Herbal Supplements in Cancer Care

Background

The use of complementary and alternative medicine (CAM) has become increasingly popular over recent years. CAM therapies may be defined as a group of medical and health care practices and products not considered part of conventional medicine.¹ Data obtained from the 2002 National Center for Health Statistics (NCHS) National Health Interview Survey (NHIS) revealed the following¹:

One third of the population in the United States uses some form of CAM therapy, and this number increases to 62% when megavitamins and prayer are added (National Center for Complementary Medicine [NCCAM], National Institutes of Health [NIH], Department of Human Services [DDHS]) (Figure 1)
Echinacea, followed by ginseng, were the top 2 natural remedies commonly used (Figure 2)
Approximately $36 to $47 billion was spent by the US public in 1997, with over $5 billion spent on out-of-pocket expenses on herbal remedies
CAM practice was highest in African Americans, women, individuals with higher education levels, persons hospitalized in the past year, and former smokers

CAM Use and Cancer

Cancer patients were found to have higher rates of CAM use in a recent survey by the NCCAM and the NCHS.² In a study conducted by the Mayo Clinic examining the use of CAM in patients enrolled in phase 1 chemotherapy trials, approximately 88% of patients reported the use of one form of CAM.³ In a European study assessing the prevalence of the use of CAM therapies by adult oncology patients, herbal remedies, including vitamins and minerals, were the most commonly used.⁴ Most recently, at the 2007 American Society of Clinical Oncology (ASCO) meeting, Deborah Barton, PhD, RN, of the Mayo Clinic, reported that American ginseng may decrease fatigue symptoms in cancer patients.⁵

It has been reported that approximately 13% to 63% of patients use herbal preparations.⁶ The use of nutritional supplements (vitamins and herbs) frequently used by patients with cancer raises many challenges for providers. These products are not regulated by the US Food and Drug Administration (FDA), and therefore, quality, safety, and efficacy data are lacking. Herbal remedies may interact with anticancer drugs, possibly increasing or decreasing their effects, causing possible toxicities. There may be altered pharmacokinetics, including absorption, distribution, metabolism, and excretion, if an herb is given with anticancer agents.⁶ Drug interactions may be related to changes in metabolism related to the altered expression or function of the cytochrome P450 (CYP) isoenzymes. In particular, the enzyme CYP3A4 is primarily responsible for the oxidation of a number of chemotherapy agents. Elevation or suppression of CYP activity may alter plasma concentrations, leading to decreased therapeutic effect or increased toxicity of agents.⁶

Several studies have reported that patients do not discuss use of CAM therapies with their physicians.^7-8 Physicians must have an open dialogue with patients regarding the use of herbal supplements, using a patient-centered approach.⁷ Crucial strategies to approaching herbal supplement use with patients should include a discussion regarding current knowledge of side effects, drug-herb interactions, and uses based on scientific evidence (Table 1).⁹ The goal of this approach is to provide information to enable the patient to make choices. Cancer patients who are considering the use of CAM therapy should be encouraged to discuss it with their health care providers. NCCAM is currently sponsoring a number of clinical trials to evaluate CAM use in cancer.¹⁰

In the United States, 36% of adults are using some form of CAM. When megavitamin therapy and prayer specifically for health reasons are included in the definition of CAM, that number rises to 62%. From National Center for Complementary and Alternative Medicine.¹

