Complementary and Alternative Medical Therapies in Pediatric Oncology

Thomas W. McLean

Kathi J. Kemper

INTRODUCTION

Pediatric oncologists routinely confront a variety of questions about integrating complementary and alternative medical (CAM) therapies with conventional care:

What kinds of complementary therapies might my patients be using, and how do I find out?
What are the potential risks and benefits of combining CAM and conventional treatments?
How do I answer a parent’s question about boosting the immune system with natural products?
What natural approaches can a family use to help reduce the child’s side effects and optimize their overall health?
Are there special diets or foods a child should eat, or not eat, during cancer therapy?
Where do I turn for reliable, evidence-based information about complementary therapies?
How can I distinguish between legitimate and “quack” therapies?

When faced with such questions, a pediatric oncologist should provide positive reinforcement to families for asking, and approach it as an opportunity to engender trust and educate families, because many patients and families use CAM but do not tell their physicians. Understandably, families want to do everything they can to help their child recover from cancer and to reduce their future health risks. Physicians need solid scientific evidence to provide comprehensive advice. They need to elicit a complete history of the different therapies families are considering (or are already using) for their child, understand basic information about CAM practices and CAM providers, and know where to turn for additional information. This chapter provides an overview of CAM in pediatric oncology. Other chapters in this text cover closely related topics such as nutrition (Chapter 41), symptom management (Chapter 42), psychosocial support (Chapter 45), and ethical considerations (Chapter 47).

DEFINITIONS

Complementary therapies are used in conjunction with mainstream medical therapies. Examples include dietary supplements, massage, guided imagery, biofeedback, and hypnosis. These therapies are not replacements for medical regimens for serious medical problems but are offered to support the patient and family. Alternative medicine refers to therapies used in place of mainstream medical therapies; for example, using prayer or spiritual healing to replace chemotherapy. The term Complementary and Alternative Medicine is used by the National Institutes of Health’s National Center for Complementary and Alternative Medicine, but is being replaced in the popular media and some professional organizations (such as the Consortium of Academic Health Centers for Integrative Medicine) by the terms holistic and integrative medicine.

Holistic medicine refers to care of the whole patient—body, mind, emotions, spirit, and relationships—in the context of the patient’s values, beliefs, family, culture, and community. Integrative medicine refers to health care that focuses on wellness and health promotion, combining complementary with mainstream therapies based on scientific evidence in the context of patient- and family-centered comprehensive care. Families who use complementary therapies (prayer, massage, dietary changes, and guided imagery) along with chemotherapy are using an integrated approach.

EPIDEMIOLOGY

CAM use by pediatric oncology patients is common and has been reported from many countries and cultures. Geography and culture play important roles in CAM prevalence and types. Table 53.1 lists the prevalence and most popular CAM therapies by location. Some studies, but not all, have associated CAM use with older patient age, worse prognosis, use of CAM by a parent or other family member, longer time since diagnosis, higher parental education level, and higher family income. Most CAM users perceive CAM therapies as beneficial and safe. The use of CAM by children with cancer ranges from 6% to 91% depending on definitions of CAM and how the questions are asked. Worldwide, herbal remedies appear to be the most widely used CAM therapy, followed by dietary changes and faith healing.¹ CAM use is also common in the palliative phase of therapy²^,³ as well as in survivors of pediatric cancer, often to alleviate long-term symptoms from the cancer or its treatment.⁴^,⁵

Studies consistently report that many patients and families do not report CAM use spontaneously, so clinicians should inquire routinely about all the therapies patients are using. Many pediatric oncologists, however, do not ask about CAM use, primarily due to a lack of time and knowledge.⁶ Many institutions, state agencies, and professional organizations do not have policies regarding the use of CAM in children.⁷ Even when hospitals have policies in place, there is wide variation in policy quality and practice.⁸ The Joint Commission now requires asking about over-the-counter medications, vitamins, and supplements as part of medication reconciliation, a component “Meaningful Use.”⁹ Many patients use more than one CAM therapy, but may not consider their use of this therapy as “CAM.” For example, many families pray, take vitamins, give back rubs, or drink herbal teas without thinking of these as CAM remedies. It is thus useful for clinicians to give examples of CAM by including phrases like “vitamins” and “teas.” Prayer, mind-body therapies (MBTs) (such as relaxation and guided imagery), dietary supplements (including vitamins, minerals, and herbs), and massage are the most commonly used in North America.

