Bethesda Handbook of Clinical Oncology, 2nd Edition

Targeted Treatments and Complimentary and Alternative Medicine

44

Complementary and Alternative Medicine in Oncology

Patrick J. Mansky

Dawn B. Wallerstedt

Marc R. Blackman

National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland

During the last decade, patients with cancer have increasingly turned to complementary and alternative medicine (CAM) resources in an attempt to cure cancer, to provide relief from cancer-related symptoms, or to improve overall well-being and quality of life. Complementary and alternative medicine, as defined by the National Center for Complementary and Alternative Medicine (NCCAM), is a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine (1,2). Although some scientific evidence exists about some CAM therapies, for most therapies there are key questions that are yet to be answered through well-designed scientific studies—questions such as whether these therapies are safe and whether they work for the diseases or medical conditions for which they are used.

The list of what is considered to be CAM changes continually, as those therapies that are proven to be safe and effective become adopted into conventional health care and as new approaches to health care emerge (http://www.nccam.nih.gov/health/whatiscam/#1).

Scientific assessments of safety, efficacy, and mode of action are either fragmented or totally lacking for many CAM modalities and approaches.

THE DOMAINS OF COMPLEMENTARY AND ALTERNATIVE MEDICINE

NCCAM groups the CAM modalities into five major domains that are applicable to cancer-related CAM (see Fig. 44.1).

 

FIG. 44.1. The complementary and alternative medicine (CAM) domains. (Source:http://www.nccam.nih.gov/about/plans/2005/index.htm, accessed 3/17/2005, with permission.)

USE OF COMPLEMENTARY AND ALTERNATIVE MEDICINE IN PATIENTS WITH CANCER

CAM use in patients with cancer varies according to region, geographical location, gender, and disease diagnosis. This chapter focuses on the data available on cancer patients in the United States. The prevalence of CAM use in patients with cancer has been estimated to be between 7% and 54% (1).

Predictors of Use of Complementary and Alternative Medicine in Patients with Cancer

  • Higher educational status
  • White ethnicity

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  • Deteriorating health status
  • Women

Preferred Complementary and Alternative Medicine Modalities in Patients with Cancer

Following is a list of CAM modalities used frequently by cancer patients:

  • Herbs, dietary supplements, and minerals
  • Special diets
  • Spirituality
  • Meditation or mind–body work
  • Relaxation or guided imagery
  • Acupuncture
  • Healing touch
  • Support groups
  • Yoga

Patients with cancer who use CAM often utilize several CAM modalities concurrently.

Use of Complementary and Alternative Medicine and Treatment Expectations

Comparisons of the reasons for CAM use among patients with different cancer diagnoses show many similarities. Most of the patients with cancer use CAM hoping to:

  • Boost the immune system
  • Relieve pain
  • Control side effects related to disease or treatment.

Only a few patients include CAM in the treatment plan with curative intent (2).

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COMPLEMENTARY AND ALTERNATIVE MEDICINE APPROACHES TO CANCER TREATMENT

A diverse array of CAM approaches has been used in clinical practice for the treatment of cancer and cancer-related symptoms. A comprehensive review of existing CAM practices used in cancer is beyond the scope of this chapter. Rather, the focus is on a set of CAM modalities and approaches based on the following selection criteria:

  • Accessibility and availability within the United States
  • Existence of peer-reviewed published information on efficacy or treatment-associated clinical benefit
  • Components of the CAM cancer treatment spectrum commonly employed (based on published demographic data) as complementary modalities by health care professionals or requested by patients
  • Alternative medical systems approaches are not included in this chapter. There is a paucity of published data from controlled clinical trials on the efficacy of these approaches in the treatment of cancer. The interested reader is referred to the available literature and is encouraged to seek advice from trained experts in the field (3,4).
  • Biologics employed in the treatment of cancer are not discussed in detail in this chapter. Most biologics would be considered experimental from the perspective of available scientific evidence of activity in cancer. Some fall into the category of alternative medical systems. For some of the agents the interested reader is referred to the information available on the CAM Physician's Data Query (PDQ) Web site of the National Cancer Institute (NCI) at http://www.nci.nih.gov/cancerinfo/pdq/cam.
  • A separate section has been included in this chapter to address some emerging data on interactions between botanicals and drugs and on resources regarding ongoing clinical trials that are investigating the efficacy of CAM, and that may be available to interested cancer patients.

