W Preconference - Charlotte Gyllenhaal

7/31/2019 W Preconference - Charlotte Gyllenhaal

1/18

Integrative Oncology 101:

Treatment Toxicities and Use ofSupplements

Charlotte Gyllenhaal, PhD

Block Center for Integrative CancerTreatment

Skokie, Illinois

Disclosures: Salary from Block Center for Integrative Cancer Treatment;

Managing Editor of Integrative Cancer Therapies;Grant support From Lighting Innovations, LLC


2/18

Coupler Role of Nutrients & Herbs in Rx

Supplement coupled to treatment

Matching to the Cancer Challenges:

Marshal a cancer fighting biology

Combat side effects and resistance

Enhance treatment

Counter life-threatening complications

Improve quality of life Block Center for Integrative Cancer Treatment
http://www.comstock.com/web/search/loupe.asp?Image=KS15440.JPG&Type=RF&CatID=&LightboxID=&NoPopUP=T


3/18

Major Harmful Drug Interactions

St Johns wort Strongly activates cytochrome P450

drug metabolizing enzymes and can reduce blood

levels (e.g. irinotecan).

Anticoagulants Numerous anticoagulant herbsand supplements, should be avoided in large doses

when platelet levels are low and before surgery.

Folic acid and methotrexate Anti-folate drug. CNS-active herbs and anesthesia Stimulants and

sedatives should be omitted before surgery.

Block Center for Integrative Cancer Treatment


4/18

Nausea/Vomiting

Major chemo drugs causing n/v:

Cisplatin, cyclophosphamide, doxorubicin,

etoposide, ifosfamide, temozolomide, etc.

Patients most susceptible to n/v:

Women, < 50 y/o, previous n/v, high anxiety,

morning sickness, little alcohol consumption,

expectation.



5/18

Ginger

Ginger, botanical

supplement

Blinding its taste can be a

problem in clinical trials.

Ghayur, Dig Dis Sci 2005; 50:1889-97

Pertz, Planta Med 2011; 77:973-8Shalansky, Pharmacotherapy 2007; 27:1237-47

Traditionally used for nausea

(motion sickness, morning sickness).Several studies, with somewhat

mixed results.

Mechanism: stimulate gastric

motility. May also weakly inhibit 5-HT3 receptors, cf conventional

antiemetics.

Some anticoagulant effect; patients

on warfarin reported elevated INRsand bleeding with ginger in a

longitudinal study.



6/18

Ginger and Other Herbs

Add-on to antiemetic drugs in children effective in reducing n/v.

Large Phase III RCT showed efficacy of 0.5-1.0

g/day as add-on to antiemetic drugs. No effect in Phase II trial when given with 5HT-3

receptor inhibitor or aprepitant.

Other herbs in animal trials include:

ginseng, reishi, mint oil, Baikal skullcap

Pillai, Pediatr Blood Cancer 2011; 56:234-8;

Ryan, Supportive Care Cancer 2011; epub;

Zick, Supportive Care Cancer 2009; 17:563-72.;

Haniadka, Integr Cancer Ther 2011; epub.



7/18

Fatigue

14-96% of cancer patients are affected.

Distress and decreased ability to function due

to lack of energy.

Causes are poorly understood but include: ----- tumor,

-- tumor-related and chemo-related anemia,

-- sleep disruption,

-- medications,

-- high cytokine levels, etc.



8/18

Ginseng American ginseng,botanical

supplement

Distinguish Americanvs Korean vs other

ginseng species

Qi, Biochem Pharmacol 2010; 80:957-64

Paepetropoulos, Br J Pharmacol 2007; 152:172-4. Block Center for Integrative Cancer Treatment

Two main ginseng species, Americanand Korean (Panax quinquefolius andPanax ginseng). Effectsarefairly similar but distinguishable.

Traditionally used for recovery fromillness. Anti-fatigue and immunestimulant activities inaddition to a variety of otheractivities. Recent interest in anti-fatigue properties in cancer.

A compound in Korean ginseng bindsto estrogen receptors. Ginseng takenin excess amounts or in the eveningmay promote insomnia.

Michael J. Huft


9/18

Ginseng and Cancer Fatigue

Pilot trial of American ginseng in cancer-

related fatigue.

RCT, 290 subjects. Doses of 750 to 2000

mg/day for 8 weeks

Better vitality and acceptability of treatment

for ginseng group; no differences in toxicity.

Barton, Support Care Cancer 2010; 18:179-87.



10/18

Neuropathy

Damage to peripheral nervous system due to

chemotherapy agents

Taxanes incidence 50-70% Vinca alkaloids incidence 25%

Platinum compounds incidence 4-74%;

includes delayed development after end ofchemo.



11/18

Vitamin E Vitamin Ephytochemicalsupplement

Mixed tocopherols

and tocotrienols vsalpha-tocopherolalone

Naturally occurs as a mixture oftocopherols and tocotrienols;

found in nuts, natural oils etc.