PATIENTS’ AND FAMILIES’ REASONS FOR USING COMPLEMENTARY AND ALTERNATIVE MEDICINE

Families seek therapies that are consistent with their values and culture and seek care from therapists who respect them as individuals
and who offer them time and attention. Patients prize the care they receive from compassionate, comprehensive, empathetic clinicians who provide individualized care. They seek additional information on healthy lifestyle choices, dietary supplements, and other strategies over which they may exert some control and that may enhance the child’s resilience and reduce side effects of treatment. Families who use CAM therapies rarely abandon mainstream care. They largely support communication between their child’s physician and CAM practitioners,¹⁰ although bidirectional communication is rare.¹¹

Mainstream and complementary therapies tend to emphasize different primary outcomes or goals. Mainstream therapies are geared toward specific, problem-oriented outcomes such as curing the cancer, managing symptoms, and preventing specific problems (such as secondary infections). Many complementary therapies, on the other hand, promote the patient’s overall well-being and resilience, and secondarily improve symptoms.

TABLE 53.1 Prevalence and Most Popular CAM Therapies in Pediatric Oncology by Location

Location	Overall Prevalence	Most Popular CAM Therapy	Reference
New York City (US)	84%	Dietary changes	60
Washington State (US)	73%	Dietary supplements	116
North Carolina (US)	47%	Prayer/spiritual healing	117
Canada (western and central)	61%	Vitamins and minerals	118
Mexico	70%	Herbs	19
Guatemala	90%	Dietary changes and herbal supplements	119
Germany	35%	Homeopathy	120
Netherlands	42%	Homeopathy	121
Italy	12%	Homeopathy	122
Ireland	57%	Vitamins and minerals	123
Turkey	77%	Nettle	124
Israel	61%	Traditional Arabic and Middle Eastern treatments	125
Jordan	65%	Herbs	126
Lebanon	15%	Dietary supplements	127
Malaysia	85%	Water therapy	128
Singapore	67%	Dietary changes	129
Taiwan	73%	TCMs	130

Few children take supplements to prevent primary tumors. However, children who have one malignancy are at increased risk of later developing other malignancies, and as these children/young adults grow older, they may be interested in taking supplements to reduce their subsequent risks. Common and well-accepted cancer risk factors in adults include tobacco use, excessive alcohol use, excessive sun exposure, poor nutrition, obesity, physical inactivity, some infections (human papilloma virus, hepatitis B) and unsafe sex.¹² These well-established risk factors should definitely be avoided by patients to minimize the risk of secondary malignancies.

Conventional therapies for children with cancer may be arduous and often have debilitating side effects. Treatment complications are accepted by most families because they are optimistic that standard treatments will cure the cancer. However, as treatments affect the child’s quality of life, many parents look toward other therapies to help the child feel better. The most common reasons for CAM use include to treat or cure the cancer itself, to help with symptom management, and to support ongoing use of conventional therapy.¹ If conventional therapies are unsuccessful, parents often begin searching for any therapy that might offer hope of a cure.¹³

Talking with Patients and Families

The primary reasons that families do not communicate about their use of CAM therapies include concerns about a negative response from physicians, the belief that physicians do not need to know about CAM use, and that they are not asked.¹⁴ Thus, it is important for physicians to initiate discussions in a systematic fashion. The American Academy of Pediatrics (AAP) has published guidelines for counseling families who choose CAM therapies (Table 53.2).¹⁵^,¹⁶ Clinicians should assess the patients’/family’s goals, types of therapies under consideration, source of recommendations and information, the family’s opinion about and experience with it, and their interest in learning more or pursuing the therapy.