CAM therapies discussed in this chapter are grouped into the following categories:

  1. Cancer symptom management
  2. Diet/nutrition/supplements

Cancer Symptom Management

Acupuncture

Acupuncture and electroacupuncture are widely used in cancer symptom management. A number of acupuncture approaches are being practiced, including Chinese, Japanese, Korean, and French acupuncture.

According to the 1997 NIH Consensus Conference on acupuncture (http://www.dowland.cit.nih.gov/odp/consensus/107/107_statement.htm), existing evidence based on clinical trials suggests a beneficial role for acupuncture in the areas of chemotherapy-induced nausea/vomiting and dental pain, whereas the clinical evidence for efficacy of acupuncture in other settings remains limited.

Adverse effects:

Acupuncture is generally well tolerated. The most frequent side effects include minimal local bleeding or bruising and mild pain (5,6).

Caveats:

Acupuncture is not advisable in patients with:

  • Thrombocytopenia
  • Bleeding disorders
  • Aplasia

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Chemotherapy-induced Nausea and Vomiting

Commonly used acupuncture points include P6, Neiguan point of the pericardium meridian of hand (jueyin), and St 36, Zunsali point of the stomach meridian of foot (yang ming). Treatment is commonly started before administration of antiemetic agents or chemotherapy. Both acupuncture and electroacupuncture are being used (7).

Cancer Pain

Neuropathic pain

Clinical evidence for the efficacy of acupuncture in treating cancer-related pain has not been fully established. Recent data suggest a role for auricular acupuncture in patients experiencing ongoing cancer-related neuropathic pain managed with stable analgesic regimens (8).

Metastatic bone pain

A role for acupuncture in the treatment of metastatic bone pain has not been established.

Palliative pain management

Several case reports and published articles suggest a role for acupuncture in the palliation of chronic pain. Provided that caveats for the treatment, as listed in the subsequent text, are considered, acupuncture may be a helpful adjunct if performed by a trained specialist with experience in this clinical setting.

Cognitive–Behavioral Interventions

Cognitive–behavioral interventions are defined as mind–body approaches that aim to change specific thoughts and/or behaviors or to develop new coping skills (9).

Cognitive–behavioral modalities include:

  • Progressive muscle relaxation training
  • Hypnotherapy
  • Systematic desensitization
  • Biofeedback
  • Behavior modification

Summary

Behavioral interventions, including guided imagery, hypnosis, relaxation training, and emotive imagery, have been effective in (9,10):

  • Diminishing anticipatory nausea and vomiting in both children and adults with cancer who receive chemotherapy
  • Lessening anxiety and distress caused by invasive medical procedures
  • Decreasing acute pain caused by invasive medical procedures

However, there have been no documented effects of behavioral interventions:

  • in moderating chronic pain in cancer populations
  • in relieving postchemotherapy nausea and vomiting, and chronic pain.

Meditation

Cancer therapists and patients with cancer have been employing a wide range of meditation methods to alleviate cancer symptoms. The two most widely studied techniques are

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transcendental meditation (TM) and mindfulness-based meditation. TM uses the repetition of a specific mantra with the intent of quieting and ultimately “transcending” the practitioner's internal mental dialogue. Mindfulness-based meditation strives to develop an objective “observer role” for the practitioner toward his own emotions, feelings, perceptions, and so on, thereby creating a nonjudgmental “mindful” state of conscious awareness. Other meditation practices are usually pursued in a religious or spiritual context.

Transcendental Meditation

Studies of TM in patients with cancer the management of cancer symptoms are lacking. There is weak evidence that TM may help with reduction of anxiety and stress (11), but it remains unclear how this information can be translated into the cancer setting.

