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The Oncologist, Vol. 11, No. 7, 732-741, July 2006; doi:10.1634/theoncologist.11-7-732
© 2006 AlphaMed Press

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Clinical Pharmacology

Complementary and Alternative Medicine During Cancer Treatment: Beyond Innocence

Metin Tascilar, Floris A. de Jong, Jaap Verweij, Ron H. J. Mathijssen

Department of Medical Oncology, Erasmus University Medical Center Rotterdam—Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Key Words. CAM • Herbs • Interactions • Cancer • Regulation • Internet

Correspondence: Ron H.J. Mathijssen, M.D., Ph.D., Erasmus University Medical Center Rotterdam—Daniel den Hoed Cancer Center, Department of Medical Oncology, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Telephone: 31-10-4391-112; Fax: 31-10-4391-053; e-mail: a.mathijssen{at}erasmusmc.nl

Received March 22, 2006; accepted for publication May 10, 2006.


   LEARNING OBJECTIVES
Top
 Learning Objectives
Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
After completing this course, the reader will be able to:

  1. Explain why cancer patients use complementary and alternative medicine.
  2. Describe possible dangers of complementary and alternative medicine during cancer treatment.
  3. Advise patients on how to deal with complementary and alternative medicine before, during, and after conventional cancer treatment.

Access and take the CME test online and receive 1 AMA PRA Category 1 CreditTM at CME.TheOncologist.com


   ABSTRACT
Top
 Learning Objectives
 Abstract
Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
Nowadays, complementary and alternative medicine (CAM) is popular all over the world. Billions of dollars are spent in this booming business. For several reasons, young, female, educated, and higher socioeconomic class cancer patients, in particular, have shown interest in these agents. Unfortunately, besides direct (and sometimes serious) side effects, several CAM ingredients are capable of interfering with the metabolism of concurrently used drugs, which may render the therapeutic outcome of the subscribed drug unpredictable. In the case of anticancer drugs, with their usually narrow therapeutic window, this may have dramatic consequences and can lead to unacceptable toxicities in some cases or decreased therapeutic activity in others. Therefore, cancer patients should be warned for these possible interactions and be advised to discuss CAM use openly with their treating physician. The general concept that natural products are harmless should thus be changed into a more realistic and responsible attitude. A tightened legislation and regulation (including Internet advertising and sales) could play a crucial role in this awareness process. This should finally enable safe exploration of the potential advantageous aspects of CAM, while living with cancer.


   INTRODUCTION
Top
 Learning Objectives
 Abstract
 Introduction
Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
The umbrella term "complementary and alternative medicine" (CAM) is defined by the National Center for Complementary and Alternative Medicine (NCCAM) as "a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine; that is, medicine as practiced by holders of ‘medical doctor’ or ‘doctor of osteopathy’ degrees and their allied health professionals, such as physical therapists, psychologists, and registered nurses" [1]. Boundaries within CAM and between the CAM domain and that of the dominant system are not always sharp or fixed [2]. Despite vigorous attempts, a large number of alternative definitions are available as there is no consensus over a single definition (Table 1Go) [1–3]. However, all descriptions are pointing in the same direction, but with a focus on different aspects. CAM includes practices and ideas self-defined by their users as preventing or treating illness or promoting health and well-being. Our review article mainly focuses on herbal remedies, botanical medicine (phytomedicine), vitamins, minerals, antioxidants, and metabolites (concurrently) used by cancer patients. As published information on this topic is impressive, it is not our goal to supply a complete overview, but just to outline clinically relevant topics for the practicing clinician dealing with patients suffering from a malignancy.