From National Center for Complementary and Alternative Medicine.¹

TABLE 1. HERBS AND SUPPLEMENTS

HERBS	DOSE (18 YEARS AND OLDER)	USES	USES BASED ON SCIENTIFIC EVIDENCE SAFETY INTERACTIONS (each site has a chart showing the grade of scientific evidence for each condition)
KAVA	300 mg kava extract daily by mouth in 3 divided doses for anxiety: typical doses range from 50-280 mg of kava lactones daily as a single bedtime dose or in divided doses	Anxiety, stress, and Parkinson’s disease	Click Here
GARLIC	4-12.3 mg garlic oil by mouth daily; 600-900 mg daily of noncoated, dehydrated garlic powder in 3 divided doses; the World Health Organization recommends 2-5 g fresh garlic, 0.4-1.2 g dried powder, 2-5 mg oil, 300-1,000 mg extract, or 2-5 mg allicin daily	High cholesterol, antifungal, antiplatelet effects, atherosclerosis, cancer, cryptococcal meningitis, familial hypercholesterolemia, heart attack prevention in patients with known heart disease, high blood pressure, peripheral vascular disease, tick repellent, upper respiratory infection, diabetes, stomach ulcers caused by Helicobacter pylori	Click Here
GINKGO	80-240 mg of a 50:1 standardized leaf extract taken daily by mouth in 2-3 divided doses. Tea (bags contain 30 mg of extract) 3-6 mL of 40 mg per mL extract daily in 3 divided doses, and “fortified” foods	Claudication, dementia, cerebral insufficiency, acute hemorrhoidal attacks, age-associated memory impairment, altitude sickness, chemotherapy side effects reduction, deafness, depression and seasonal affective disorder, gastric cancer, glaucoma, macular degeneration, memory enhancement, multiple sclerosis, premenstrual syndrome, pulmonary interstitial fibrosis, quality of life, Raynaud’s disease, retinopathy, tinnitus, sexual dysfunction, stroke, vertigo, vitiligo, cocaine dependence, mental performance, mood and cognition in postmenopausal women	Click Here
GINSENG	100- to 200-mg capsules by mouth 1-2 times per day has been used in studies for up to 12 weeks; 0.5-2 g of dry ginseng root taken daily by mouth in divided doses has also been used. Many different doses have been used. It has been suggested that persons taking ginseng should take a break for 1-2 weeks	Mental performance, type 2 diabetes, cancer prevention, chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease, exercise performance, fatigue, fistula, high blood pressure, immune system enhancement, intracranial pressure, low white blood cell counts, menopausal symptoms, methicillin-resistant Staphylococcus, multi-infarct dementia, quality of life, sense of well being, viral myocarditis	Click Here
ECHINACEA	Capsules: for treatment of upper respiratory infections, 500-1,000 mg by mouth 3-5 times daily for 5-7 days Expressed juice: 6-9 mL by mouth daily, divided into 2-3 doses, for 5-7 days Extract: 300 mg by mouth 3 times daily Tincture (1:5): 0.75-1.5 mL, gargle, then swallow 2-5 times daily for 5-7 days Tea: 2 teaspoons of powdered herb in 1cup of boiling water for 10 minutes daily for 5-7 days Skin application: 15% pressed herb (nonroot) juice has been applied to wounds	Cancer, immune system stimulation, low white blood cell counts after x-ray treatments, prevention of upper respiratory tract infections (adults and children), treatment of upper respiratory infection (adults), genital herpes, treatment of upper respiratory infections (children)	Click Here
SAW PALMETTO	Benign prostatic hypertrophy: 320 mg daily in 1-2 divided doses. Other suggested doses have been less studied	Enlarged prostate, male-pattern hair loss, underactive bladder, prostatitis/chronic pelvic pain syndrome	Click Here
ST. JOHN’S WORT (Hypericum perforatum)	0.17-2.7 mg hypericin by mouth and 900-1,800 mg St. John’s wort extract by mouth daily Skin treatment: 1.5% hyperforin applied for treatment of atopic dermatitis	Depression, anxiety, atopic dermatitis, obsessive compulsive disorder, perimenopausal symptoms, seasonal affective disorder, human immunodeficiency virus (HIV), social phobia	Click Here
BLACK COHOSH	Dried rhizome (root): 40-200 mg daily in divided doses Tablets: 20- or 40-mg Remifemin tablets 2 times daily Liquid extract: 40 drops tincture/liquid: 0.4-2 mL of a (1:10) ethanol tincture daily	Menopausal symptoms, joint pain	Click Here
CRANBERRY	For urinary tract infection: prevention, 90-480 mL (3-16 oz) cranberry cocktail twice daily, or 15-30 mL unsweetened 100% cranberry juice daily. 300 mL per day (10 oz) commercially available cranberry cocktail (Ocean Spray^®) has been used in well-designed research. Other forms include capsules, concentrate, and tinctures. Between one and six 300- to 400-mg capsules of hard gelatin concentrated cranberry juice extract, twice daily by mouth, given with water 1 hour before meals or 2 hours after meals has been used. One study suggests that 500 mL cranberry juice with 1,500 mL water was sufficient in helping prevent the formation of oxalate kidney stones	Antibacterial, antifungal, antioxidant, antiviral, B12 absorption in individuals using antacids, cancer prevention, dental plaque, kidney stones, memory improvement, stomach ulcers caused by H. pylori bacteria, reduction of odor from incontinence/bladder catheterization, urine acidification, urinary tract infection, urostomy care, chronic urinary tract infection prevention, children with neurogenic bladder, radiation therapy side effects (prostate cancer)	Click Here
VALERIAN	Studied doses of 400-900 mg of an aqueous or aqueous-ethanol extract taken 30 to 60 minutes before bed	Insomnia, anxiety disorder, sedation	Click Here
BILBERRY	Fresh berries: 55-115 g 3 times daily or 80-480 mg aqueous extract 3 times daily by mouth Dried fruit: 4-8 g by mouth with water 2 times daily. Other preparations of dried fruit has been used	Atherosclerosis, peripheral vascular disease, cataracts, chronic venous insufficiency, diabetes mellitus, diarrhea, fibrocystic breast disease, dysmenorrhea, retinopathy, peptic ulcer disease, night vision	Click Here
MILK THISTLE	Silymarin (Legalon) 230-600 mg daily divided into 2-3 doses Silipide 160-480 mg per day in silybin equivalents has been studied	Chronic hepatitis, cirrhosis, acute viral hepatitis, amanita phalloides mushroom poisoning, cancer prevention, diabetes, high cholesterol, liver damage from drugs or toxins	Click Here
EVENING PRIMROSE OIL	Eczema or atopic dermatitis: 4-8 g daily by mouth, divided into several smaller doses throughout the day Breast pain: 3 g daily by mouth, divided into several smaller doses throughout the day	Eczema, skin irritation, breast cancer, breast cysts, mastalgia, chronic fatigue syndrome, postviral infection syndrome, diabetes, diabetic neuropathy, multiple sclerosis, obesity/weight loss, pre-eclampsia, Raynaud’s phenomenon, rheumatoid arthritis, ichthyosis vulgaris, asthma, attention deficit hyperactivity disorder, cardiovascular health, menopause, premenstrual syndrome, psoriasis, schizophrenia	Click Here