Mindfulness Meditation

The mindfulness-based stress reduction (MBSR) program was developed by Jon Kabat-Zinn. The components of sitting meditation, body scan, and mindful movement are taught over a training period of 7 to 8 weeks (12).

Studies of MBSR in cancer populations (13,14,15) suggest that MBSR may result in:

  • Decrease in anxiety and in mood disturbances
  • Decrease in depression, anger, and confusion
  • Change in posttreatment total stress scores

The Mindfulness-based Stress Reduction Caveats

  • MBSR is a highly structured, didactic program
  • It may not be appropriate for patients of all educational levels

Yoga

Deriving from the Ayurvedic medical system, yoga combines breath awareness and control with meditation, movement, and chanting. Studies have supported its beneficial role in stress management, anxiety reduction, and insomnia (16). Although no studies could be found that specifically utilized yoga alone as an intervention for individuals with cancer, it is likely a safe modality except in patients with bone metastases, who are at risk for pathologic fractures.

Therapeutic Massage

Therapeutic massage is generally practiced as a series of strokes and kneading movements aimed at treating the body without adjusting any body structures. Details of the array of massage techniques and approaches can be found in the literature. In general, patients should be treated only by experienced, trained, and (if applicable) licensed massage therapists.

  • The limited data available suggest that massage therapy may reduce anxiety (17).
  • No data are available on the efficacy of massage for cancer pain (17).
  • The efficacy of manual lymph drainage is unclear (18,19).

Adverse events:

  • Bruising
  • Internal bleeding
  • Fractures at sites of bone metastasis

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Caveats:

  • Coagulopathy
  • Thrombus in area of massage
  • Prosthetic devices/stents in the massage field
  • Irradiated skin and tissues

Distant Healing Modalities

“Distant healing” interventions include such modalities as therapeutic touch, Reiki, spiritual healing, prayer, and external Qigong. Some of these interventions, such as Reiki, are based on the belief that the practitioner serves as a conduit of subtle vibrational energy flow by placement of hands on the recipient, while others, such as therapeutic touch, do not necessarily require direct contact with the recipient.

  • The data claiming efficacy for these modalities is controversial from a scientific viewpoint.
  • The mechanism by which potential benefit can be derived from these modalities has not been elucidated.
  • A number of randomized clinical trials (RCTs) and several reviews of beneficial effects have been published.
  • However, only a few studies have been conducted in cancer populations.

Available data from a recent meta-analysis conducted by Astin et al. (20) show:

  • Sixteen double-blind studies of the total of 23
  • Ten positive studies using therapeutic touch versus a sham control
  • Two positive studies using distant intercessory prayer
  • Four positive studies using other forms of distant healing
  • Only one of the studies included in this meta-analysis was conducted in a population of patients with cancer (18 children with leukemia) (21).

The only RCT utilizing Reiki as an intervention in a cohort of patients with cancer (22) reported no sustained reduction in pain scores.

Complementary and Alternative Medicine for Menopausal Symptoms in Patients with Cancer

A number of botanical products including soy and soy extracts, black cohosh (Cimicifuga racemosa), chaste tree berry (Vitex agnus-cactus), don quai (Angelica sinensis), ginseng (Panax ginseng), evening primrose oil (Oenothera biennis), red clover (Trifolium pratense), motherwort (Leonurus cardiaca), and licorice (Glycyrrhiza glabra) have been widely used as adjunct treatments for menopausal symptoms including hot flashes, considered to be mostly due to the effects of the isoflavone components.

A recent review of 29 RCTs of CAM therapies for menopausal symptoms (23) concluded that:

  • Black cohosh and phytoestrogen-containing foods show promise in the treatment of menopausal symptoms
  • Clinical trials do not support the use of other herbs or CAM therapies for menopausal symptoms.

Limited data based on two RCTs of soy beverage (24) and phytoestrogen tablets (25) specifically used by postmenopausal women with breast cancer concluded, respectively, that:

  • Soy phytoestrogens administered as a soy beverage do not alleviate hot flashes
  • Pure isoflavones administered as tablets do not alleviate menopausal symptoms.