   WORLDWIDE USE OF CAM
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
CAM is widely used among cancer patients throughout the world (Table 2Go). Because surveys vary in terms of definitions of CAM and of specific types of therapy included in questionnaires, the assessment of overall prevalence is somewhat complicated. Noninvasive therapies like acupuncture, chiropractic, massage, spiritual healing, meditation, and imagery are most common, but use of dietary supplements is rapidly gaining terrain [4–8]. As a result, the economic impact of CAM is enormous. In the U.S., it is estimated that expenditures for alternative medicine services increased 45% between 1990 and 1997 and were conservatively estimated at $27 billion in 1997, which was comparable with the estimated out-of-pocket costs for all U.S. physician expenditures [9]. This increase in expenditure was primarily attributable to an increase in the proportion of the population seeking alternative therapies, rather than an increased number of visits per patient. An Australian questionnaire of more than 3,000 people reported similar population-adjusted costs [10]. In 2000, increases of 120% and 62% were found in the costs of alternative medicines and therapists, respectively, and expenditure on alternative therapies was nearly four times the public contribution to all pharmaceuticals, since 1993. Recent retail numbers indicate about $5 billion a year of "herbal" sales in Europe alone, where expenses in Germany account for 40% of this number, followed by France and Italy [11]. Other large European countries, like the United Kingdom and Spain, distribute only a small proportion in contrast to Germany.

Reflecting the growing interest of the public, politicians, and professionals in CAM, the budget of the NCCAM, which is part of the National Institutes of Health (NIH), increased from $50 million in 1999 to more than $120 million in 2006 [12]. Although only a small percentage of overall costs are claimed, insurance coverage of CAM is also further expanding [6].

Based on retail sales, the best selling over-the-counter herbal supplements in the U.S. in 2002 were garlic (Allium sativum), ginkgo (Ginkgo biloba), and echinacea (Echinacea purpurea) [13]. The other herbs in the top ten were soy (Glycine max), saw palmetto (Serenoa repens), ginseng (Panax ginseng), St. John’s wort (Hypericum perforatum), black cohosh (Actaea racemosa or Cimicifuga racemosa), cranberry (Vaccinium macrocarpon), and valerian (Valeriana officinalis) [13, 14]. Other reports show that melatonin, coenzyme Q10, green tea extract, cell forte (inositol and inositol hexaphosphate), glucosamine, peppermint, EPA (fish oil), and ginger are also popular dietary supplements/ natural products (Fig. 1Go) [15, 16].

The majority of research on the use of CAM is conducted in the U.S., with multiple recent surveys suggesting that between 25% and 84% of U.S. cancer patients have used CAM therapies at some point after their diagnosis, with variations in utilization rates depending on geographic area and type of cancer (Table 2Go) [17–25].

In 1998, a systematic review by Ernst and Cassileth [26], including 26 worldwide surveys, showed an average percentage of 31% of CAM use among adult cancer patients, with a range of 7%–64%. This is largely in line with other studies (Table 2Go) [27–32]. A recent descriptive survey conducted in 14 European countries showed that 36% of cancer patients used some form of CAM, again with a wide range among countries of 15%–73% [33]. In an Australian population survey, there was an overall use of 52% of at least one nonphysician-prescribed alternative drug [10]. CAM is not only popular in Western societies, as is shown in a nationwide cross-sectional survey in Japan: in that study 45% (1,382 of 3,100) of cancer patients used some form of CAM [34]. In a population-based sample of 1,065 Chinese women with breast cancer, nearly all women(98%)reported use of CAM after diagnosis [35].


   REASONS FOR CAM USE
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
There are specific cancer-related reasons for using CAM. A Canadian survey of more than 900 cancer patients demonstrated that 94% experienced disease-related symptoms such as fatigue and anxiety that were not addressed by their conventional treatment [36]. Most cancer patients, in general, were satisfied with the conventional treatment they received for their cancer. Nonetheless, they were more likely dissatisfied with the attention paid to their symptoms and side effects. A second reason for CAM use is the presumed action as an anticancer agent (e.g., PC-SPES, used by prostrate cancer patients) [37, 38]. Several CAM products are under investigation in clinical trials for this reason; however, they have not been under appropriate trial development so far [39].

