Ovarian cancer integrative oncology: Principles, Practice and …/media/Images/Swedish/CME1/... ·...

Innovations in Gynecologic Cancer Care 5/12/2017

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Ovarian cancer integrative oncology: Principles, Practice and Outcomes

Leanna J. Standish ND, PhD, MSAOM, FABNOBastyr University Research InstituteUW School of Medicine, Radiology

May 12, 2017Swedish Hospital lecture


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• Textbooks

• Journals

• International society

• Board certification

• Federal funding• NCI• NCCAM NCCIH

Integrative oncology is a new emerging medical discipline with:

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Professional societies and board certification

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Board Certification in naturopathic oncology 2004 FABNO


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Basic philosophy of integrative oncology is that modalities such as acupuncture, nutrition, psychological counseling, some specific botanical and fungal ‘supplements’ can improve QOL.

Basic philosophy of naturopathic oncology is that 1) the natural world and its medicine, both known and unknown, is able to provide

safe and effective treatments for cancer patients to improve high quality survival; 2) cancer is also a mind‐body problem and requires psychological interventions.

Goals of advanced IO in ovarian cancer includes improve chemo sensitivity, decrease dose‐limiting toxicities of chemotherapy, reduce risk of recurrence after primary cancer treatment, palliation of symptoms and improving quality of death & dying.


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Plant Chemotherapy derivative

Pacific Yew (Taxus brevifolia) paclitaxel, docetaxel, albumin‐bound paclitaxel

Pink & Red Periwinkle (Catharanthusroseus)

vincristine and vinblastine, vinorelbine

Chinese “Happy Tree” (Camptothecaacuminata)

camptothecin

Mayapple (Podophyllum peltatum) teniposide and etoposide

Most of our best chemotherapy drugs originated from plants

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Curcumin

Green tea

Bromelain

Quercetin

Artemisinin

Ascorbate

Melatonin

Trametes versicolor(Lu and Disis UW TVG 2011-2012)

NFKappaB inhibitor Increase P53 expression

MTOR (serine/threonine kinase) inhibitor; P21 upregApoptosis by free radical MOA

cysteine proteinases with antimetastatic, antithrombotic antiedematous, fibrolytic,

histone deacetylase inhibitor Tyrosine kinase inhibitor

Iron oxidative stress

Oxidative burst in malignant cells

Proteosome inhibitorAnti-estrogen

Immune modulator viaToll-like 2 receptor agonistDectin-1 agonistInflammasome agonist

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Molecular targets in ovarian cancer

• EGFR• VEGF• PD‐L1• MTOR

• STAT‐3• AMPK

• Glucose metabolism

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Evidence to support core therapies in ovarian cancer

• Pro‐oxidant cytotoxic single agent therapies• Botanical• Fungal• Hormones• Antioxidants• FDA approved drugs off label• Psychoneuroimmunologic

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Pro‐oxidant therapies single molecule therapies

High dose parenteral ascorbate 25 – 100 grams/infusion

Ma, Y., J. Chapman, et al. (2014). "High‐dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy." Sci Transl Med 6(222): 222ra218.

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In vitro Depleted (ATM)/adenosine monophosphate–activated protein kinase (AMPK) pathwaymTOR) inhibition and cytotoxic death in ovarian cancer cells.

Animal modelsParenteral ascorbate + Taxol/Carboplatin synergistically inhibited ovarian cancer in mouse models

IV Vitamin C therapy in ovarian cancer?Ma et al 2014

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Reduced chemotherapy-associated toxicity in patients with ovarian cancer

Improved PFS? Improved OS?

IV vitamin C RCT in women with ovarian cancer

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Fig. 4. Reduction of toxicity and better PFS and OS in ovarian cancer patients after adding ascorbate to chemotherapy.

Yan Ma et al., Sci Transl Med 2014;6:222ra18

Published by AAAS12


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Botanical therapies used in the treatment of ovarian cancer

• Epicatechins from green tea• Curcumin• Mistletoe• Indole‐3‐carbinol from broccoli• Quercetin• Bromelain• Artemisinin

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Green tea epicatechin


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15From Lise Alschuler ND, FABNO


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Green teaepicatechinactive in ovarian, breast and colon cancer.

