8.5mb - Genova Diagnostics

Integrative Strategies for
Supporting Patients
Diagnosed with Breast Cancer:
Part II
Lise Alschuler, ND, FABNO
Genova Diagnostics LiveGDX
June 25, 2014
Margaret Steele, ND
Medical Education Specialist - Asheville
Lise Alschuler, ND, FABNO
http://www.drlise.net
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Integrative Co-Management for Patients Being
Treated for Breast Cancer
Lise Alschuler, ND, FABNO
June 25, 2014
6
Outline of Topics
• Conventional treatment and
integrative co-management
• Safety
• Synergistic agents
• Side-effect management
7
Breast CA: conventional Tx
• Conventional management:
– Surgery
– Chemotherapy (especially for women under age 50; even
with node-negative disease)
• Adriamycin/Cytoxan or Epirubin/Cytoxan or
Taxotere/Adriamycin/Cytoxan
• Cytoxan/Methotrexate/Fluourouracil
• Taxane (usually Taxotere)/Cytoxan [Her-2 negative]
– Radiation
– Hormonal therapy (tamoxifen, AIs)
– Trastuzumab (Herceptin) for Her2neu+
8
Effective chemotx combinations
• AC: doxorubicin & cyclophosphamide
• AC-T: doxorubicin & cyclophosphamide followed
by paclitaxel or docetaxel
• FEC: 5-FU, epirubicin & cyclophosphamide
• FEC-D: 5-FU, epirubicin & cyclophosphamide
followed by docetaxel [Canada]
• CMF: cyclophosphamide, methotrexate & 5-FU
• TC: docetaxel & cyclophosphamide
• CAF: 5-FU, doxorubicin & cyclophosphamide
• EC: epirubicin & cyclophosphamide
• TAC: docetaxel, doxorubicin & cyclophosphamide
9
Chemotherapy
• Dose-dense chemotherapy
– Cycles of chemo are given closer together: q 2 weeks
instead of every 3 weeks
– Can decrease recurrence and improve survival
– Associated with increased adverse effects
– Colony stimulating factors (Neupogen or Neulasta) to
prevent leukopenia is given after each cycle of chemo
10
Rationale for chemotherapy
• Women <50y
– 30% reduction in annual relative risk of death
– 10% absolute improvement in 15-year survival
• 42% 15-yr survival with chemo vs. 32% without chemo
• Women >50y
– 12% reduction in annual relative risk of death
– 3% absolute improvement in 15-year survival
• 50%15-yr survival with chemo vs. 47% without chemo
11
Oncotype Dx
 A 21-gene reverse transcription-PCR-based assay from tumor
tissue
 Done on node-negative, ER+ patients
 Assumes 5 years of Tamoxifen and predicts risk of recurrence
and expected benefit (or not) of chemotherapy
 MammaPrint is a 70-gene array from tumors of women with
node negative, unknown ER status
12
Oncotype
DX sample
test report
13
INTEGRATIVE THERAPIES: SAFETY
14
Evidence Table
Journal of the Society for Integrative Oncology, Vol 7, No 3 (Summer), 2009: pp 85–120
15
Potential risks of DS
 Use of DS as alternative therapies could delay curative