Data from Medline Plus, National Library of Medicine.⁹

References

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 June 27, 2007.
National Center for Complementary and Alternative Medicine (NCCAM). Cancer and CAM. Available at: http://nccam.nih.gov/health/camcancer. Accessed June 27, 2007.
Dy GK, Bekele L, Hanson LJ, et al. Complementary and alternative medicine use by patients enrolled onto phase I clinical trials. J Clin Oncol. 2004;22:4810-4815.
Deng, G, Cassileth, B. To what extent do cancer patients use complementary and alternative medicine? Nat Clin Pract Oncol. 2005;2:496-497.
MedPage Today. ASCO: American ginseng may ease cancer-related fatigue. Available at: http://www.medpagetoday/HematologyOncology/Chemotherapy/tb/5825. Accessed June 27, 2007.*
Sparreboom A, Cox MC, Acharya MR, Figg WD. Herbal remedies in the United States: potential adverse interactions with anticancer agents. J Clin Oncol. 2004;22:2489-2503.
Frenkel M, Ben-Arye E, Baldwin CD, Sierpina V. Approach to communicating with patients about the use of nutritional supplements in cancer care. South Med J. 2005;98:289-294.
Richardson MA, Straus SE. Complementary and alternative medicine: opportunities and challenges for cancer management and research. Semin Oncol. 2002;29:531-545.
Medline Plus, National Library of Medicine, National Institutes of Health. All herbs and supplements. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/herb_All.html. Accessed June 27, 2007.
National Center for Complementary and Alternative Medicine. National Institutes of Health. All NCCAM clinical trails. Available at: http://nccam.nih.gov/clinicaltrials/alltrials.htm#c. Accessed June 27, 2007.

*Click on MedPageToday Breaking Medical News-CME; click on Meeting Coverage in the left column; click on ASCO; click back to 6/02/07 News Brief.

Key Definitions

complementary medicine—used together with conventional medicine; alternative medicine—used in place of conventional medicine. When CAM is used in combination with conventional medicine it is termed integrative medicine.

efficacy—effectiveness or ability of a drug to control or cure an illness: the maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it was prescribed. In the procedure mandated by the FDA, phase 2 clinical trials gauge efficacy and phase 3 trials confirm it.

pharmacokinetics—tof or relating to the study of the bodily absorption, distribution, metabolism, and excretion of drugs. It is often summarily stated that pharmacokinetics is the study of what the body does to the drug.

cytochrome P450—human cytochrome P450, also known as CYP and primarily found in the cells of the liver and small intestines; understanding the reactions of a drug depends on knowing the role of CYP.

CYP34A—specific genetic code of the P450 superfamily. Of all the CYPs in the liver, 34A is in the largest quantity; in the intestine, it plays an important role in the metabolism of certain drugs.

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