-853.
  135. Manusirivithaya S, Sripramote M, Tangjitgamol S, et al: Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin.  Int J Gynecol Cancer2004; 14:1063-1069.
  136. Kaegi E: Unconventional therapies for cancer: 1. Essiac. The Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative.  Can Med Assoc J1998; 158:897-902.
  137. Metz JM: Alternative medicine and the cancer patient: an overview.  Med Pediatr Oncol2000; 34:20-26.
  138. Dagnelie PC, van Staveren WA: Macrobiotic nutrition and child health: results of a population-based, mixed-longitudinal cohort study in The Netherlands.  Am J Clin Nutr1994; 59:1187S-1196S.
  139. Parsons TJ, van Dusseldorp M, van der Vliet M, et al: Reduced bone mass in Dutch adolescents fed a macrobiotic diet early in life.  J Bone Miner Res1997; 12:1486-1494.
  140. Machiels F, De Maeseneer M, Van Snick A, et al: A rare cause of rickets in a young child.  J Belge Radiol1995; 78:276-277.
  141. Cameron E, Pauling L: Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer.  Proc Natl Acad Sci USA1976; 73:3685-3689.
  142. Creagan ET, Moertel CG, O'Fallen JR, et al: Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial.  N Engl J Med1979; 301:687-690.
  143. Moertel CG, Fleming TR, Creagan ET, et al: High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison.  N Engl J Med1985; 312:137-141.
  144. Pathak AK, Bhutani M, Guleria R, et al: Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer.  J Am Coll Nutr2005; 24:16-21.
  145. Padayatty SJ, Sun H, Wang Y, et al: Vitamin C pharmacokinetics: implications for oral and intravenous use.  Ann Intern Med2004; 140:533-537.
  146. Bhagavan HN, Wolkoff BI: Correlation between the disintegration time and the bioavailability of vitamin C tablets.  Pharm Res1993; 10:239-242.
  147. Weijl NI, Elsendoorn TJ, Lentjes EG, et al: Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatinbased chemotherapy: a randomised, double-blind, placebo-controlled study.  Eur J Cancer2004; 40:1713-1723.
  148. Yeom CH, Jung GC, Song KJ: Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration.  J Korean Med Sci2007; 22:7-11.
  149. Cupp MJ: Herbal remedies: adverse effects and drug interactions.  Am Fam Physician1999; 59:1239-1245.
  150. Cheng TO: Herbal interactions with cardiac drugs.  Arch Intern Med2000; 160:870-871.
  151. Harvey J, Colin-Jones DG: Mistletoe hepatitis.  Br Med J (Clin Res Ed)1981; 282:186-187.
  152. Gordon DW, Rosenthal G, Hart J, et al: Chapar-ral ingestion: the broadening spectrum of liver injury caused by herbal medications.  JAMA1995; 273:489-490.
  153. Ridker PM, Ohkuma S, McDermott WV, et al: Hepatic venocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements.  Gastroenterology1985; 88:1050-1054.
  154. Woolf GM, Petrovic LM, Rojter SE, et al: Acute hepatitis associated with the Chinese herbal product jin bu huan.  Ann Intern Med1994; 121:729-735.
  155. Larrey D, Vial T, Pauwels A, et al: Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity.  Ann Intern Med1992; 117:129-132.
  156. Nortier JL, Muniz Martinez MC, Schmeiser HH, et al: Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi).  N Engl J Med2000; 342:1686-1692.
  157. Salganik RI, Albright CD, Rodgers J, et al: Avoiding vitamins A and E may improve cancer therapy.  Proc Am Soc Cell Biol1999;
  158. Murch SJ, KrishnaRaj S, Saxena PK: Phytophar-maceuticals: problems, limitations, and solutions.  Scientif Rev Alternative Med2000; 4:33-37.
  159. Spencer D'Arcy PF: Adverse reaction and interactions with herbal medications.  Adverse Drug React Toxicol Rev1991; 10:189.
  160. Cassileth BR, Chapman CC: Alternative and complementary cancer therapies.  Cancer Invest1996; 14:396.
  161. Hauser SP: Unproven methods in cancer treatment.  Curr Opin Oncol1993; 5:646.
  162. U.S. Congress Office of Technology Assessment: Colin immunoaugmentative therapy: unconventional cancer treatment. Pub. No. OTH-H-405,  Washington, DC: U.S. Government Printing Office; 1990:129-14735.
  163. Markman M: Safety issues in using complementary and alternative medicine.  J Clin Oncol2002; 20(suppl):39S-41S.
  164. Ernst E: The risk-benefit profile of commonly used herbal therapies: ginkgo, St. John's wort, ginseng, Echinacea, saw palmetto, and kava.  Ann Intern Med2002; 136:42-53.
  165. Haller CA, Benowitz NL: Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids.  N Engl J Med2000; 343:1833-1838.
  166. Echinacea for prevention and treatment of upper respiratory infections.  Med Lett Drugs Ther2002; 44:29-32.
  167. Grossman L: The curious case of kava: why did it take the FDA so long to finally sound the alarm?.  TimeApril 8, 2002;58.