conventional therapy
Herb-Drug or Nutrient-Drug interactions with conventional
chemotherapy
Some dietary supplements may interfere directly with the
action of chemotherapy or radiation
Presence of toxic constituents or adulterants in poor quality
dietary supplements
Potential interference with coagulation or platelet function
16
Ex. Herb/Drug interactions
Botanical
Interaction (largely pre-clinical data)
Garlic
Avoid with decarbazine (CYP2E1 inhibition)
Ginkgo
Avoid during chemotx (CYP3A4 and CYPC19 inhibition)
Echinacea
Avoid during chemotx (CYP3A4 induction)
Hypericum
Avoid during chemotx (CYP3A4, -2B6, -2C9, -2C19, -2E1 induction and
induces p-glycoprotein expression → drug resistance). Especially avoid
with irinotecan – reduces metabolism of active metabolite (SN-38)
Valerian
Avoid with tamoxifen and cyclophosphamide (CYP2C9 and CYP2C19
inhibition)
Berberine
Avoid with taxanes (increases MDR transporter expression)
Curcumin
Caution with camptothecin, mechlorethamine, cyclophosphamide,
adriamycin, doxorubicin (interferes with apoptotic mechanisms).
Cimicifuga
Avoid with –platin chemotherapy (may decrease cytotoxicity of cisplatin)
17
Ex. Supplement/Drug interactions
Supplement
Interactions (based largely on pre-clinical data)
NAC, glutathione and alpha-lipoic
acid
Caution with –platins (Carboplatin, Cisplatin, Oxaliplatin)
and Avoid with Radiation therapy
Glucosamine
May interfere with anti-tumor actions of etoposide and
adriamycin (interferes with topoII inhibition)
Quercetin
Interferes with anti-tumor actions of cyclophosphamide
(JNK suppression) and taxanes (interferes with kinase
inhibition)
Beta-carotene and alphatocopherol
Interferes with chromosomal damage from mitomycin-C
and with radiation induced cytotoxicity – especially in
smokers
CoQ10
High doses (>300mg daily?) may interfere with radiation
induced cytotoxicity
18
Antioxidants: bottom line
 Overall, the evidence is suggestive of a beneficial effect of
antioxidant use on tolerance to chemotherapy.
 Maintenance of sufficient redox potential is necessary for
chemotherapy and radiation tumoricidal effects by
maintaining apoptosis.
 There is no clinical trial evidence of harm from, or interference
by, antioxidants during chemotherapy.
 Antioxidants (specifically alpha-tocopherol and betacarotene) appear to have deleterious effects in smokers
receiving radiation and so should be avoided in this
population.
 The use of supplemental carotenoids is associated with
increased mortality risk and should be avoided in smokers
and during active treatment
ATBC Cancer Prevention Study Group NEJM 1994 330(15):1029-35
Omens GS et al. J Natl Cancer Inst 1996 88(21): 1550-9.
19
Antioxidants and Breast CA
 Systematic review of antioxidants in breast cancer
 Twenty-two observational studies and trials
 Conclusion: Insufficient evidence to support or negate the
value of antioxidants concurrent with chemotherapy.
 However, the observational studies demonstrated
that there was reduced recurrence for patients
who used vitamins C and E and increased
recurrence for those who used combination
carotenoids.
Greenlee H. et al. Breast Cancer Res Treat. 2009 Jun;115(3):437-52
20
SYNERGISTS
(BREAST CA SPECIFIC)
IV AA
Mushrooms
DHA
21
IV Ascorbic Acid