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Diet/Nutrition/Supplements

Dietary Supplements

The antioxidant vitamins A, C, and E are commonly used by patients with cancer in an attempt to improve disease outcome. There is currently no published information based on controlled clinical trials available that would suggest that a specific dietary supplement or a supplement combination is effective in curing cancer.

Vitamin A

Vitamin A may promote the progression of latent prostate cancer (26) and may result in increased lung cancer incidence in high-risk populations (27). On the basis of available evidence, vitamin A should not be administered in excess of the recommended daily allowance.

Adverse effects:

  • Hypervitaminosis A when administered in high doses

Caveats:

  • Prostate cancer
  • Lung cancer risk or lung cancer

Vitamin C

Vitamin C is an essential nutrient. RCTs with oral vitamin C have failed to show clinical benefit in the treatment of cancer (28). Some of the observed anecdotal benefits of vitamin C may be related to the much higher bioavailability of vitamin C when administered intravenously than when administered orally (29,30). There is no scientific rationale for administering vitamin C orally in high doses.

Vitamin E

Vitamin E, in addition to acting as a free radical scavenger, may block gastric formation of carcinogenic nitrosamines and may enhance the immune function. Nonetheless, clinical trials and surveys that have attempted to demonstrate a relation between vitamin E and the incidence of cancer have been generally inconclusive. Vitamin E may prevent progression of latent prostate cancer (17). Increased vitamin E serum levels following dietary supplementation have been associated with decreased risk for esophageal and gastric cancer in high-risk populations (31,32). Vitamin E in high doses interferes with platelet function (26).

Adverse effects (high doses of vitamin E):

  • Thrombocytopenia

Caveats:

  • Surgery
  • Anticoagulant therapy

Diet

Soy

Soy, a subtropical plant native to southeastern Asia, has been a main dietary component in Asian countries for at least 5,000 years. More easily digestible fermented forms of soy include tempeh, miso, and tamari soy sauce. Soy and the soy components, isoflavones (such

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as genistein), are believed to exert estrogenic effects (33,34). Although genistein has demonstrated anticancer effects in preclinical studies, the effects of genistein on cancer in humans in vivo have not been adequately determined (35). Preliminary research on humans suggests that soy isoflavones do not exert the same effects on the body as do estrogens (e.g., promoting the thickening of the endometrium) (33). It remains to be determined whether the consumption of soy by adults affects the risk of developing breast cancer, and whether soy consumption affects the survival of patients with breast cancer (36).

The role of soy and soy components in the prevention and treatment of prostate cancer in humans remains unclear (37,38).

Diet Composition

Whole grains/fiber (39)

  • Whole grains and fiber are protective against cancer, especially gastrointestinal cancers such as gastric and colonic, and hormone-dependent cancers including cancers of breast and prostate.

Fruits and vegetables

Published case–control and cohort studies are inconclusive about the protective effect of fruits and vegetables against cancer risk (40).

  • Balanced diets rich in fresh fruits and vegetables can be recommended for patients with cancer (41).
  • Extremes in diet may be associated with poorer survival rates (42).
  • Ongoing research is investigating the benefit of a diet rich in fruits and vegetables for improving survival in cancer (e.g., in breast cancer) (43,44).

Nutrition: Specialized Diets

Specialized diets have not been shown to improve cancer survival or cancer-related symptoms in controlled clinical trials, and may even be unsafe for use in some patients with cancer.

Gerson Diet

The Gerson diet is a metabolic treatment method based on the idea of detoxifying the body by eliminating commercially farmed fruits, vegetables, and prepared foods. The intake of numerous food items is restricted. The diet calls for 13 hourly glasses of juice from organically grown fruits and vegetables, supplemented by a specific regimen of supplements and coffee enemas (45). No prospective, controlled studies have been published that confirm the safety or effectiveness of the Gerson diet in the treatment of cancer.

Adverse effects:

  • Pain, diarrhea, and cramping caused by the diet itself and from the coffee enemas
  • Electrolyte imbalances
  • Infections
  • Colitis

Caveats:

This is a very stringent and restrictive regimen that may require close monitoring for risks of side effects and complications.

