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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
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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
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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
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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.
Block Center for Integrative Cancer Treatment
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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.
Block Center for Integrative Cancer Treatment
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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.
Block Center for Integrative Cancer Treatment
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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.
Block Center for Integrative Cancer Treatment
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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
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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.
Block Center for Integrative Cancer Treatment
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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.
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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
Block Center for Integrative Cancer Treatment
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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
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Enhancing Treatment Effects
Boost efficacy of conventional therapy
Retard resistance to conventional therapy
Currently, many are in earlier stages of
clinical development
Block Center for Integrative Cancer Treatment
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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
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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
Block Center for Integrative Cancer Treatment
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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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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.
Block Center for Integrative Cancer Treatment
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.
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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!
Block Center for Integrative Cancer Treatment