Integrative Care of
Cancer Patients
Paul Reilly, N.D., L. Ac, FABNO
253-382-6317
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What is integrative medicine?
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Conventional Oncology
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Naturopathic Medicine
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Traditional Chinese Medicine
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Mind-body medicine/native healing
(psychoneuroimmunology)
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Aggressive secondary prevention
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Teamwork!!!!
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Integrative Medicine vs CAM
Oncology
CAM
Patient & Family 3Integration = Communication
• add group meeting photo
Why do we need integrative medicine?
• 83% of pts surveyed already used at least 1 CAM therapy (68.7% excluding spiritual practices)
– (JCO 2000;18:2505)
• 65% of oncology pts used supplements. Up to 95% used some sort of CAM for support
– (J Alt Comp Med Sept 2002)
• 66.7% of breast cancer pts reported using CAM. Only 50% of those told their doctor.
– (JCO 2000;18:2515)
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•Side effects limit dosage
•Limited efficacy
•Secondary cancers & late effects
•Expense to patient and society
“unsustainable”
(Lancet Oncology 9/26/11 , American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. Presented May 31, 2015.)Why do we need integrative medicine?
Problems of conventional treatments
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Why do we need integrative medicine?
• Use of CAM is not associated with poor
compliance with conventional tx, but with
active coping behavior
(Cancer 2000;89:873)• IM can improve tolerance of treatments • IM can improve patient compliance
• IM appears to improve responses to tx and survival
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Risk vs Benefit Analysis
• tx d/c for neuropathy, cardiac damage, marrow depression, severe mucositis, severe infection or chronic wasting
• secondary cancers after chemotherapy or radiation • long term myelosuppression post tx and increased
risk of lymphoma and acute leukemias 3-5 years post tx.
• increased risk of late effects from cancer tx
How do we do it at SIOCC?
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SIOCC Model of care
•Patient focused treatments
•No rigid protocols
• Personalize tx for particular cancer, stage and molecular characteristics with leading edge conventional therapies.
• Factor in lifestyle and personal preferences • Patient involved in decision making
• Provide the most effective combination integrative therapies to support the patient and the treatment
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Chemotherapy
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Types of chemotherapy- Cytotoxics
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Types of chemotherapy - Biologics
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Chemotherapy Side effects
• Acute: • Hair loss • Nausea/vomiting • Constipation/diarrhea • Mucositis • Neuropathy • Anemia/Leukopenia • “Chemo brain” • Fatigue 14 14
Long Term Side Effects
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Development of drug resistance
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Increased risk of secondary cancers
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Persistent marrow suppression/MDS
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Infertility
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Cardiac damage
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Persistent fatigue
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“Chemo brain”
(NEJM 2006;355:1572)
Reducing Side Effects with
Metronomic Chemotherapy
• Using lower doses more frequently to achieve the same or greater total dose
• more frequent dosing increasing chance of catching cells in proper phase of cell cycle
• lower dosing reduces side effects
Metronomic refs
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LDM therapy displayed a stronger
anti-tumor activity in suppressing
primary and metastatic breast
tumors with less degree of side
effects, and stronger anti-angiogenic
and anti-lymphangiogenic activities
than MTD therapy.
( Cancer Invest. 2010 Jan;28(1):74-84.)
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Co-treatment goals
•Reduce side effects of treatments
•Support tumoricidal action of treatments
•Inhibit angiogenesis
•Limit mutation to more aggressive/MDR
stages
•modify other risk factors (hormones,
inflammation, immunity etc)
•survivorship report
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Supporting Chemotherapy
•Adding 20 mg melatonin to standard therapy for stage 4 cancer doubled response to tx and doubled survival at 1 yr
•Eur. J. Ca 1999;35:1688
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Melatonin Cautions
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Caution in Heme malignancies (melanoma?)
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Caution with SSRI’s
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Caution in autoimmunity
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Adjust doses to tolerance
Supporting Chemotherapy
•Adding 20 mg melatonin to standard therapy for stage 4 cancer doubled response to tx and doubled survival at 1 yr
•Eur. J. Ca 1999;35:1688 !
