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
0
10
20
30
40
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)
0
2
4
6
8
10
12
Vitamin C Vitamin E Selenium beta-carotene
TRAP
Antioxidant
# o
f S
tud
ies
INCREASE
DECREASE
NO CHANGE
JCO 22:517, 2004
0
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