CAM is used for its cancer preventive properties as well. An ideal preventive agent has little or no toxicity, high efficacy in multiple sites, capability of oral consumption, a known mechanism of action, low cost, and above all, general acceptance [40]. For example, more or less conscious use of green tea by men has gained its place in society. Indeed, in a recent case-control study a protective effect of green tea against prostate cancer was suggested [41], which is supported by in vitro research [40, 42]. The risk was thought to decline with increasing frequency, duration, and quantity of green tea consumption. However, it should be noted that conflicting results are reported by epidemiological studies on the use of green tea as a protective substance in relation to prostate cancer [41].

In addition to these reasons, cancer patients, in general, have the same reasons as other people for using CAM [43–45]. Disease-related symptoms not easily addressed by conventional treatment and concerns about the adverse effects of chemical/pharmaceutical medicines are some of them [4]. Also, an increased need for more personalized health and a greater public access to health information (i.e., the Internet) and popular media attention to CAM fuel its increasing use in many industrialized countries [9, 26, 34]. In addition, quality of life may also be a reason for CAM use [46]. However, results are conflicting regarding the self-reported quality of life among CAM users versus nonusers. In a recent report, a study performed at a community hospital comprehensive cancer center was described, which found a better quality of life among dietary supplement users compared with nonusers [46]. In contrast, earlier data showed opposite results [20, 47, 48]. It should be mentioned that these findings are not completely comparable because the latter studies used a broader definition for CAM.

In particular, CAM use appears to be more common among those with higher income, higher educational level, younger age, female gender, or history of CAM use [4, 9, 34, 48]. Also, cancer patients resort to CAM more frequently than patients with acute or chronic diseases, which are not malignant, probably explained by the reasons mentioned before [49]. In addition, use of chemotherapy and advanced disease are correlated with more frequent CAM use [4, 9, 34, 48]. A recent study describing the prevalence of CAM use in patients enrolled in early-phase chemotherapy trials at the Mayo Clinic Comprehensive Cancer Center showed a high use of such products [50]. More than 80% of patients simultaneously used pharmacologic CAM (like vitamins, herbs, and minerals) in addition to their experimental chemotherapeutic agents [50], which is (currently) often an exclusion criterion and/or formally not allowed during this type of treatment. Additionally, a recent study in nearly 500 cancer patients revealed that 65% of the 131 patients being treated with chemotherapy alone said they used CAM in conjunction with their chemotherapy, whereas "only" 35% of the 142 patients receiving radiotherapy reported CAM use [25].

Colorectal and breast cancer patients, in particular, seem to be likely to use dietary supplements, compared with lung cancer patients [51, 52]. An increased perception of the risk of cancer recurrence and cancer-related death are associated with CAM use by breast cancer patients, as concluded in a study by Rakovitch et al. [52]. In contrast, in another recent study, it was concluded that CAM users are less likely to believe they will die from breast cancer [53]. In both studies, no relationship between CAM use and anxiety and/or depression could be found. This is noteworthy because both anxiety and depression are frequently mentioned as an important explanation for the more frequent use of CAM, in particular CAM influencing mood (like St. John’s wort or medicinal cannabis) [54–57].

Most cancer patients combine, rather than replace, conventional therapy with CAM [4,6,20,44,58]. This is clearly demonstrated in a survey by Cassileth et al. [44], in which 304 in-patients of a cancer center and 356 patients under the care of unorthodox practitioners were interviewed. Of all patients studied, 8% never received any conventional therapy, and 54% of patients on conventional treatment also used unorthodox treatments.


   DANGERS OF CAM USE
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
As concluded from a recent report that was based on in-person interviews with prostate cancer patients, CAM users consider CAM as safe and holistic [59]. Meanwhile, this is coupled with a perception of conventional medicine as being an aggressive and isolated treatment for their cancer. Users report a belief in the potential efficacy of CAM, even if they are aware of the lack of any (scientific) evidence. Although nonusers expressed similar concerns about side effects of conventional treatment and considered CAM harmless as well, they assigned different priorities to these issues in their decision making [59]. Seidl and Stewart [60] interviewed 13 menopausal women who were experiencing symptoms attributed to menopause and were using alternative therapies. Because of their "natural" origin, the women perceived the alternative treatments to be safe.