•Improving vitamin D levels significantly improved outcomes and survival in lymphoma pts receiving R-CHOP chemotherapy • ASCO 2013 -post 103 21 21 22
Vitamin D
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Pretreatment with 1,25 dihydroxy vitamin D led to approx 75% enhancement of action of dox against ca cells. (Ca Res. 1999;59:862)•
Treatment of MCF-7 cells with the 1.25 dihydroxy vitamin D alone markedly reduced activity and growth rates•
Reduces osteoporosis during hormone blockade•
Enhances response to taxotere in advanced prostate cancer (ASCO 2002)22
Glutamine
• Reduces taxol induced neuropathy & myalgias ( J. Pharmacol. Exp. Ther. 1996;279:410)
• Reduces GI, neuro & cardiac complications of cancer tx ( Ca Tx Reviews 2003;29:501)
• Reduces mucositis (Cancer 1998;83:1433)
• Increases tumor retention of chemotherapy (Ann Surg 1998;227:772)
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Fish Oils & EPA
•Serve as precursors to desirable prostaglandins protecting against multiple cancers (Pharm. Ther. 1999;83:217)
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EPA seems to inhibit proliferation and DHA promote apoptosis (Int. J. Ca 1998;75:699)
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EPA and DHA act as an MMP inhibitor ( J. Nutr. Biochem 2005;16:17)
!
Enhances activity of CPT-11 and adriamycin & 5FU
(Brit J Ca. 1999;81:440)( Eur. J. Nutr 2003;42:324)
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Green tea
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Promotes caspase 3
(Biochem Biophys Res Comm 2000;270:793)•
Inhibits MDR p-glycoprotein
(Biochem et Biophys Res Acta 2002;1542:149)•
Enhances DOX antitumor activity
( Toxicology Letters 2000;114:155)•
Enhances paclitaxel activity in breast cancer
(Breast Ca Res 2010;12:epub)
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Safe basic support during
most chemotherapy
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Melatonin
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Vitamin D
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Glutamine
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Fish oil
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Multivitamin
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Green tea
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Vit. C & Immune support
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avoid during most chemotherapy
• Quercetin
• NAC
• Alpha lipoic
acid
• Milk Thistle
-St John’s Wort/hypericum
-Grapefruit juice
-Tagamet
-Most drugs/nutrients
sharing same p450 liver
pathway
Why risk it?
• Majority of pts use without guidance • Some refuse tx otherwise
• Some need early d/c or dose reductions • Long term side effects
• Secondary cancers • Lower response rates
MInd-Body Medicine
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High levels of stress impaired NK cell lysis in
breast cancer patients
(J. Surg. Res. 2007;139:36)•
Stress raises cortisol levels and reduces
immune activity
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Stress shifts toward a TH2 type response
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Glucocorticoids inhibit expression of cell
surface cytotoxicity receptors NKp30 &
NKp44
(Nature 2008;8:59)29
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Acupuncture and TCM
• based upon theory of
yin & yang and energy
flow through meridians
• treatments include
needling, herbs, moxa,
tui na (massage) and
dietary advice
30 30Acupuncture & TCM
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USES
:
• pain
• nausea
• diarrhea
• fatigue
• xerostomia
• hot flashes
• neuropathy
31Aftercare - (secondary prevention)
• Prevent return of original cancer
• Stop new occurrence of same type cancer • Prevent other types of cancer
• Prevent treatment induced cancer & other treatment induced pathology
• Identify biochemical individuality/risk factors • Overall wellness promotion & support groups
Aftercare - (secondary prevention)
• Prevent return of original cancer
• Stop new occurrence of same type cancer • Prevent other types of cancer
• Prevent treatment induced cancer & other treatment induced pathology
• Address individual health concerns
• Overall wellness promotion & support groups
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The good news
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The microenvironment surrounding a
tumor cell can promote or discourage
tumor progression independent of tumor
genetics
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(Tumor suppressor or promoter genes)!
! ! Int. J. Cancer 2003;107:688! ! JNCI 2002:941494 34 35 1/14/14, 2:11 PM Cancer-Pathways.png 720×856 pixels 36
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Insulin, obesity & cancer
• Obesity could account for 14% of all cancer
deaths in men and 20% in women
(NEJM 2003;348:17)• 60% higher risk of colon cancer with higher
levels of insulin. 90% increase with highest
waist circumference
(JNCI1999;91:1147)• Multiple factors including insulin, IGF-1,
adipokines, TNF-alpha, VEGF & sex hormones
all impact risk of cancers
(Horm Mol Biol Invest 2015;21:5)37
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Inflammation & cancer
Chronic inflammation can contribute to cancer!