  168. MacGregor FB, Abernethy VE, Dahabra S, et al: Hepatotoxicity of herbal remedies.  BMJ1989; 299:1156-1157.
  169. Hainer MI, Tsai N, Komura ST, et al: Fatal hepatorenal failure associated with hydrazine sulfate.  Ann Intern Med2000; 133:877-880.
  170. Moertel CG, Ames MM, Kovach JS, et al: A pharmacologic and toxicological study of amygdalin.  JAMA1981; 245:591-594.
  171. Moertel CG, Fleming TR, Rubin J, et al: A clinical trial of amygdalin (Laetrile) in the treatment of human cancer.  N Engl J Med1982; 306:201-206.
  172. Miller DR, Anderson GT, Stark JJ, et al: Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer.  J Clin Oncol1998; 16:3649-3655.
  173. Parker MG: Shark cartilage–induced hepatitis.  Ann Intern Med1996; 125:780-781.
  174. Buckner JC, Malkin MG, Reed E, et al: Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma.  Mayo Clin Proc1999; 74:137-145.
  175. Jatoi A, Dakhil S, Burch P, et al: A phase II trial of green tea for androgen-independent prostate cancer: a North Central Cancer Treatment Group (NCCTG) trial [abstract].  Proc Am Assoc Cancer Res2002; 43:492.
  176. De Smet PA: The safety of herbal products.   In: Jonas WB, Levin JS, ed. Essentials of Complementary and Alternative Medicine,  Philadelphia: Lippincott Williams & Wilkins; 1999:108-147.
  177. Cassileth BR, Vickers AJ: Complementary and alternative therapies.  Urol Clin North Am2003; 30:369-376.
  178. Lagnado L: Laetrile makes a comeback on the web: long deemed illegal by the FDA, it's selling briskly again to desperate patients online.  The Wall Street JournalApril 22, 2000;
  179. Nortier JL, Martinez M-CM, Schmeiser HH, et al: Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi).  N Engl J Med2000; 342:1686-1692.
  180. Lord GM, Cook T, Arlt VM, et al: Urothelial malignant disease and Chinese herbal nephropathy.  Lancet2001; 358:1515-1516.
  181. Spencer Frame B, et al: Hypercalcemia and skeletal effects in chronic hypovitaminosis A.  Ann Intern Med1974; 80:44.
  182. Spencer JW: Complementary/Alternative Medicine: An Evidence-Based Approach,  Mosby, 1999.
  183. Albanes D, Heinonen OP, Huttunen JK, et al: Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence.  Am J Clin Nutr1995; 62(6 suppl):1427S-1430S.
  184. Kaptchuk TJ: Acupuncture: theory, efficacy, and practice.  Ann Intern Med2002; 136:374-383.
  185. Meeker WC, Haldeman S: Chiropractic: a profession at the crossroads of mainstream and alternative medicine.  Ann Intern Med2002; 136:216-227.
  186. Nielsen Net Ratings Global Intenet Usage.  Available at http://www.nielsennetratings.com/2002
  187. Hellawell GO, Turner KJ, Le Monnier KJ, et al: Urology and the Internet: an evaluation of Internet use by urology patients and of information available on urologic topics.  BJU Int2000; 86:191-194.
  188. McFarlane N, Parker JH, Denstedt JD: Urology and the Internet.  Contemp Urol1999; 11:38-40.
  189. Chen X, Siu L: Impact of the media and the Internet on oncology: survey of cancer patients and oncologists in Canada.  J Clin Oncol2001; 19:4291-4297.
  190. Smith RP, Devine P, Jones H, et al: Internet usage by prostate cancer patients undergoing radiation therapy.  Urology2003;
  191. Vordermark D, Kolbl O, Flentje M: The Internet as a source of medical information. Investigation in a mixed cohort of radiotherapy patients.  Strahlenther Onkol2000; 176:532-535.
  192. Yakren S, Shi W, Thaler H, et al: Use of the Internet and other information resources among adult cancer patients and their companions [abstract].  Proc Am Soc Clin Oncol2001;1589.
  193. Bernstam EV, Kamvar SD, Meric F, et al: Oncology patient interface to Medline [abstract].  Proc Am Soc Clin Oncol2001;974.
  194. Berland GK, Elliott MN, Morales LS, et al: Health information on the Internet: accessibility, quality, and readability in English and Spanish.  JAMA2001; 285:2612-2621.
  195. Meric F, Bernstam EV, Mirza NQ, et al: Breast cancer on the World-Wide Web: determinants of web site popularity [abstract].  Proc Am Soc Clin Oncol2001;1904.
  196. Metz JM, Devine P, DeNittis , et al: A multi-institutional study of Internet utilization by radiation oncology patients.  Int J Radiat Oncol Biol Phys2003; 56:1201-1205.