N=125 breast cancer patients, stages IIA - IIIB




53 patients received i.v. vitamin C 7.5 g once a week
during adjuvant therapies
72 patients received SOC only
No IVC administered on the days of chemo or
radiation
Significant reduction in nausea, loss of appetite,
fatigue, depression, sleep disorders, dizziness, and
hemorrhagic diathesis
22
Vollbracht C. et al. In Vivo. 2011 Nov-Dec;25(6):983-90
Mushrooms
 PSK, extracted from Coriolus (aka Trametes)
versicolor has been assessed in over 31 Phase I-III
RCTs in over 9600 patients with gastric, colorectal,
esophageal and breast cancers.
23
Coriolus (Trametes) versicolor
[Turkey Tail]
• Systematic review and meta-analysis of 13 trials that met
inclusion criteria
• Cumulatively, there was 1,284 patients in the PSK/PSP group
(49.6%) and 1,303 in comparison groups(50.4%)
– Overall survival at 5 years was improved in the PSK/PSP group
P<0.00001; RR=1.14
• Over all cancers, there was a 9% absolute reduction in 5-year
mortality (one additional patient alive for every 11 pts treated)
• Effects were more evident for breast, gastric or colorectal cancer
versus esophageal or nasopharyngeal
LY Eliza W, K Fai C, P Chung L. Recent Patents on Inflamm & Allergy Drug Discov. 2012;6(1):78
24
5 year survival rates
P=0.006
Five-year overall survival curves for all eligible patients in the
immunochemotherapy group (solid line) and chemotherapy group (dotted line)
25
Survival odds
Survival odds ratios and their 95% CIs for each trial and overall (test for
treatment effect P=0.006)
Alschuler 2014
26
Breast Cancer: DHA and
anthracyclines
 This open-label single-arm phase II study
evaluated the safety and efficacy (response
rate) as primary end points with the addition
of 1.8 g DHA daily to an anthracycline-based
chemotherapy (FEC: fluorouracil, epirubicin,
cyclophosphamide) 3 week regimen
 Breast cancer patients (n = 25) with rapidly
progressing visceral metastases.
 The secondary end points were time to
progression (TTP) and overall survival (OS).
Bougnoux P., et al. British Journal of Cancer.2009;101:1978 – 1985
Alschuler 2014
27
Intervention
 0.5 g capsules of DHASCO containing DHA
enriched triglyceride oil of algal origin (44% DHA
providing 0.2-g DHA). [Martek Biosciences Corp.]
 Patients received nine 200mg capsules of
DHASCO daily
 DHA was administered from inclusion before
initiation of chemotherapy (a 7–10-day loading
period) and then for the 5 months of
chemotherapy (except on day of chemo.)
 Patients were explicitly asked to avoid any intake
of anti-oxidants.
Alschuler 2014
28
Results
 In terms of survival, frontline FEC chemotherapy in this
setting has been found to induce a median TTP ranging
from 6 to 13 months and a median OS ranging from 18
to 23 months
 In this study, the median TTP was 6 months and
median OS was 22 months, consistent with expected
results.
 However, median OS reached 34 months in the subpopulation of patients (n =12) with the highest plasma
DHA incorporation
 Neutropenia was the most common adverse toxicity
Alschuler 2014
29
Survival and DHA incorporation
Time to Progression
Overall Survival
Alschuler 2014
30
Mechanism of action
 This highly unsaturated fatty acid incorporates into
cell membrane phospholipids, particularly in fast
growing or proliferating cells such as tumor cells.
 DHA enhances the tumor cell chemosensitivity,
specifically to anthracyclines. This is likely the result
of anthracyclin induced peroxidation of membraneenriched DHA.
 There is increased sensitivity of fast dividing tumor