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Macrobiotics

Macrobiotic diets are among the most popular comprehensive, nutrition-based CAM treatment approaches to cancer. Macrobiotics is based on a predominantly vegetarian, whole-foods diet consisting of 20% to 30% vegetables, 50% to 60% cereal grains, and 5% to 10% beans and legumes. Sweets, fruits, seafood, and nuts or seeds are limited to a few times per week, whereas meats, eggs, and dairy products are consumed only once a week, if at all.

  • The dietary components of the macrobiotic diet have been associated with decreased cancer risk.
  • Macrobiotic diets may lower the levels of circulating estrogen in women.
  • The role of macrobiotics in the treatment of cancer has not been investigated adequately (46).

Adverse effects:

  • The risk of nutritional deficiencies in poorly nourished patients
  • Some components of the macrobiotic diet may alter the metabolism of certain drugs

Caveats:

  • Caution is called for, especially in women with estrogen-receptor (ER) positive breast cancer or endometrial cancer, because of the high phytoestrogen content of some macrobiotic diets.
  • Macrobiotic diets are a potentially useful adjunct to conventional treatment in well-nourished patients, if closely monitored by an experienced oncologist (17).

Gonzalez Regimen

Dr. Gonzalez's summary of the findings of Dr. William Donald Kelley, a Texas dentist, who for 20 years had been treating patients with cancer with a complicated nutritional therapy, suggested a marked survival advantage for patients with advanced pancreatic cancer, among other disease groups. An NCI-sponsored pilot study of 11 patients with advanced pancreatic cancer treated with this approach (regimen details: http://www.dr-gonzalez.com/regimen.htm) showed promising results (47). An NCI-sponsored clinical trial is actively enrolling patients with advanced pancreatic cancer (http://www.cancer.gov/ClinicalTrials/view_clinicaltrials.aspx?cdrid=67012&protocolnum=&version=patient&protocolsearchid=432236).

At this point, no published prospective clinical trials have demonstrated the efficacy of the Gonzalez regimen in the treatment of cancer.

Adverse effects:

  • Diarrhea and cramping from engaging in a regimen that includes coffee enemas
  • Electrolyte imbalances

Caveats:

  • Infectious risk associated with the ingestion of raw meat extracts

Weight Management

  • Current evidence suggests an increased risk for disease recurrence in women with breast cancer who are overweight (48,43).

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  • Research is ongoing into the role of exercise and weight management in the prevention of breast cancer recurrence (41).
  • Weight control and moderate exercise may reduce the risk for concomitant illnesses (e.g., cardiovascular disease).

COMPLEMENTARY AND ALTERNATIVE MEDICINE IN CANCER: INTERACTIONS AND CAVEATS

Botanical–Drug Interactions

The role of biologics in the CAM treatment of cancer is not discussed in detail in this chapter. However, the interaction of botanicals and nutritional supplements with pharmaceutical drugs is being reported with increasing frequency nowadays (49). Commonly used botanicals that affect the metabolism of pharmaceutical drugs in humans are listed in Table 44.1.

TABLE 44.1. Drug Interactions of Five of the Top-selling Botanicals on the U.S. Market

Botanical

Drug interactions

NNRTIs, nonnucleoside reverse transcriptase inhibitors; MAOI, monoamine oxidase inhibitors; CNS, central nervous system.
From Jellin JM, Gregory PJ, Batz F, Hitchens K, et al. “Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive Database,” Stockton CA; Therapeutic Research Faculty;http://www.naturaldatabase.com accessed on 12-05-03, with permission.