Strong antioxidant properties.

Many studies have used onlyalpha-tocopherol in long-term

supplementation to improvehealth. Results are not alwaysencouraging. Giving onlyalpha-tocopherol decreasesother tocopherols.

Vitamin E, including mixedtocopherols, has ananticoagulant effect.

Wu, Clin Chem 2007; 53:511-9Liu, Am J Clin Nutr 2003; 77:700-6

Tocopherol

Tocotrienol

http://upload.wikimedia.org/wikipedia/commons/a/ad/Tocopherol,_alpha-.svghttp://upload.wikimedia.org/wikipedia/commons/1/19/Tocotrienols.svghttp://upload.wikimedia.org/wikipedia/commons/1/19/Tocotrienols.svghttp://upload.wikimedia.org/wikipedia/commons/a/ad/Tocopherol,_alpha-.svg


12/18

Vitamin E and Neuropathy

Study n Jadad Dose Chemo Outcome Results

Kottschade2011

207 4 300mg

Taxanes&

Platinums

Grade 2+

CTCAE

Nodifference

Pace, 2010 108,

41*

evaluable

3 400mg

Cisplatin,300

mg/m2

Sensorytesting

Significantreduction

foradequate

cisplatindoses

Vitamin E and Neuropathy: recent RCTs

No difference seen in larger study with smaller dose, no threshold, mixed

chemo drugs, less precise toxicity grading. Smaller study with more detailed

outcome measurement showed difference.

Kottschade, Suuport Care Cancer 2011, 19:1769-77

Pace, Neurology 2010; 74:762-66 Block Center for Integrative Cancer Treatment


13/18

Enhancing Treatment Effects

Boost efficacy of conventional therapy

Retard resistance to conventional therapy

Currently, many are in earlier stages of

clinical development



14/18

CurcuminCurcumin,

phytochemicalsupplement, from

turmeric

Many problems withbioavailability; novel

formulations being

investigated

Turmeric is traditionally used

against inflammation and topromote digestion in

traditional medicine of India.

Multiple anticancer targetsmake it of substantial interest

in cancer treatment and

several avenues being

explored.

Poor bioavailability leads to

high doses, e.g. 2-8 gms daily.

Aggarwal, Annu Rev Nutr 2010; 30:178-99 Block Center for Integrative Cancer Treatment
http://upload.wikimedia.org/wikipedia/commons/4/40/Curcumin.svg


15/18

Curcumin and Chemotherapy

Numerous laboratory studies indicate both

chemosensitizing and radiosensitizing properties

as well as protective properties for normal cells.

Phase I-II study of curcumin with gemcitabine:21 gemcitabine-resistant patients received 8 g

curcumin with gemcitabine; median survival 4 m

after start; 19% 1-year survival.

Feasible for further study (a similar study found 8-

g dose not tolerated).

Goel, Nutr Cancer 2010; 62:919-30

Kanai, Cancer Chemother Pharmacol 2011; 68:157-64.

Epelbaum, Nutr Cancer 2010; 62:1137-41



16/18

Fish oil Fish oil, dietaryomega-3

supplement

Strong anti-inflammatory effectin lab studies

Omega-3 fatty acids decreasesynthesis of inflammatory

prostaglandins known to promotecancer, and also impact other

inflammation-related markers such as

NF-kappaB.

NF-kappaB is implicated in resistance

to chemotherapy, and fish oil

constituents suppress this, potentially

decreasing treatment resistance.

May also ameliorate cachexia,

enabling patients to maintain optimal

treatment for a longer period.

Anticoagulant effect due to anti-

inflammatory properties.

Eicosapentaenoic acid,

a fish oil constituent

Shaikh, Nutr Cancer 2010; 62:284-96

Cavazos, Prostate 2011; 71:1420-8

Kunnumakkara, Cancer Res 2010; 70:8695-705 Block Center for Integrative Cancer Treatment

Fi h Oil d L C
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17/18

Fish Oil and Lung Cancer:

Chemotherapy Efficacy

Variable FO SC p

Response 60% 25.8% .008Clinical benefit 80% 41.9% .04Toxicity nsSurvival 60% 38.7% .15 ns

Conclusion: Fish oil supplement improves response(tumor shrinkage) and clinical benefit inpatients receiving chemo for lung cancer.


Murphy,Cancer. 2011, doi: 10.1002/cncr.25933

RCT, n= 31 NSCLC patients in control (standard care) and 15 in fish oil group.

2.5 g daily during chemo.


18/18

Conclusion:

Numerous natural agents have the potentialto improve tolerance of chemotherapy.

Agents that may improve response or

survival also exist. Natural agents still in preclinical

investigations may add to evidence-based

couplers in the future. Attend Moderated Panel 1 tomorrow

afternoon for more information in this area!


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W Preconference - Charlotte Gyllenhaal