In spite of such common perceptions in the community (both patients and physicians), there is accumulating evidence indicating that not all CAM is free from harm. There are concerns regarding direct adverse events, for example, allergic reactions (urticaria, angioedema, skin reactions), and gastrointestinal complaints [61]. Among others, hepatotoxicity and neurotoxicity have also been reported for popular herbs [61]. For instance, greater celandine (Chelidonium majus) preparations, frequently used for gastrointestinal discomfort, may induce mild to severe forms of acute (cholestatic) hepatitis [62]. The Chinese herbs Stephania tetrandra and Magnolia officinalis, used in weight-loss pills, are associated with nephropathy-like interstitial renal fibrosis [63–65]. As a result of the replacement of S. tetrandra by a botanical known to contain aristolochic acid, Aristolochia fangchi, possibly as a consequence of a manufacturing error, products containing this herb have even been associated with induction of urothelial carcinoma, because A. fangchi is nephrotoxic and carcinogenic [66]. In addition, the effect of most CAM on the unborn child is unknown in most cases, although its use by pregnant women is frequent [61].

Product quality of CAM is highly variable, with varying concentrations of its major and characteristic ingredients [61]. This appears to be the case both in countries where no strict regulation for these products exists (e.g., the U.S.) and in countries where stricter regulation has been formulated (e.g., Germany) [61]. In addition, pollution with pathogenic micro-organisms, pesticides, heavy metals, etc., is no exception, which makes health risks even higher [61]. For example, for cannabis, which can be used for palliative purposes by cancer patients [56], it was recently demonstrated that cannabis bought in Dutch "coffee shops" can be contaminated by bacteria and fungi that may harm seriously ill patients [67]. Micro-organisms found included Escherichia coli and several Penicillium, Cladosporium, and Aspergillus species. To avoid risks associated with pollution, users of CAM should be extra careful, because herbs that seem safe under normal conditions for healthy people may be not be so safe for certain patient groups (such as cancer patients) [54].

Beside these direct side effects, CAM has the potential to interact with (anticancer) drug metabolism. Interactions between CAM and commonly prescribed drugs have been studied extensively and reported in detail [54, 68, 69]. Interactions between CAM and anticancer agents are currently less well documented. For St. John’s wort, an herbal product thought to have a mild antidepressant action, interactions with irinotecan (Camptostar®; Pfizer Pharmaceuticals, New York), imatinib (Gleevec®; Novartis Pharmaceuticals Corporation, East Hanover, NJ), and docetaxel (Taxotere®; sanofiaventis, Bridgewater, NJ) have been studied [70–72]. Recently, the effect of milk thistle (Silybum marianum; used for its tonic, demulcent, and antidepressant effects) on irinotecan pharmacokinetics was also described [73]. Currently, research is ongoing, for instance to study the effects of medicinal cannabis on irinotecan and docetaxel metabolism [74]. Clinically significant interactions were seen in some of these cases, as shown in more detail in the accompanying article by Meijerman et al. [75] in this issue of The Oncologist. Although not studied in detail yet, potential interactions with anticancer agents may also be expected for compounds other than the ones just mentioned, like echinacea, garlic, ginkgo, ginseng, and kava (Piper methysticum) [13]. Basically, interactions are mostly thought to be the result of interactions at the enzymes level (like those of the cytochrome P450 metabolic pathways) and drug-transporting proteins (ATP-binding cassette transporters), which can be influenced in activity and expression by CAM ingredients [75]. If given together, some CAM may indirectly induce the metabolism of cytotoxic agents, potentially leading to nontherapeutic systemic drug levels. In addition, other CAM may inhibit the metabolism of cytotoxic agents, leading to potentially lethal toxicities if the metabolic step inhibited inactivates the given drug. Taking into account that a relatively high percentage of patients participating in phase I trials seems to use CAM [50], without notifying their physician on this fact, this could have serious (negative) consequences for both participating patients and for the development of new anticancer agents.