Saint John's wort

5-HT1 agonists (triptans), alprazolam, aminolevulinic acid, amitriptyline, analgesics with serotonergic activity, antidepressants, barbiturates, cyclosporine, digoxin, dextromethorphan, fenfluramine, fexofenadine, irinotecan, monoamine oxidase inhibitors, narcotics, nefazodone, NNRTIs, nortriptyline, oral contraceptives, paroxetine, phenobarbital, phenprocoumon, phenytoin, photosensitizing drugs, protease inhibitors, reserpine, sertraline, simvastatin, tacrolimus, theophylline, warfarin

                       

Ginkgo biloba

Anticoagulant-antiplatelet drugs (aspirin, heparin, indomethacin), buspirone, fluoxetine, insulin, MAOIs, seizure-threshold–lowering drugs, thiazide diuretics, trazodone, warfarin, other drugs metabolized by cytochrome P-450: CYP1A2 (acetaminophen, diazepam, estradiol, ondansetron, propranolol, and warfarin), CYP2D6 (amitriptyline, codeine, fentanyl, fluoxetine, meperidine, methadone, ondansetron, and others) and CYP3A4 [chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, and vindesine), antifungals (ketoconazole and itraconazole), glucocorticoids, fentanyl, calcium channel blockers (diltiazem, nicardipine, and verapamil), and others]

                       

Panax Ginseng

Anticoagulant-antiplatelet drugs (aspirin, heparin, indomethacin), antipsychotic drugs, caffeine, furosemide, immunosuppressants (azathioprine, cyclosporine, tacrolimus, prednisone, others), insulin, MAOIs, oral hypoglycemic agents (glimepiride, glyburide), stimulant drugs, warfarin, other drugs metabolized by cytochrome p450 CYP2D6 enzyme (amitriptyline, codeine, fentanyl, fluoxetine, meperidine, methadone, ondansetron, and others)

                       

Allium sativum (garlic)

Anticoagulant–antiplatelet drugs (warfarin, aspirin, heparin, and indomethacin), cyclosporine, NNRTIs, saquinavir (potentially, other protease inhibitors), oral contraceptives, other drugs: preparations containing allicin may increase the activity of the cytochrome P450 CYP3A4. Drugs that might be affected include chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, and vindesine), antifungals (ketoconazole and itraconazole), glucocorticoids, fentanyl, calcium channel blockers (diltiazem, nicardipine, and verapamil), and others

                       

Piper methysticum (kava)

Alcohol, alprazolam, CNS depressants, hepatotoxic drugs (azathioprine, methotrexate, and tamoxifen), levodopa, other drugs metabolized by cytochrome p450 enzymes: CYP1A2, CYP2C9 (tamoxifen and warfarin); CYP 2C19 (cyclophosphamide), CYP2D6 (codeine, ondansetron, and paroxetine), and CYP3A4 (cyclosporine and others)

                       

Caveats Related to the Use of Complementary and Alternative Medicine Therapy

A number of caveats relating to the use of CAM therapies have been listed during the course of this chapter. The following is a summary of some important caveats for consideration when using complementary therapies in the treatment of cancer patients:

Therapy

Caveat

Highly restrictive diets

Poor nutritional status

Antioxidants

Concurrent radio/chemotherapy

Supplements with anticoagulant activity

Low platelet count, surgery

Phytoestrogens

Breast cancer (ER+)

Acupuncture

Low platelet count, anticoagulation

Deep tissue/forceful massage

Low platelet count, anticoagulation

St. John's wort

Chemotherapy

High-dose vitamin A

Try to avoid

High-dose vitamin C

Try to avoid

COMPLEMENTARY AND ALTERNATIVE MEDICINE IN CANCER: INFORMATION RESOURCES

National Center for Complementary and Alternative Medicine (NCCAM)

http://www.nccam.nih.gov

Information about CAM

http://www.nccam.nih.gov/health

Information about CAM cancer research

http://www.nccam.nih.gov/research

National Cancer Institute (NCI)

http://www.cancer.gov

Information about CAM cancer research trials

http://www.nci.nih.gov/clinicaltrials

Information about CAM in Cancer

http://www.cancer.gov/cancerinfo/pdq/cam

Office of Cancer Complementary and Alternative Medicine (OCCAM), NCI

http://www.cancer.gov/occam

Information about CAM cancer research

http://www3.cancer.gov/occam/research

Office of Dietary Supplements (ODS), NIH

http://www.dietary-supplements.info.nih.gov

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Information about dietary supplements

http://www.dietary-supplements.info.nih.gov/health.aspx

Information about dietary supplement research

http://www.dietary-supplements.info.nih.gov/research.aspx

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