Kara Kelly, M.D.

Integrating Complementary Therapies in the Care of Children with Cancer: Research and Clinical Practice

What is CAM?

Group of diverse medical and health care systems, practices and products that are not presently considered to be part of conventional medicine

Complementary: Used together with conventional medicine

Alternative: Used in place of conventional medicine

Integrative: Combines mainstream medical therapies and CAM therapies for which there is some high quality scientific evidence of safety and efficacy

NCCAM Classification

Alternative medical systems (Traditional Chinese Medicine, Ayurveda, homeopathy)

Mind-body interventions (yoga, imagery, meditation, prayer)

Biological based therapies (herbs, high dose vitamins, antioxidants, mushrooms, enzymes )

Body based therapies (chiropractic or osteopathic manipulation, massage)

Energy therapies (Reiki, therapeutic touch, magnets)

nccam.nih.gov

Children with Cancer are using CAM

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10

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50

60

70

80

90

77-83 94-98 00-03

Year of Survey

%

Reasons for CAM Use

"to try everything possible” to reduce stress of illness improve quality of life symptom care management sometimes for cure

Columbia survey: Perceived effectiveness is high- 86% very or somewhat effective for intended purpose

How are Patients Using CAM?

STUDY ID# CAM Supplement Reason Physician Told 020081 Diet: Stopped Fried Foods; Build Immune system, NO Vegetables, Juicing Stop Tumor Promoter with fat Nutrients: Grape seed extract, Pycnogenol, Detoxify, Enhance immune system, CoenzymeQ10, Colloidal silver, Barley green, Wound healing, Antibiotic MVI Herbs: Garlic, Herbal Preparation with

Echinacea, Goldenseal, Licorice, Myrr, Enhance immune system, Detoxify, Marshmallow, Black Walnut, Tumeric, Build white blood cells, Antibiotic Capsicum, Germanium Supplements: Mataki mushroom, Acidophilus, Stop tumor growth, Replace good Royal bee jelly, Blue green algae bacteria in gut Mind/ Body: Prayer Healing, Strengthening

73% of children were enrolled on clinical trials for treatment of their malignancy

85% were using some form of CAM:

Herbs 25%Nutritional supplements 34%

J Pediatr Hematol Oncol 22:412,2000

Why the Controversy?

Few clinical trials of safety and efficacy, especially in children

Regulation of herbs and dietary supplements varies world wide, although most are not subject to the same regulations that apply to conventional drugs

Adverse Effects

Pharmacologic therapies: Direct effect Contamination Interactions with conventional medications

Adverse Effects

Aloe vera LaxativeEvening primrose oil,bovine colostrum

Nausea, GI discomfort

Borageseed oil Antiplatelet effectsCat’s claw HypotensionCayenne capsules Gastric irritationKava Hepatitis, cirrhosis, liver failureLobelia Nausea, vomiting, dizziness, diarrheaGlycyrrhizin (licorice root) Amenorrhea, diarrhea,

pseudohypoaldosteronismStar anise Seizures

Ephedra, ma huang,Sida cordifolia, pinellia

Hypertension, sudden death

Contamination of herbs

Lead TCM, Surma/kajal, bint al dhahab, Litargirio

Arsenic Iu Huang Chieh Tu Pien, other TCM

Mercury Watermelon frost (TCM)

Warfarin, DES PC-SPES

Eur J Pediatr 162:72, 2003

Herb-Drug Interactions:Sources of Information

Animal StudiesTheoreticalEmpiricalCase reportsClinical StudiesClinical Trials

HerbalGram 49:2000.

Fig. 1. Effect of St. John's wort on the plasma concentration of the active irinotecan metabolite SN-38 over time.