Additionally, because most CAM contains (several) constituents with unknown pharmacological capacities, the effect of the combination with conventional or experimental treatment may be totally unpredictable. For instance, in the case of St. John’s wort, ingredients with inhibitory and inducing capacities are known, and depending on the amount of the individual components, the interactive effect may totally differ. Apart from this, the duration of intake of this herbal product is also thought to influence the type of effect (first inhibition, later on induction) on drug-metabolizing and transporting proteins [76], further decreasing the possibility of predicting the occurrence of undesired clinical effects.


   QUALITY CONTROL
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
European and U.S. Legislation
In 1999, a European Community (EC) directive came into effect that made it easier to get marketing authorization for herbal medicines for which "well-established" data on efficacy and safety are available [11]. Five years later, another directive was implemented, which made it possible to also register traditional herbs that had been used for more than 30 years (and also for at least 15 years in the EC) not meeting the criteria for the group of preparations mentioned above [11]. All other compounds are regulated as "food" products. For registration, a special committee evaluates the herbals and, after acceptance, it lists its manufacturers, indications, doses, routes of administration, etc. [11]. Health authorities are capable of labeling these products with advice for proper use. These procedures will increase the transparency of CAM, and the "quality check" will stimulate companies to meet registration criteria and consumers to use registered products. As mentioned earlier, this does not mean that there are no caveats left, as, for instance, concentrations of characteristic constituents may still vary substantially among products available on the market [77]. Unfortunately, it also leads to confusing situations in which herbs are sold both as medicines and food products, with their own regulations, which is, for instance, currently the case for herbal teas.

The introduction of medicinal cannabis to the Dutch drug market nicely illustrates the above-mentioned regulation. In more and more countries, including some parts of the U.S., production (at home) and use of cannabis for medicinal purposes is tolerated or even legally permitted [56, 78]. As in other countries, The Netherlands has established a national agency on medicinal cannabis (the Office of Medicinal Cannabis), under whose responsibility a standardized cannabis product for medical treatment purposes is produced and distributed [79]. The variants produced are not contaminated by micro-organisms [67], and their legal availability meeting pharmaceutical quality opens doors to initiate well-designed clinical trials investigating safety and efficacy. Because there are a lot of gaps in our knowledge on fundamental questions related to the administration of medicinal cannabis, such issues need to be resolved urgently [56, 80].

In the U.S., the Food and Drug Administration (FDA) regulates foods, drugs, and cosmetics in interstate commerce [11]. As a result of the 1994 Dietary Supplements Health Education Act, manufacturers are allowed to distribute their dietary supplements without proven safety and efficacy, as long as they do not claim a link between their product and a specific disease [81]. Meanwhile, they may, for instance, make structure/function claims, still without proof of safety and efficacy. This act has led to an enormous growth in the market for dietary supplements [81]. The FDA has no authority to approve or analyze these products before they are brought to the market [82]. In the U.S., it has also been proposed to change the regulations, including requirements that all health claims be supported by data approved by the FDA, and that an accurate list of ingredients is provided on the product label [82].

Even more important than federal rules, state laws control much of CAM practice. As a result, regulations may vary from state to state and mainly involve health care license, scope of practice, and malpractice. In 2004, fewer than one third of all states had health freedom laws or regulations protecting patient access to CAM [83]. In most states with health freedom laws, these laws/regulations protect the patient’s right to access CAM offered by licensed physicians, but not by all other CAM practitioners [83].