Having a ready supply of patient information materials about the more commonly used therapies and therapists is valuable in addressing common concerns and helping patients distinguish between evidence-based and market-driven therapies. The AAP has published a brochure for families about complementary and integrative medicine; the pamphlet encourages families to talk with their clinician about all the therapies they are using (posters and other resources to encourage families to talk with their clinician about CAM are available from the NIH NCCAM, http://nccam.nih.gov/timetotalk/, the Canadian Pediatric Society, http://www.pedcam.ca/resources, and the AAP: http://www2.aap.org/sections/chim/CamPoster07Eng.pdf, and http://www.healthychildren.org/). Additional evidence-based resources are listed in Table 53.3. It is also helpful to collaborate with hospital and medical center librarians, pharmacists, and nutritionists. There may be additional resources within the institution, such as nurses or physical therapists who practice therapeutic massage or therapeutic touch (TT). Families have far more respect for a physician whose response to a question about an alternative therapy is “I don’t know, but I’ll do my best to find out to help your child,” than to a physician who ignores, disparages, or dismisses their questions.

By better understanding the patient and family viewpoints, experiences, and expectations and by anticipating common questions and informational needs about specific treatments, the
physician can offer better advice in a focused, efficient manner. Even after learning about a family’s particular interest in complementary therapy, it is wise to step back and ask in a systematic fashion about all the other therapies the family may have considered before rushing in to offer advice.

Families facing a crisis may be more susceptible to testimonials, misleading claims, and quackery than other families. The internet is a rich source of evidence-based guidelines, but it can also introduce families to deceptive claims.¹⁷^,¹⁸ The resources included here (Table 53.3) should prove helpful to health care providers and families.

TABLE 53.2 Counseling Families Who Choose an Integrative Approach to Cancer Care

Ask families systematically about different therapies the patient may be using. Use examples when possible. Rather than asking about “alternative” therapies, the clinician should ask about the use of “vitamins, herbs, supplements, teas, homemade remedies, back rubs, chiropractic, acupuncture, or other services” to enhance health. It is also useful to ask how the patient manages stress; examples may include exercise, prayer, music, or talking with friends or trusted adults
Identify the health goals of the patient and family
Be sensitive to and respectful of families’ values, culture, and education level. Do not be dismissive about their interest in complementary therapies or folk remedies. Be empathetic and listen actively
Recognize feelings of being threatened and guard against becoming defensive or confrontational
Seek information from reliable sources about the therapies of interest
Evaluate scientific merits of specific therapies for specific problems or specific outcomes. Do not “lump” all complementary therapies or all goals together. Herbs are not equivalent to massage. The goal of cure is not the same as a goal of knowing one has explored all reasonable options to help
Identify risks or potential harmful effects including interactions with medications
Provide information to families about a range of options including common use, evidence of benefits, and evidence of risk
Regardless of the family’s choices, offer to assist in monitoring and evaluating the response to treatment
If feasible (and with the permission of the family), coordinate care of CAM providers in the overall care of the patient

Modified from Kemper KJ, Vohra S, Walls R; American Academy of Pediatrics. The use of complementary and alternative medicine in pediatrics. Pediatrics 2008;122:1374-1386; Committee on Children With Disabilities. American Academy of Pediatrics: counseling families who choose complementary and alternative medicine for their child with chronic illness or disability. Committee on Children With Disabilities. Pediatrics 2001;107:598-601.