cell lines due to the lack of glutathione peroxidase
induction in response to ROS compared to less
aggressive cancer cell lines
 Normal cells are resistant to this effect altogether
due due to their intact glutathione peroxidase
antioxidative defenses.
Wirtitsch M., et al. Oncol Res. 2009
Alschuler 2014
31
SIDE EFFECT
MANAGEMENT: NAUSEA
Ginger
Alschuler 2014
32
Ginger and NV
 Meta-analysis in 2000 of RCTs regarding
efficacy of ginger for N/V collectively
favored ginger over placebo
 Gingerols may increase gastric motility, absorb toxic
compounds, and block nausea feedback
 Galanolactone, a constituent of ginger, is a competitive
antagonist of 5-HT3 receptors.
Ernst, Pittler, Br J Anaesth, 2000
Alschuler 2014
33
Ginger and CINV
 Multisite phase 2/3 randomized multicenter trial.
 The cohort consisted of 644 primarily female patients (90%)
 breast cancer (66%)
 alimentary (6.5%)
 lung (6.1%)
 All of the patients received 5-HT3 receptor antagonist
antiemetics:
 ondansetron (Zofran, GlaxoSmithKline) or granisetron (Kytril, Roche)
— starting on 1st day of chemotherapy of each cycle
 And, began supplementation with either ginger or placebo for 6
days, beginning 3 days before the first day of each
chemotherapy cycle.
 Randomly assigned to ginger: 0.5 g, 1.0 g, or 1.5 g in capsule form,
which was divided into 2 daily doses
Julie Ryan, MD PhD, presented at 2009 Annual Meeting of the American Society of Clinical
Oncologists (ASCO)
Alschuler 2014
34
Ginger CINV: results
 All doses of ginger significantly reduced nausea more than
the placebo on day of chemotherapy (p=0.003)
 The 0.5 g and 1.0 g doses had the greatest effect (p = 0.017
and p=0.036 respectively)
 0.5 g is the equivalent of ¼ teaspoon of ground
ginger and 1.0g is equivalent to ½ teaspoon of
ground ginger.
 The highest dose (1.5g) might not have worked as well as
the lower doses because the patients may have reached the
saturation point with the lower doses.
Alschuler 2014
35
SIDE EFFECT
MANAGEMENT:
MUCOSITIS
L-glutamine, Honey
Alschuler 2014
36
L-Glutamine & mucositis
 Mixed evidence as to effectiveness of oral vs. IV
glutamine for chemotherapy induced mucositis
 One RCT showed 8 g oral glutamine in conjunction
with 5-FU did not effect incidence of severe
mucositis
 One RCT showed 30g oral glutamine in conjunction
with 5-FU decreased the incidence of severe
mucositis
Worthington et al. Cochrane Database Syst Rev. 2011 Apr 13;(4)
Okuno SH, et al. Am J Clin Oncol 1999;22(3):25861.
Choi et al. Clin Nutr. 2007 Feb;26(1):57-62.
Alschuler 2014
37
Honey and chemotherapy-induced
mucositis
• RCT
• N=90 pediatric patients (mean age 6.9 years)
with acute lymphoblastic leukemia and oral
mucositis grades 2 and 3.
• Patients were randomized to: honey, extract
(honey, olive oil, propolis, beeswax = HOPE)
and control groups
• Healing was faster than control for either
honey or HOPE groups (without significant
difference between the two. (p<0.05)
Alschuler 2014
Abdulrhman M et al. Pediatr Hemaotol Oncol. 2012;29(3):285-292
38
PERIPHERAL NEUROPATHY,
HAND FOOT SYNDROME
Glutamine, Vitamin E, Omega-3, vitamin B6
Alschuler 2014
39
Reduction of Paclitaxel-induced
peripheral neuropathy with
Glutamine
 10 grams po TID for 4 days starting 24 h after completion
of first cycle of high dose paclitaxel (825 mg/m(2) given
over 24 h)
 Paired pre- and post-paclitaxel evaluations on 33 patients
who did not receive glutamine and 12 patients who did.
 Statistically significant reduction in severity of peripheral
neuropathy [(P < 0.05)].
 Additional reduction in:



The degree and incidence of motor weakness was
reduced (56% versus 25%; P = 0.04)
deterioration in gait (85% versus 45%; P = 0.016)
interference with activities of daily living (85% versus 27%;
P = 0.001)
Vahdat L, et al. Clin Cancer Res 2001;7(5):1192-7
Alschuler 2014
40
Omega-3: prophylaxis of Paclitaxelinduced neuropathy
• Small study: 57 women undergoing paclitaxel tx
• Randomized to omega-3 fatty acids 640 mg (54% DHA, 10% EPA)
t.i.d. or placebo, for total dose of 1920 mg/day
• Duration: Entire chemo treatment and for one additional month
• Subjective symptoms and electrophysiological measurements
used to calculate “Total Neuropathy Score”
• Incident peripheral neuropathy was sig. lower in σ-3 group:
– 30% (9/30) in omega-3 group vs 59.3% (16/27)
in the placebo group (p = 0.029)
Alschuler 2014
Ghoreishi Z, Esfahani A, Djazayeri A, et al.BMC Cancer. 2012;12(1):355.
41
Vitamin B6 (pyridoxine) and
capecitabine (Xeloda) hand-footsyndrome
• Multicenter, DBRPCT; n = 106 (65% CRC, 35% breast
cancers)
• Palliative single-agent capecitabine (Xeloda) and
pyridoxine 50mg po TID or placebo TID
• Pyridoxine resulted in:
– an increased rate of avoiding capecitabine dose reduction
(37% vs 23% placebo)
– fewer grade ¾ HFS adverse events (9% vs 17% placebo)
• Pyridoxine did not improve or reduce response rate or
progression-free survival
Alschuler 2014
Corrie PG, et al. British J Cancer. 2012;107:585-87.
42
Kaplan-Meier time to 1st dose
modification
Alschuler 2014
43
Pyridoxine dosing
• Of note, a 2010 randomized trial of 56 patients
who received either 200mg vs 400mg of
pyridoxine with capecitabine demonstrated:
– less PPE in both groups, but significantly less in the
400mg group (39% vs. 71%) and no Grade III in the
400mg group vs. 10.7% in the 200mg group.
• However: The 400 mg pyridoxine group had a
worsened tumor response and tended to have
greater tumor treatment failure and shorter time
to treatment failure.
Chalermchai T, et al. Asia Pac J Clin Oncol. 2010 Sep;6(3):155-60
Alschuler 2014
44
Ginseng
(-) acetyl-L-carnitine
FATIGUE
45
Panax ginseng and fatigue
•
The prevalence of fatigue in patients undergoing chemotherapy is reported
to be between 59% - 96% and, in patients receiving radiation therapy,
between 65% - 100%.
– Fatigue can persist 5 to 10 years after diagnosis and treatment
•
Based on encouraging pilot data, the purpose of this trial was to evaluate,
using a double-blind design, the efficacy of 2000 mg/day of American
ginseng (Panax quinquefolius) as therapy for cancer related fatigue and to
evaluate its toxicities.
– 2000mg ginseng or placebo was taken in two doses – am and noon x 8 weeks
• 500mg capsule of pure ground root of Wisconsin ginseng with 3%
gensenosides
– All 341 participants had fatigue
– Participants diagnosed with all cancers except brain or CNS lymphoma within last
2 years; undergoing or completed conventional tx
– Primary endpoint was the Multidimensional Fatigue Symptom Inventory–Short
Form (MFSI-SF)
• Secondary outcomes included the Profile of Mood States (POMS),
specifically the fatigue-inertia and vigor-activity subscales
Alschuler 2014
Barton D, et al. J Natl Cancer Inst, 2013
46
Results
• The primary endpoint of change from baseline in the general
subscale of the MFSI-SF at 4 weeks was 14.4 (standard deviation
[SD] = 27.1) in the ginseng arm (n = 147) and 8.2 (SD = 24.8) in the
placebo arm (n = 153) (P = .07).
• At 8 weeks, there was statistically significant improvement in
fatigue for those on ginseng (n = 138) vs those on placebo (n = 133),
with change scores of 20 (SD = 27) vs 10.3 (SD = 26.1), respectively
(P = .003)
• No significant toxicity
Alschuler 2014
Barton D, et al. J Natl Cancer Inst, 2013
47
Fatigue: Negative study on AcetylL-carnitine
• DBRCT trial of 409 women with stages I-III breast cancer
receiving a taxane-containing regimen were randomized to 3g
acetyl-L-carnitine or placebo.
– There was no improvement in neuropathy. Unexpectedly, ALC
increased CIPN and decreased functional status.
– Thus ALC should not be recommended as a prevention against taxane
caused CIPN
Hershman DL, et al. J Clin Oncol, 2013
48
ADJUNCTIVE CHEMOTHERAPY
PROTOCOLS
49
Doxorubicin: Increase effectiveness
 Fish oil/DHA
 Cancer Lett. 2000 Apr
14;151(2):145-51
 Cancer. 2000 88:1916-28
 Clin Cancer Res. 2001
Jul;7(7):2041-9
 Anticancer Res 2001; 21:2938
 Lipids. 2002 Jun;37(6):549-56
 Br J Cancer. 2009 Dec
15;101(12):1978-85
 Vitamin C
 Cancer Lett 1996;103(2):1839
 Melatonin
 World J Gastroenterol. 2010 Mar
28;16(12):1473-81
 J Pineal Res. 2001 Oct;31(3):206-13.
 Coriolus versicolor (PSP)
 Oncol Rep. 2005 Jul;14(1):145-55
 Sulforaphane
 Mol Cell Biochem. 2009 Oct;330(12):9-22
50
With gratitude to Dr. Daniel Lander, ND, FABNO
Doxorubicin: improve tolerance
CARDIOTOXICITY