Internet
In addition to articles and advertisements in papers and magazines and on television and the radio, in recent years, the role of the Internet as an easily accessible source for knowledge has rapidly emerged. The Pew Internet Project for Health reported that more than 60% of people who used the Internet were looking for health information, half of whom were looking for information on CAM [84]. Analysis of several U.S. nationwide representative datasets revealed that people who seek online health information were more frequently female, were frequently not full-time employed, were frequently engaged in other Internet activities, had more specific health reasons (diagnosed with new health problem, ongoing medical condition, prescribed new medication or treatment), and/or were helping another person deal with health issues [85]. About half of the Pew survey respondents found credibility in what they read, saying that they thought that almost all or most information they had found on the Internet was reliable [84]. However, information on the Internet is not always as reliable as patients may think, which imposes a serious risk to patients vulnerable to misleading information. Moreover, medical products, and in particular CAM, can easily be purchased on the Internet without a prescription.

As demonstrated in various studies, the quality of Web sites on CAM varies enormously. Content quality is often poor and a shocking and surprising amount of misinformation regarding CAM for cancer can be found on the Internet [86, 87]. Recently, Schmidt and Ernst [88] investigated 32 Web sites to evaluate the quality of information on CAM, among others, for cancer. They concluded that the majority of evaluated Web sites provided valuable and reliable information, especially for the prevention of cancer. However, several web sites issued information on CAM that is, in the least, misleading. Five of the 32 investigated Web sites gave information biased in favor of its own products or services, and only 10 gave references to scientific literature. Some Web sites even promoted and discussed CAM treatments (like shark cartilage, the Gerson’s diet, and mistletoe [Viscum album L]), for which no compelling safety and efficacy data could be found in regular medical databases. A few sites were outright dangerous, as they advised patients against using conventional therapies [88].

Using another approach, Morris and Avorn [89] investigated the Internet for eight widely used herbal supplements. Eighty-one percent of the 338 investigated retail Web sites made at least one health claim. More than half of them claimed to treat, prevent, diagnose, or cure specific diseases. Despite regulations prohibiting such claims without the FDA’s disclaimer, of all sites with a health claim, more than half omitted the standard federal disclaimer. Additionally, on average, only 28% (both retail and nonretail sites) provided referenced information [89].

As concluded by many researchers [88, 90], there is an urgent need to raise public awareness about the quality of Web sites on CAM and about the usefulness of Internet information. Major cancer organizations and other impartial interest groups should investigate Web sites and create and administer a seal of approval, for safety and reliability [88]. Morris and Avorn [89], as do others [81], take a step further; they conclude that in this era of evidence-based medicine, more effective regulation and vigilance are required to put CAM on the same basis as other medicinal products.


   CLINICAL IMPLICATIONS AND RECOMMENDATIONS
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
As stated before, CAM use among cancer patients is substantial, and potential interactions with (conventional or experimental) chemotherapy should make the clinician aware of the dangers. As a result, it is of utmost importance to clarify its use before exposing patients to drugs with a narrow therapeutic window, like most anticancer agents [91]. Because patients may, for instance, be ashamed to openly admit CAM use to their treating physicians, true use may be underestimated [92, 93]. On the other hand, others say that reports of prevalence are often exaggerated, as surveyors may use a different definition of CAM [94]. In clinical practice, in every patient contact, the clinician should keep in mind that most (cancer) patients will not spontaneously report CAM use. A previously mentioned study revealed that, of the 48% of cancer patients using concomitant CAM (median two CAMs per patient), a vast majority did so without their doctor knowing [25].

Herbal products are commonly perceived as "natural" and therefore as "innocent," a perception that is hard to change [95]. As a consequence, denial on purpose is most often not the case because patients may not realize the seriousness of CAM use and will thus answer "no" if asked for concurrent drug use [45]. This is illustrated by the example of St. John’s wort tea. Some herbal teas, like the St. John’s wort variants, are produced by companies regarded as highly reliable and trustworthy in the community and sold in the supermarket as tea. Patients may drink this tea at home, not explicitly being aware of the associated risks they would avoid if they had to buy such a product in their local pharmacy or drugstore. The physician should therefore actively ask for herbal and supplement use, while explaining their potential hazards [4, 54]. An objective and nonjudgmental attitude of the medical doctor is clearly essential to encourage patient disclosure [4, 54]. Patients should not get the feeling of being accused of use CAM, but should explicitly be advised to avoid CAM prior to and during (chemo)therapy. If such avoidance is not possible, the consequences for therapy should be evaluated in detail. Clearly, governments, cancer organizations, and patient organizations also have their responsibilities to achieve this common goal. Likewise, the risks associated with the use of the Internet as an information source for and retailer of CAM, whether as preventive, curative, or palliative treatment, should be more explicitly brought to the attention of cancer patients.

