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Complementary, Alternative, and Integrative Medicine:Epidemiology and Relevance to Oncology

Dr. Ather Ali, ND, MPH, MHS (c)Associate Research Scientist, Department of PediatricsIntegrative Medicine Specialist, Yale Stress CenterDirector, Integrative Medicine at Yale

Atatürk ÜniversitesiMay 2014

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Outline

• Reasons for seeking CAM/IM• Risks of CAM therapies in oncology• Research in CAM therapies• Safety / efficacy balance• Treatment guidelines• Information Resources

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Motivations for seeking CAM

• Same as other reasons for CAM/Integrative Medicine– Personal values– Sense of empowerment / participation in self-care– Concern about safety of conventional medicine– No resolution or improvement with conventional treatment– Desire for a “holistic” approach

• Cancer patients use CAM to – reduce adverse effects/organ toxicity– improve quality of life– protect and stimulate immunity– reduce risk of further cancers

• In most cases, patients are not disappointed/dissatisfied with conventional medicine

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Cancer – CAM epidemiology in the United States

• 7-64% of cancer patients use some type of CAM (1)– Mean of 32%

• 68% of radiation therapy patients (2)– Majority are female and college-educated. – Of these, 58% discussed use with their physician

• 80% of breast cancer patients reported use of CAM (3)– Of these, 41% specifically to treat the cancer

1. Cancer. 1998 Aug 15;83(4):777-82. Review.2. Am J Clin Oncol. 2006 Oct;29(5):468-73.3. BMC Womens Health. 2007 Mar 30;7:4.

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Cancer – CAM epidemiology

• CAM use increases after diagnosis• High-risk women attending a genetic testing program

were found to be using CAM at rates (53%) comparable to those reported in active treatment – especially in BRCA-1 + patients

• Radiation therapy– High rates (68%); especially dietary supplements (80%)

• Use of CAM often continues long after completion of conventional care

• Majority (53%) of patients using dietary supplements during recent chemotherapy did not seek advice from a medical provider

Hematol Oncol Clin North Am. 2008 Aug;22(4):581-617.

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Cancer – CAM risks

• When used as as a substitute for conventional treatment in 33 women with breast cancer– early death, higher rates of recurrence

• Every ‘‘natural cancer cure’’ examined so far has failed rigorous clinical trials– shark cartilage - no benefit– laetrile - ineffective and toxic (cyanide poisoning)

• Even for patients with advanced disease, most (88%) receive CAM care concurrently with conventional care– minority (8% in one study) who choose solely alternative

cancer care

Hematol Oncol Clin North Am. 2008 Aug;22(4):581-617.

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Cancer – CAM risks (2)

• PC-SPES removed from the market in 2002– found to contain warfarin, diethylstilbestrol, and other

substances • U.S. FDA – new rules regarding dietary supplement

quality– DSHEA – Dietary Supplement Heatlh and Education Act

(1994)– Current Good Manufacturing Practices– Structure/Function claims

• Hepatotoxictiy with some herbs– chaparral (Larrea tridentate), comfrey (Symphytum

officinale), and kava (Piper methysticum)

Hematol Oncol Clin North Am. 2008 Aug;22(4):581-617.

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Natural product-Drug Interactions?

• 4% chemotherapy patients surveyed were using herbs (St. John’s wort and garlic) that may affect chemotherapy metabolism.

• In 318 chemotherapy patients using herbal remedies– 11% took supplements in higher than recommended doses– potential interactions identified in 12%

• Herb with strongest risk of clinically significant interactions is St. John’s wort (Hypericum perforatum)– Can inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and

CYP3A4

Hematol Oncol Clin North Am. 2008 Aug;22(4):581-617.

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Antioxidants?

• Potential for interactions and reduced efficacy• Most concerns are theoretical

– limited evidence for harm– mainly for vitamin E with head and neck cancer patients

• large amounts of pre-clinical data and limited human data to support antioxidant use– (intravenous / high-dose) Vitamin C – tumor response?– IMC experience and thought process– CoQ10 and vitamin E for doxirubicin-related cardiotoxicity

Hematol Oncol Clin North Am. 2008 Aug;22(4):581-617.

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Contemp Pediatr 2004;21:61-72.

How to navigate inconclusive evidence

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Promising Research - 1

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Promising Research - 2

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Promising Research - 3

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Promising Research - 4

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Society for Integrative Oncology Guidelines - Acupuncture

• Recommended for:– Poorly controlled pain– Clinically significant side effects such as neuropathy or

xerostomia– Nausea/vomiting due to chemotherapy– Smoking cessation– Dsypnea, fatigue, chemotherapy induced neuropathy, or post-

thoracotomy pain– Caution with patients with bleeding tendencies

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Radiation and CAM - benefits

• Relaxation therapies–tension, depression, anger, fatigue (1)

• Acupuncture–xerostomia; can last up to 3 years (2)

• Acupuncture–fatigue (2)

• Probiotics–diarrhea (3)

• Glutamine–Decreased rates and severity of mucositis, neuropathy, and intestinal toxicity; decreased use of pain meds in stomatitis patients; improved nutrition in stomatitis patients; improved ADL in neuropathy patients

• Vitamin E / Zinc / Chamomile–improved stomatitis

• Calendula lotion–helpful for dermatitis

• Pomegranate juice–increased PSA doubling time1. J Clin Psychol 1992;48:388–932. Journal of the Society for Integrative Oncology, Vol 5, No 2 (Spring), 2007: pp 65–843. Hematol Oncol Clin North Am. 2008 Aug;22(4):581-617, vii. Review.

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Radiation and CAM - harms

• RCT of 540 patients with head and neck cancer undergoing radiation (1)– Subjects given antioxidants (400-IU α-tocopherol, 30-mg β-

carotene) or placebo daily throughout radiation therapy and for 3 years afterwards.

• Acute side effects of radiation were significantly less in the antioxidant group

• Local recurrence higher in antioxidant group (OR 1.37; CI 0.93–2.02). – After a median follow-up of 6.5 yr– all-cause mortality significantly higher in antioxidant group

(HR 1.38; CI 1.03–1.85) (2)

1. J Clin Psychol 1992;48:388–932. Journal of the Society for Integrative Oncology, Vol 5, No 2 (Spring), 2007: pp 65–84

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IMC Experience: Intravenous Vitamin C

• Early clinical studies showed that high-dose vitamin C, given by intravenous and oral routes, may improve symptoms and prolong life in patients with terminal cancer.

• Double-blind RCTs of oral vitamin C therapy showed no benefit

• At concentrations above 1000 µmol/L, vitamin C is toxic to some cancer cells but not to normal cells in vitro.

• Case reports (kidney, bladder, paraspinal) are intriguing.• Patient demand vs. safety concerns (particularly renal)

• Created policy/procedure• Input from pharmacy, medical oncology, legal, and experts

in the field

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Cancer – CAM resources

• http://www.cancer.gov/CAM/• http://nccam.nih.gov/health/cancer/• Abrams D and Weil A. Integrative Oncology. Oxford

University Press, 2009.• Society for Integrative Oncology: www.integrativeonc.org• Integrative Medicine in Oncology: Hematol Oncol Clin N

Am 24 (2008)

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This work was supported by a grant from

National Center for Complementary and Alternative MedicineNational Institutes of HealthU.S. Department of Health and Human Serviceswww.nccam.nih.gov