Integrative Care of Cancer Patients

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Integrative Care of

Cancer Patients

Paul Reilly, N.D., L. Ac, FABNO

253-382-6317

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What is integrative medicine?

Conventional Oncology

Naturopathic Medicine

Traditional Chinese Medicine

Mind-body medicine/native healing

(psychoneuroimmunology)

Aggressive secondary prevention

Teamwork!!!!

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Integrative Medicine vs CAM

Oncology

CAM

Patient & Family 3

Integration = Communication

• add group meeting photo

(2)

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

(3)

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

Increased risk of secondary cancers

Persistent marrow suppression/MDS

Infertility

Cardiac damage

Persistent fatigue

“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

(5)

Metronomic refs

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

Caution in Heme malignancies (melanoma?)

Caution with SSRI’s

Caution in autoimmunity

Adjust doses to tolerance

(6)

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

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)

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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)

!

EPA seems to inhibit proliferation and DHA promote apoptosis (Int. J. Ca 1998;75:699)

!

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

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

Melatonin

Vitamin D

Glutamine

Fish oil

Multivitamin

Green tea

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

(8)

MInd-Body Medicine

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

Stress shifts toward a TH2 type response

Glucocorticoids inhibit expression of cell

surface cytotoxicity receptors NKp30 &

NKp44

(Nature 2008;8:59)

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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

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Acupuncture & TCM

USES

:

• pain

• nausea

• diarrhea

• fatigue

• xerostomia

• hot flashes

• neuropathy

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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

• Identify biochemical individuality/risk factors • Overall wellness promotion & support groups

(9)

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)

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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)

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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

44 • “

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)

(12)

Immune Support

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Oncology tx, even surgery reduces immune

function

(Brit.J. Ca 2007;97:105)

Treat neutropenia with WBC factors

Don’t do elaborate immune tests during tx

Do address cortisol, stress and PNI

Do basic immune support, especially between

cycles of tx

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Astragalus membranaceus

Enhances phagocytic activity of monocytes

and macrophages

Increases NK cell activity

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)

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Mushrooms

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)

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)

Reishi (Ganoderma lucidum) (Ling Zhi)

Maitake (Grifola frondosa)

Shitake (Lentinus edodes)

Agaricus blazeii

Chaga (Inonotus obliquus)

(13)

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

Screening for patient for other cancers

Late effects of cancer tx

post treatment detox guidelines

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.

(14)

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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