Meanwhile, we should not disqualify CAM use per se. CAM therapies such as acupuncture, meditation, and music therapy can be beneficial for cancer patients [96–98]. There is evidence to support some of the CAM approaches, in particular in the symptom management and supportive care of cancer patients [99]. They may control symptoms and enhance quality of life [5, 56]. More and more medical centers now develop programs that integrate conventional medicine with complementary approaches that have some high-quality scientific evidence of safety and effectiveness [94]. The term "integrative oncology" has been created for this combination [94]. Hopefully, more research in this field of science will help more patients and treating physicians to further explore effective and safe approaches and become aware of the existence of the possible dangers, as both conventional treatment and CAM have found a prominent place in modern society.


   AUTHORS’ NOTE
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
Disclosure of Potential...
 References
 Additional Reading
 
Metin Tascilar and Floris A. de Jong contributed equally to this work.


   DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
References
 Additional Reading
 
The authors indicate no potential conflicts of interest.


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  		Table 1. Commonly used definitions of complementary and alternative medicine (CAM)

 

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  		Table 2. Impression of prevalence of complementary and alternative medicine (CAM) use by cancer patients worldwide

 

Figure 1
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  		Figure 1. Use of popular natural products among adults in the U.S. Data are derived from the 2002 edition of the National Health Interview Survey conducted by the National Center for Health Statistics (NCHS) and 2004 data released by the NCHS and the National Center for Complementary and Alternative Medicine. Available at http://nccam.nih.gov/news/camsurvey_fs1.htm. The flowering echinacea (Echinacea purpurea) is printed as background.

 

   REFERENCES
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
Additional Reading
 
  1. National Center for Complementary and Alternative Medicine (NCCAM). The Use of Complementary and Alternative Medicine in the United States. Available at http://nccam.nih.gov/news/camsurvey_fs1.htm. Accessed March 3, 2006.
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  7. Cohen L, Warneke C, Fouladi RT et al. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma. Cancer 2004;100:2253–2260.[CrossRef][Medline]
  8. Yoo HJ, Ahn SH, Kim SB et al. Efficacy of progressive muscle relaxation training and guided imagery in reducing chemotherapy side effects in patients with breast cancer and in improving their quality of life. Support Care Cancer 2005;13:826–833.[CrossRef][Medline]
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   ADDITIONAL READING
Top
 Learning Objectives
 Abstract
 Introduction
 Worldwide Use of CAM
 Reasons for CAM Use
 Dangers of CAM Use
 Quality Control
 Clinical Implications and...
 Authors' Note
 Disclosure of Potential...
 References
 Additional Reading
 
    Deng D, Cassileth BR. Integrative oncology: Complementary therapies for pain, anxiety, and mood disturbance. CA Cancer J Clin 2005;55:109–116.[Abstract/Free Full Text]

    De Smet PA. Herbal remedies. N Engl J Med 2002;347:2046–2056 .[Free Full Text]

    Sparreboom A, Cox MC, Acharya MR et al. Herbal remedies in the United States: potential adverse interactions with anticancer agents. J Clin Oncol 2004;22:2489–2503.[Abstract/Free Full Text]

    Weiger WA, Smith M, Boon H, et al. Advising patients who seek complementary and alternative medical therapies for cancer. Ann Intern Med 2002;137:889–903.[Abstract/Free Full Text]




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