TABLE 53.3 Evidence-Based Internet Resources for CAM Therapies

AAP	Section on Complementary and Integrative Medicine http://www2.aap.org/sections/chim/
CAHCIM	Consortium of Academic Health Centers for Integrative Medicine http://www.imconsortium.org/home.html
Academic Sites	M.D. Anderson Cancer Center site Complementary and Integrative Medicine Educational Resources: http://www.mdanderson.org/departments/cimer/ Memorial Sloan Kettering Information about Herbs, Botanicals and Other Products: http://www.mskcc.org/mskcc/html/11570.cfm PedCAM Network: http://www.pedcam.ca/
Government Sites	National Cancer Institute’s page on Complementary and Alternative Medicine: http://www.cancer.gov/cancertopics/cam National Center for Complementary and Alternative Medicine: http://www.nccam.nih.gov/ National Library of Medicine page on dietary supplements and complementary medicine: http://www.nlm.nih.gov/services/dietsup.html NIH Office of Dietary Supplements: http://ods.od.nih.gov/
Other Nonprofit Sites	The American Cancer Society—complementary and alternative therapies http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/complementary-and-alternative-medicine-landing
Subscription Information	ConsumerLab, independent testing of the quality of herbal and dietary supplement products: www.consumerlab.com Natural Medicine Comprehensive Database, produced by the publishers of Prescriber’s Letter: http://www.naturaldatabase.com/

CAM THERAPIES

The types and number of potential therapies available to patients and promoted in the media can be overwhelming. It is helpful to use written or electronic forms to collect information systematically and to request that families bring all the medications and other remedies they are using to appointments so they can be reviewed. Therapeutic options may be considered in four major categories: (a) biochemical, (b) lifestyle, (c) biomechanical, and (d) bioenergetic, which are distinguished by their mechanism of action or traditional use. Each of these major categories has several subcategories, some that may be considered mainstream and others that may be considered complementary, depending on cultural circumstances and definitions. For example, within the general category of biochemical therapies are medications (both prescription and nonprescription), herbs, vitamins, and other dietary supplements. The quality and quantity of evidence about the different biochemical therapies vary, but the purported mechanism of action (biochemical effects) is similar.

Lifestyle therapies include nutrition, exercise, sleep, stress management, and promoting healthy relationships and environments. Biomechanical therapies include diverse treatments whose mechanism of action includes some mechanical effect; these include surgery, physical therapy, massage, and chiropractic. Bioenergetic therapies are also diverse, but similar in terms of their belief in the relationship between a powerful invisible spirit (God) or life
energy (chi) and health; these therapies include prayer, acupuncture, Reiki, TT, and homeopathy.

Biochemical Therapies

Vitamins, minerals, herbs, hormones (such as melatonin), and other dietary supplements are commonly used natural products. One factor complicating care in this area is the dynamic and ever-changing nature of the therapies families are using as a result of information technology, economic forces, and popular culture. Oncology patients, desperate for a cure or “natural” therapy to complement conventional therapy, are particularly vulnerable to marketing claims of efficacy. Reliable sources of information are vital to address patient questions.

Herbs and dietary supplements are among the most commonly used complementary therapy in pediatric oncology patients (Table 53.1), with reported prevalence rates as high as 69%.¹⁹

Relatively little research has been done to rigorously assess the safety and efficacy of dietary supplements for pediatric oncology patients. Preclinical evidence based on in vitro data does not always correlate to in vivo efficacy. Also, the vast majority of studies evaluating the efficacy and safety of these therapies has been conducted in adults, and may not apply to children. Of note, even for randomized clinical trials published in the medical literature, caution must be exerted because most have not confirmed the quality of the supplement tested.²⁰