Carcinogenesis 2010;31:37
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Herbal anti-inflammatories
Suppression of NF-KB increases apoptosis and improves responses to some chemotherapy!
Cell Death and Differentiation (2006) 13, 738–747.!
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Natural NF-KB Inhibitors: !
silymarin, melatonin, resveratrol, vitamin D, GLA, vitamin C, ginger, GSH, curcumin, alpha lipoic acid, ashwaganda, gugulipid, rosemary, I3C! Mol Ca Ther 2006;5:1434! J. Biol. Chem 2004;279:47148! J. Surg. Res. 2007;142:281! Blood 2005 39
Vitamin D
• Reduces cancer rates at 16 sites (Antica. Res. 2006;26:2687)
• Low vit D assoc with increased cancer incidence & mortality ( JNCI 2006) (Am. J. Pub. Health 2006) • Increasing vit D by 25 nml/l assoc with 17%
reduction in ca incidence, 29% reduction in ca mortality and 45%reduction in dig system ca mortality (JNCI 2006;98:451)
Serum Vit D & breast cancer risk
serum vit D (nm) RR for breast ca
<30 1 30-45 0.57 45-60 0.49 60-75 0.43 >75 0.31 Carcinogenesis 2008;29:93 41 41
Another Way of Thinking
• Must we kill to cure?
● Schipper et al J. Clinical Oncology 1995;13:801!
• Cancer is a defect in regulation, not an external invasion
• Cancer cells are mostly normal
• The imbalance is potentially reversible • Using killing strategies alone may be
counterproductive
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Another Way of Thinking
• Host response is critical
• Cancer growth rates are variable, depending on the regulatory balance
• functional cure does not require a complete response
• Complete response may not be the best predictor of long term survival
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Another Way of Thinking
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Rather than trying to cure cancer by
killing off every last cell, it would make
more sense to control the disease and
extend latent disease-free periods by
enhancing or encouraging the factors
which maintain that state of dynamic
equilibrium where progression is
self-limiting”
(Lancet 1996;348:1149)Immune Support
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Oncology tx, even surgery reduces immune
function
(Brit.J. Ca 2007;97:105)•
Treat neutropenia with WBC factors
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Don’t do elaborate immune tests during tx
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Do address cortisol, stress and PNI
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Do basic immune support, especially between
cycles of tx
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Astragalus membranaceus
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Enhances phagocytic activity of monocytes
and macrophages
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Increases NK cell activity
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Increases T cell activity and corrects T cell
dysfunction in sera of cancer pts
(J. Clin. Lab Immunol 1988;25:119)•
Activates cytotoxic activity and cytokine
production ( IL-2 and IFN-gama)
(Ca Invest 1999;17:30)46
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Mushrooms
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Mushrooms do not exert direct antitumor
effects but act through the immune system
which requires a functional T cell component
(Appl Microbiol Biotechnol 2002;60:258) (Anticancer res 2000;20:4707)
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NK activity & quality of life improved in gyn
oncology pts undergoing chemotherapy
(Int J. Gyn Ca 2004;14:589)•
Ganoderma lucidum suppresses growth of
breast cancer cells by inhibition of NF-KB
(Nutr Cancer 2004;49:209)
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PSK (Coriolus versicolor)
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Reishi (Ganoderma lucidum) (Ling Zhi)
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Maitake (Grifola frondosa)
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Shitake (Lentinus edodes)
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Agaricus blazeii
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Chaga (Inonotus obliquus)
The take home message…
• Change the internal
environment that
supports cancer
growth, and you change
the outcome.
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Putting it all together
• Healthy Diet
• Don’t smoke
• Alcohol in moderation, (if any)
• Stay Active
• Maintain Healthy weight
• Take time for fun
• Sleep
• Take high quality vitamins
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Other Considerations
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Screening for patient for other cancers
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Late effects of cancer tx
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post treatment detox guidelines
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Family member risk
Summary
• The future of oncology lies in wise use of
appropriately selected, less toxic, more
tumor-specific targeted conventional
therapies, along with patient-specific,
tumor-specific, and treatment-specific
integrative therapies.
Summary
• Conventional cancer therapies cure only
50% of patients and entail many short term
and long term side effects
• Integrative medicine has been shown to
reduce side effects while enhancing
response to conventional therapies
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Summary
• Cancer is a systemic and cellular
problem. If we neglect the issues
that permitted it to grow initially it
is much more difficult to treat,
(and more likely to recur after
treatment.
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