CoQ10








Gan To Kagaku Ryoho. 1984 Jul;11(7):1420-7
Drugs Exp Clin Res. 1992;18(10):437-42
Biochem Mol Biol Int. 1995 Aug;36(5):1001-7
J Clin Oncol. 2004 Nov 1;22(21):4418-24
Integr Cancer Ther. 2005 Jun;4(2):110-30
 Grifola frondossa
J Pineal Res. 2001 Nov;31(4):301-7
J Pineal Res. 2001 Aug;31(1):23-30
Histol Histopathol. 2004 Oct;19(4):1101-8
J Cardiovasc Pharmacol. 2005 Aug;46(2):200-10
MUCOSITIS
 Glutamine
Melatonin




MYELOSUPPRESSION
L-Carnitine







Oncology. 1988;45(3):242-6
Drugs Exp Clin Res. 2001;27(1):27-49
Eur J Pharmacol. 2001 Aug 10;425(2):117-20
J Submicrosc Cytol Pathol. 2002 Jul;34(3):315-21
Pharmacol Res. 1999 Apr;39(4):289-95
FASEB J. 1999 Sep;13(12):1501-10.
Drugs Exp Clin Res. 2001;27(1):27-49.

Cell Biol Toxicol. 2008 Jan;24(1):63-73. Epub 2007
May 23
Ashwagandha (Withania somnifera)
 Int Immunopharmacol. 2004
Jan;4(1):91-9
 J Lab Clin Med. 1996
Feb;127(2):223-8
NAUSEA
 Zingiber officinale
 Integr Cancer Ther. 2012
Sep;11(3):204-11
With gratitude to Dr. Daniel Lander, ND, FABNO
51
52
Cytoxan: Improve tolerance
Myelosuppression





Withania somnifera
 Immunopharmacol Immunotoxicol. 1999
Nov;21(4):695-703
 J Ethnopharmacol 1999;67(1):27-35
 J Ethnopharmacol. 1998 Oct;62(3):209-14
 J Ethnopharmacol. 1996 Feb;50(2):69-76
Melatonin
 Neuro Endocrinol Lett. 2009;30(5):582-91
Astragalus membranaceus
 Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002
Jul;22(7):515-7
Coriolus versicolor (PSP)
 Am J Chin Med. 1997;25(1):27-35
 Gen Pharmacol. 1998 Jan;30(1):1-4
Cordyceps sinensis
 Biotherapy. 1990;2(3):199-205
Hemorrhagic cystitis
 Withania somnifera
 Cancer Lett 2000;148(1):9-17
 Melatonin
 J Pineal Res. 2005
May;38(4):272-7
 Cancer Chemother Pharmacol.
2004 Nov;54(5):469-73
Nausea
 Zingiber officinale
 Integr Cancer Ther. 2012
Sep;11(3):204-11
With gratitude to Dr. Daniel Lander, ND, FABNO
53
Cytoxan: Improve Effectiveness
 Coriolus versicolor (PSK)
 Vitamin A
 Chemotherapy. 1987;33(3):2118.
 Fish oil (EPA)
 Aloe vera
 Vopr Onkol. 1986;32(12):38-40.
 Anticancer Res. 1997 JulAug;17(4A):2815-8.
 In Vivo. 2004 SepOct;18(5):543-7
 Folic acid
 Blood. 1998;92(7):2471-6.
With gratitude to Dr. Daniel Lander, ND, FABNO
54
Taxanes: Improve tolerance
Reduce Toxicity

Peripheral neuropathy

Melatonin
 Clin Med Insights Oncol. 2010 Apr 28;4:3541

L-Glutamine
 Clin Oncol (R Coll Radiol). 2005
Jun;17(4):271-6
 Clin Cancer Res 2001;7(5):1192-7

Vitamin E
 J Pain Symptom Manage. 2006
Sep;32(3):237-44

Acetyl-L-Carnitine
 J Clin Oncol. 2013 Jun 3

Mucositis

L-Glutamine
 Ann Pharmacother. 2000 Mar;34(3):300-3

Nausea/vomiting

Zingiber officinale
 Integr Cancer Ther. 2012 Sep;11(3):204-11
Increase Effectiveness
 Curcumin
 Cancer Biol Ther. 2010 Jan;9(1):8-14
 J biol Chem. 2005 Feb 25;280(8):63018
 Coriolus versicolor
 Int J Oncol. 2012 Apr;40(4):905-13
 Fish oil
 Prostate. 2008 Nov 1;68(15):1635-46
 Eur J Cancer Prev. 2005 Jun;14(3):26370
 J Am Coll Nutr. 2011 Aug;30(4):265-73
 Gamma-linolenic acid
 Eur J Cancer. 2001 Feb;37(3):402-13
 Vitamin C
 Cancer Lett 1996;103(2):183-9
With gratitude to Dr. Daniel Lander, ND, FABNO
-Platinum
(Oxaliplatin, Carboplatin, Cisplatin)




Vitamin E [reduce CIPN]

J Clin Oncol. 2003 Mar 1;21(5):927-31

Argyriou et al., Neurology, 2005
Ginkgo biloba (> 48 hr away from chemo.) [reduce CIPN]

Nippon Jibiinkoka Gakkai Kaiho. 1999 Jul;102(7):907-17. [in vitro]

Toxicol Appl Pharmacol. 2004 Apr 1;196(1):169-75. [mouse study]
L-carnitine [reduce fatigue, protect kidneys]

Arch Biochem Biophys. 2002 Sep 1;405(1):55-64. [animal study]