JNCI 94:1247,2002

Chemotherapy/Herb InteractionsCorticosteroid Cyclosporin

Reduced immunosuppression

Cordyceps, country mallow, ephedra, marshmallow, fish oils, garlic, grapefruit, L-arginine, red yeast

Increased immunosuppression

Licorice, alfalfa sprouts, astralagus, cat’s claw, echinacea, St John’s wort, vitamin E, zinc

Methotrexate

Increased hepatotoxicity

Black cohosh, echinacea, salicylate containing herbs: bilberry, meadow sweet, poplars, red clover, white willow, wintergreen

Oxidative Stress and Chemotherapy Drugs

High Anthracyclines

Pt-complexesAlkylating agentsEpipodophyllotoxinsCamptothecins

Purine/PyrimidineAntimetabolites

Low TaxanesVinca alkaloids

Observational Studies: The Effect of Cancer Therapy on Antioxidant Levels (n=31)

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12

Vitamin C Vitamin E Selenium beta-carotene

TRAP

Antioxidant

# o

f S

tud

ies

INCREASE

DECREASE

NO CHANGE

JCO 22:517, 2004

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1

2

3

4

Vitamin C Vitamin E Selenium beta-carotene

TRAP

Antioxidant

# o

f S

tud

ies

INCREASE

DECREASE

NO CHANGE

The Effect of Supplementation with Antioxidants in combination with Cancer Therapy on Antioxidant Levels (n=9)

JCO 22:517, 2004

Immunostimulants

Mistletoe, Asian mushrooms (maitake, reishi, shiitake, coriolus versicolor, PSK), Astralagus

Actions: Increase cytotoxic T-cells or NK cells activity, increase endogenous production of interferon, interleukins, or cytokines

Discourage in patients with: Hematologic malignancies, Stem cell transplants

Warning signs of Possible Interactions

Tolerance to conventional drug administration that is better or worse than expected: Unexpected refractoriness to

treatment Unusual toxic effects from treatment

Labriola D, Livingston R. Oncology 13:1999

Non-pharmacologic Therapies Chiropractic

cerebrovascular accidents, acute necrosis of holocord astrocytoma, vertebral artery dissection

Acupuncture cardiac tamponade, epidural abscess formation, HIV infection overall underlying adverse event rate: 0-1.1 per 10,000 treatments

Practitioner Licensure varies from state to state

Chiropractors: every state, Washington DC

Massage therapists: ~25 states TCM practitioners: ~25 states Naturopathic physicians: 12 states Homeopathic physicians: 3 states

Dermatologic Therapy 16:77,2003

Barriers to Research Difficulties in conducting studies of complex

therapeutic systems Emotional issues leading to biases in patient

recruitment Lack of standardization of herbs/dietary

supplements Difficulty in determining an adequate placebo CAM providers may have little incentive for

scientific evaluation of CAM therapies

Active Randomized Clinical Trials in Pediatric Cancer and CAM

TRAUMEEL S (Homeopathy) for prevention and treatment of Mucositis in SCT (COG)

Electroacupuncture for Chemotherapy induced Delayed Nausea/Vomiting in Pediatric Solid Tumors (NCI)

Silymarin in Maintenance therapy in Children with ALL and Abnormal LFTs (Columbia)

Aromatherapy for Reduction of Anxiety/Nausea during SCT (Columbia)

Massage Therapy and Childhood Cancer (Childrens Minneapolis)

Aromatherapy as an Intervention for Nausea and Vomiting in Children receiving Chemotherapy for Cancer (Childrens Minneapolis)

Clinical Services

Nausea/Vomiting

Herbs

Ginger, Peppermint, Fennel

Chamomile Compresses Aromatherapy

Citrus (Bergamont, Mandarin, Citrus Mixtures)

AcupressureP-6 Point (Acupressure bands)

Palliative Care

Alternative medical systems: acupuncture

Mind-body medicine: Meditation, prayer, music therapy

Body-based therapies: Massage Energy therapies: Reiki,

Therapeutic touch

Screening for child CAM use:

Do you give your child any herbal or plant products? Do you give your child any homeopathic products? Do you use any unconventional/alternative types of

care or therapies for your child? Do you use any special vitamin therapy for your

child? Do you use any unconventional treatments,

alternative types of care, or therapies for yourself to stay healthy or to manage a health problem?

J Pediatr Health Care 17:58,2003

Questions only identified 24% of parents using CAM

www.integrativetherapiesprogram.org

The Bottom Line…

Children with cancer are using CAM therapies

Physicians need to inquire about CAM use Biologically active therapies including herbs

and dietary supplements are often used Adverse effects and especially interactions

with conventional drugs are possible CAM therapies may be especially useful for

symptom management