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Trudel, D., D. P. Labbe, et al. (2013). "A two‐stage, single‐arm, phase II study of EGCG‐enriched green tea drink as a maintenance therapy in women with advanced stage ovarian cancer." Gynecol Oncol 131(2): 357‐361.

Trudel, D., D. P. Labbe, et al. (2012). "Green tea for ovarian cancer prevention and treatment: a systematic review of the in vitro, in vivo and epidemiological studies." Gynecol Oncol 126(3): 491‐498.


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(no copyright)

Curcumin

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Turmeric, Curcumin

Oral bioavailability of curcuminoids is low.IV curcumin is likely necessary for full anti‐cancer effect.Active across many solid tumor types.

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nuclear factor erythroid 2–related factor 2 (Nrf2) controls anti‐oxidant response to ROS.

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Curcumin in vitro dataIncreases chemo and radiosensitivity (Saydmohammed, Joseph et al. 2010; Yallapu, Maher et al. 2010),

STAT‐3 (Pan, Yang et al. 2008)

AMPK (He, Wang et al. 2016) (Bondi, Emma et al. 2017)

Induces apoptosis (Seo, Kim et al. 2016)

Lowers drug resistance (Li, Zhou et al. 2016; Zhang, Liu et al. 2017)

Lowers platinum resistance (Terlikowska, Witkowska et al. 2014)20


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The adverse side effects of cancer treatment can often be attenuated with oral curcumin.

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Mistletoe lectins

Mistletoe in vitro and animal data and clinical data (Schumacher, Feldhaus et al. 2000; Piao, Wang et al. 2004)

Widely used in Europe – SQ and IVimproves QOL in ovarian cancer patients

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Indole‐3‐carbinol Indole‐3‐carbinol In vitro data showing ovarian cancer sensitizationto chemotherapy (Taylor‐Harding, Agadjanian et al. 2012).

Vulvar cancer 200 mg bid po clinical trial (Naik et al2006)

Naik, R., S. Nixon, et al. (2006). "A randomized phase II trial of indole‐3‐carbinol in the treatment of vulvar intraepithelial neoplasia." Int J Gynecol Cancer 16(2): 786‐790.

Taylor‐Harding, B., H. Agadjanian, et al. (2012). "Indole‐3‐carbinol synergistically sensitizes ovarian cancer cells bortezomib treatment." Br J Cancer 106(2): 333‐343. 23


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Antioxidants

SeleniumSelenium supplementation reduces risk of ovarian cancer in African American women (Terry, Qin et al. 2017). We use it in BRCA positive patients

Terry, P. D., B. Qin, et al. (2017). "Supplemental Selenium May Decrease Ovarian Cancer Risk in African‐American Women." J Nutr 147(4): 621‐627.

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Higher fungiTrametes versicolor

Trametes versicolor: Over 50 trials in colorectal, a few on breast and lung cancer

No clinical trials in ovarian cancer.

NKCA predicts PFS in ovarian cancer patients (Garzetti, Cignitti et al. 1993)

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Turkey Tail: Trametes (Coriolus) versicolor, commonly called Turkey Tail is a small flexible polypore fungus that is an important part of the forest ecology as a recycler of dead and dying trees in forests throughout the world. In Japan, T. versicolor is know as kawaratake and in China, the fungus is called Yun Zhi or “cloud-like fungus”

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Hailing Lu, MD, PHD

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Strong PSK pre-clinical and clinical data Complex mechanism of action – activates

innate immune system via multiple pathways Phase I trial of PSK or placebo + her2neu

peptide vaccine + trastuzumab N=30UW/Bastyr/NCCAM partnership

(Disis/Salazar/Standish)NCT01922921

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Ferry DR et alPhase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. ClinCancer Res. 1996 Apr;2(4):659-68.