Arch Toxicol. 2005 Jul;79(7):406-13. [in vitro]
Milk thistle [synergistic]

Int J Cancer. 2003 Sep 20;106(5):699-705
55
Fluorouracils (5-FU, FUDR) or pro-drug Xeloda

Fish oil [synergistic & reduced intestinal toxicity]



Curcuma longa (curcumin) [synergistic]


Invest New Drugs. 1990 Feb;8(1):57-63
Green tea [synergistic, reduced hepatotoxicity]




Support Care Cancer. 1997 Mar;5(2):126-9
Pyridoxine (vitamin B6) [reduced PPE]


Chemotherapy. 2006;52(1):23-8. [In Vitro] J Med Food. 2004
Summer;7(2):117-21. [In Vitro]
Melatonin [synergistic; increased overall tolerance]


Cancer Chemother Pharmacol. 2005 Jan;55(1):12-20. [in vitro]
Eur J Gastroenterol Hepatol. 2004 May;16(5):479 85 [rodent study]
Clin Cancer Res. 2001 Dec;7(12):4220-9. [In Vitro]
Nippon Geka Gakkai Zasshi. 1998 Jun;99(6):391-5. [Human Study]
Nippon Geka Gakkai Zasshi. 1998 Jun;99(6):391-5 [In vivo]
Ascorbic acid [increased overall tolerance]

In Vivo. 2003 May-Jun;17(3):289-92
56
Dermatitis, Fatigue, Lymphedema
RADIATION
57
58
Radiation-induced dermatitis
 Prevention
 Topical
 Calendula officinalis
 J Clin Oncol. 2004 Apr 15;22(8):1447-53
 Cochrane Database Syst Rev. 2009 Apr 15;(2):CD004845
 Semin Oncol Nurs. 2011 May;27(2):e1-17
 Silymarin
 Strahlenther Onkol. 2011 Aug;187(8):485-91
 Avoid Aloe vera as it is not effective
 Oncol Nurs Forum. 2001 Apr;28(3):543-7
 Int J Radiat Oncol Biol Phys. 1996 Sep 1;36(2):345-9
 Cancer Nurs. 2002 Dec;25(6):442-51.
 Oral Curcumin
 Radiat Res. 2013 Jun 7
 Oral vitamin E 400iu daily x 6 mo after radiation
 Int J Radiat Oncol Biol Phys. 2013;85(3):604-8
 Treatment
 Manuka honey dressings
 Acta Oncol. 2006;45(5):623-4
With gratitude to Dr. Daniel Lander, ND, FABNO
59
Radiation-induced fatigue
 Exercise - mixed results
 Improvement in fatigue






J Support Oncol. 2009 Sep-Oct;7(5):158-67
J Clin Oncol. 2009 Jan 20;27(3):344-51
Oncol Nurs Forum. 2008 Nov;35(6):909-15
Oncol Nurs Forum. 1997 Jul;24(6):991-1000
Cancer Pract. 2001 May-Jun;9(3):119-27
Psychooncology. 2005 Jun;14(6):464-77
 No change in fatigue
 Cancer Nurs. 2010 Jul-Aug;33(4):245-57
 Am J Phys Med Rehabil. 2010 Aug;89(8):611-9
 L-carnitine: improvement
 Ann N Y Acad Sci. 2004;1033:168-76
With gratitude to Dr. Daniel Lander, ND, FABNO
60
Radiation-induced lymphedema
 10/12 patients with arm edema showed a
circumference reduction of the edematous limb and
improvement in the Skin-Fold Index by 23.3 points
 Selenium has a positive effect on secondarydeveloping lymphedema caused by radiation therapy
alone or by irradiation after surgery
Micke O. et al. Int J Radiat Oncol Biol Phys. 2003 May 1;56(1):40-9
With gratitude to Dr. Daniel Lander, ND, FABNO
61
Radiation-induced immune suppression
 Astragalus [also reduced fatigue]
 Clin Invest Med. 2012;35(1):E1-11 {human}
 Fitoterapia. 2011;82(3):383-92 {animal}
 Phytother Res. 2011;25(5):644-53 {animal}
 Withania somnifera (ashwaghanda) [also radiosensitizer]
 Toxicol In Vitro. 2011;25(8):1803-10 {in vitro}
 J Altern Complement Med. 2009; 15(4):423-30 {in vivo}
 Eur J Cancer. 2009;45(8):1494-509 {animal}
 Melatonin
 (refer to previous references)
 Medicinal mushrooms
 (refer to previous references)
ENDOCRINE THERAPIES
62
Endocrine Therapies
Universal Side Effects
Tamoxifen vs. Arimidex
Hot Flashes
Arthralgia
Sexual Dysfunction
Cognitive changes, but…*
 Thromboembolism
(Tam>Arim)
 Bone Loss (Arim > Tam)




