Integrating Complementary Therapies in the Care of Children

Integrating Complementary Therapies in the Care of Children with Cancer: Research and Clinical Practice Kara Kelly, M.D. 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) meditation, prayer)  Mind-body interventions (yoga, imagery,  Biological based therapies (herbs, high dose vitamins, antioxidants, mushrooms, enzymes )  Body based therapies (chiropractic or manipulation, massage) osteopathic  Energy therapies (Reiki, therapeutic touch, magnets) nccam.nih.gov Children with Cancer are using CAM 90 80 70 60 % 50 40 30 20 10 0 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 high86% very or somewhat effective for intended purpose How are Patients Using CAM? STUDY ID# 020081 CAM Supplement Diet: Stopped Fried Foods; Vegetables, Juicing Reason Physician Told NO Build Immune system, 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, Marshmallow, Black Walnut, Tumeric, Capsicum, Germanium Supplements: Mataki mushroom, Acidophilus, Royal bee jelly, Blue green algae Mind/Body: Prayer Enhance immune system, Detoxify, Build white blood cells, Antibiotic Stop tumor growth, Replace good bacteria in gut 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 Evening primrose oil, bovine colostrum Borageseed oil Cat’s claw Cayenne capsules Kava Lobelia Glycyrrhizin (licorice root) Star anise Ephedra, ma huang, Sida cordifolia, pinellia Laxative Nausea, GI discomfort Antiplatelet effects Hypotension Gastric irritation Hepatitis, cirrhosis, liver failure Nausea, vomiting, dizziness, diarrhea Amenorrhea, diarrhea, pseudohypoaldosteronism Seizures Hypertension, sudden death Contamination of herbs Lead Arsenic Mercury Warfarin, DES TCM, Surma/kajal, bint al dhahab, Litargirio Iu Huang Chieh Tu Pien, other TCM Watermelon frost (TCM) PC-SPES Eur J Pediatr 162:72, 2003 Herb-Drug Interactions: Sources of Information Animal Studies Theoretical Empirical Case reports Clinical Studies Clinical 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 Interactions Cordyceps, country Corticosteroid Reduced immunosuppression mallow, ephedra, Cyclosporin marshmallow, fish oils, garlic, grapefruit, Larginine, red yeast Licorice, alfalfa sprouts, Increased immunosuppression 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-complexes Alkylating agents Epipodophyllotoxins Camptothecins Low Purine/Pyrimidine Antimetabolites Taxanes Vinca alkaloids Observational Studies: The Effect of Cancer Therapy on Antioxidant Levels (n=31) 12 10 # of Studies 8 6 4 2 0 Vitamin C Vitamin E Selenium Antioxidant betacarotene TRAP INCREASE DECREASE NO CHANGE JCO 22:517, 2004 The Effect of Supplementation with Antioxidants in combination with Cancer Therapy on Antioxidant Levels (n=9) 4 3 INCREASE 2 1 0 Vitamin C Vitamin E Selenium Antioxidant betacarotene TRAP DECREASE NO CHANGE # of Studies 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)  Acupressure P-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? Questions only identified 24% of parents using CAM J Pediatr Health Care 17:58,2003 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