Dietary supplements with multivitamins and minerals are commonly used by children with and without cancer and other diseases.²¹ The AAP recommends supplemental iron and vitamin D to prevent iron deficiency and rickets, but it is unknown if they have cancer-preventing properties in children. In adults, vitamin D levels and vitamin D supplementation have provided conflicting results in regard to cancer risk.²² Because vitamin D can be synthesized by the skin in response to ultraviolet light, controversy has developed regarding the optimal amount and source of vitamin D (dietary vs. sun exposure).²³ The Institute of Medicine (IOM) and AAP currently recommend that children have a recommended daily allowance (RDA) of 400 IU of vitamin D during the first year of life, and 600 IU vitamin D per day beginning at age 1 year and continuing into adulthood, as well as a calcium at 700 to 1,300 mg per day depending on age.²⁴ In a large study in adults, however, supplemental calcium intake was associated with an increased risk of death from cardiovascular disease in men (but not women).²⁵ Several clinical trials are in progress to further evaluate the roles of vitamin D and calcium in cancer.

Most trials designed to assess cancer prevention by supplementation have not shown benefit. In one randomized clinical trial in adult males, the use of daily multivitamins modestly lowered the risk of total cancer, but not site-specific cancer or mortality.²⁶ In one epidemiologic study in children, supplemental vitamin administration was associated with an increased risk of leukemia.²⁷ Supplemental vitamin E, vitamin A, and beta-carotene do not appear to prevent cancer, and in fact may be dangerous for certain patients.²⁸^,²⁹^,³⁰ Vitamin C has long been used to treat numerous conditions, and it remains one of the most popular vitamin supplements. Controversy about the efficacy of vitamin C in preventing and treating cancer persists despite a lack of clear evidence to date.³¹ Folic acid supplementation does not appear to increase or decrease the incidence of site-specific cancer in adults.³² Although the implications are not clear, differences in oxidative stress and antioxidant status have been noted in patients with sarcomas and neuroblastoma, compared to control subjects.³³^,³⁴

Supplemental vitamins may reduce some toxicities in pediatric oncology patients, but antioxidants could theoretically counteract the cytotoxic effects of radiation therapy and some chemotherapy and thus be detrimental.³⁵ Low levels of vitamin A, selenium, and tocoferol in children with cancer may increase the risk of febrile neutropenia.³⁶^,³⁷ Supplementation with vitamin C, vitamin E, and selenium may decrease high-frequency hearing loss caused by cisplatin.³⁸ Vitamin E may also reduce cisplatin-induced neuropathy.³⁹ Selenium may reduce the severity and duration of mucositis in adults undergoing hematopoietic stem cell transplantation.⁴⁰ Homozygous deletion of GSTM1, a gene coding for antioxidant enzyme activity, is associated with greater psychological distress (including anxiety and depression) in childhood medulloblastoma survivors.⁴¹

β-glucans are polysaccharides found in mushrooms and other edible sources. There are hundreds of mushroom species with purported immunomodulatory and antitumor properties. Multiple mechanisms of action have been proposed based on in vitro data. Despite mushrooms’ popularity both as a food and dietary supplement, there are limited data regarding their efficacy for the prevention and treatment of cancer and other conditions.⁴² However, they can certainly be consumed as part of a healthy diet rich in phytonutrients.

The consumption of soy products that contain the phytoestrogen genistein has been linked epidemiologically to decreased rates of some cancers.⁴³ Although soy products may be beneficial to cardiovascular and overall health, isolated soy protein supplements have not been shown to effectively prevent or treat cancer of the breast, endometrium, and prostate.⁴⁴ A theoretical concern exists about the potential for soy products to promote the growth of hormonally active tumors. However, evidence to date suggests that soy consumption does not adversely affect recurrence or survival in patients with breast cancer.⁴⁵ Other natural compounds with cancer-preventing properties in vitro include curcumin, luteolin, pomegranate, lycopene, ellagic acid, terpenes, n-3 polyunsaturated fatty acids, and ginkolide B.⁴³^,⁴⁶

Antineoplastons are peptides and amino acid derivatives originally isolated from human blood and urine, and are controversial cancer therapies. Several phase II trials involving pediatric patients with brain tumors have been published;⁴⁷^,⁴⁸ however, no large phase III controlled trials utilizing antineoplastons in children have yet been published.

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