 Older pts. with BrCA receiving
TMX post chemotx have better
verbal ability and processing
speed.
 TMX has been shown to slow
cognitive decline in postmenop.
women with Alzheimer’s disease
 Anxiety/Depression
 TAM associated with loss
in premenopausal women
only
 Vaginal Bleeding (Tam>
Arim)
GOAL: Lessen Side Effects without interfering with
treatment efficacy.
*Newhouse P. et al. Neuropsychopharmacology. 2013;38(13):2632-43
63
64
Bone health
 Calcium-Age specific, but generally about 1500mg
total from diet and supplements
 Magnesium- At least half the dose of the calcium,
perhaps more if no loose stool
 Vitamin D- ideal serum level debatable, my bias: mid to high range
(45-65 ng/dL)
 Vitamin K2 (MK-4) at high doses, esp. for the young or those with
osteopenia



Minimum, 15 mg/day. Therapeutic dose: 15mg tid
Contraindication: Use of Coumadin/Warfarin
See summary paper on use: Sept 2009 issue of Natural Medicine Journal
(www.naturalmedicinejournal.com)
 Other bone minerals/trace minerals- silica, manganese, boron,etc.
(okay in dietary amounts)
 Collagen support- adequate protein intake, adequate bioflavonoids
 Consider home-made soup stocks using grass finished beef, wild
game, etc
With gratitude to Dr. Tina Kaczor, ND, FABNO
Arthralgias from TMX or AIs
65
 Can switch drugs until one is found that is tolerable. Each AI
has a different reactions/side effects in patients
 Carpal tunnel syndrome with AI’s can preclude their use
 Vitamin D: >66 ng/dL found to reduce arthralgias from
letrozole. (Citation below)
 This serum level was achieved using 50,000iu vitamin D3 weekly
 Acupuncture
 Treat much like osteoarthritis




Remove inflammatory foods
Fish oil
Glucosamine sulfate
Curcumin, Boswellia, Enzymes
Khan QJ et al. J Breast Cancer Res Treat. 2010 Jan;119(1):111-8.
With gratitude to Dr. Tina Kaczor, ND, FABNO
66
Sexual
dysfunction
 Desire
 Self Image/ Confidence
 Counseling – refer patient
 Vulvar-vaginal atrophy
 Lubricants: Correct osmolality
Dew J, Wren B, Eden J. Climacteric. 2003;6(1):45-52.
 Vitamin E
With gratitude to Dr. Tina Kaczor, ND, FABNO
The Future? Integrative Oncology
 Clinically validated natural therapies combined with
active conventional treatment is a rational and effective
treatment strategy.
 The future of oncology is increasingly reliant upon
targeted therapies
 drugs that interfere with molecules necessary for cellular
survival and proliferation
– Integrative co-management of monoclonal antibodies and small molecules
mostly empiric
– It is critical to understand the mechanism of action of each drug as well as
common and serious toxicities
• An integrative approach to cancer treatment can
positively transform cancer care and reduce the suffering
caused by this illness.
Alschuler 2014
67
Resources
Alschuler 2014
68
Books and Radio
Definitive Guide to Cancer: An Integrative Approach to
Prevention, Treatment and Healing (3rd ed.)
Definitive Guide to Thriving After Cancer
By Lise Alschuler, ND, and Karolyn A. Gazella
Five To Thrive Live!
Talk radio
Podcasts on
iHeart.com (search:
Five To Thrive Live)
www.FiveToThrivePl
an.com
www.DrLise.net
www.ListenAndCare.
com
Alschuler 2014
69
Q & A Session
© Genova Diagnostics
Tests referenced in Parts I and II
•
•
•
•
•
•
•
CV Health/ Cardiovascular Health Profile
MetSyn Guide
Adrenocortex Stress Profile
EstroGenomic Profile
Vitamin D Assay
Comprehensive Thyroid Assessment
Toxic Effects CORE
71
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