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Quercetin (3,3',4',5,7‐pentahydroxyflavone)

1.Inhibits the growth of tumor cells2.Prevents cancer metastasis and suppress cancer cell proliferation in animal models.3.Inhibits signal transduction targets including tyrosine kinases, protein kinase C,

and phosphatidyl inositol‐3 kinase4.In one patient with ovarian cancer refractory to cisplatin, following two courses of

quercetin (IV 420 mg/m2), the CA 125 had fallen from 295 to 55.

5. Can be safely administered by i.v. bolus at a dose injection (Ferry et al. 1996)

BUT contraindicated with chemotherapy

Li, N., C. Sun, et al. (2014). "Low concentration of quercetin antagonizes the cytotoxic effects of anti‐neoplastic drugsin ovarian cancer." PLoS One 9(7): e100314.

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Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction?Integr Cancer Ther. 2008 Dec;7(4):311-6. Beuth J.

• Anti-metastatic• Prevents and treats post-surgical fibrosis, • axillary webbing following breast cancer surgery • lymphedema

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Bromelain for lymphedema?

Ho, D., J. Jagdeo, et al. (2016). "Is There a Role for Arnica and Bromelain in Prevention of Post‐Procedure Ecchymosis or Edema? A Systematic Review of the Literature." Dermatol Surg 42(4): 445‐463.

For 6 weeks after surgery bromelain 750mg bid ac to prevent post‐surgical fibrosis, bowel obstruction and lymphedema

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Crespo-Ortiz MP, Wei MQ.Antitumor activity of artemisinin and its derivatives: from a well-known antimalarial agent to a potential anticancer drug. J Biomed Biotechnol. Epub 2011 Nov 22.

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Hormones and peptides

Melatonin 10‐40 mg h.s.

Ov ca pts have lower serum melatonin levels (Zhao, Wan et al. 2016)

IL2+ MLT in salvage ovarian cancer pts stabilized disease in 50% of pts (Lissoni, Ardizzoia et al. 1996)

in vitro decrease in E‐caderin, decrease VEGF expression, decrease stemness (Akbarzadeh, Rahbarghaziet al. 2017)

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Vitamin D 5000 iu/day 45‐70 mg/dlVit D3 inhibits migration and growth of ov ca cells (Abdelbaset‐Ismail, Pedziwiatr et al. 2016)

Vit D decreases progression in animal models (Liu, Hu et al. 2016)

Low 25‐OH‐vitamin D levels predict recurrence (Granato, Manganaro et al. 2016)

Abdelbaset‐Ismail, A., D. Pedziwiatr, et al. (2016). "Vitamin D3 stimulates embryonic stem cells but inhibits migration and growth of ovarian cancer and teratocarcinoma cell lines." J Ovarian Res 9: 26.

Liu, L., Z. Hu, et al. (2016). "Vitamin D postpones the progression of epithelial ovarian cancer induced by 7, 12‐dimethylbenz [a] anthracene both in vitro and in vivo." Onco Targets Ther 9: 2365‐2375.

Granato, T., L. Manganaro, et al. (2016). "Low 25‐OH vitamin D levels at time of diagnosis and recurrence of ovarian cancer.“Tumour Biol 37(2): 2177‐2181.

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Drugs off label

• Metformin• Inhibits metastasis of ovarian cancer by inhibiting ECM interactions, neovascularization (Wu, Li et al 2012)

• Prevents ovarian cancer growth in conjunction with calorie restriction (Al‐Wahab 2015)

• Low dose naltrexone• Synergizes effects of cisplatin (Donahue et al 2011)

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Metabolic support for chemotherapy?

Long‐Term Outcomes of the Treatment of Unresectable (Stage III‐ IV)Ductal Pancreatic Adenocarcinoma Using Metabolically SupportedChemotherapy (MSCT): A Retrospective Study. JOP. J Pancreas 2016 Jan 08; 17(1):36‐41.Iyikesici et al (2016)

14 hr pre‐chemotherapy water fastHumulin 5 units 20 min before start of chemotherapy infusionKetogenic diet before and after

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FundingBudge Brown, Lorraine Masterson, NCCAM, the Hecht Foundation and Bastyr University.

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Whole-person, full scope of practice, health services oriented prospective studies of IO survival outcomes compared to …..

Tumor registries1. National (e.g. SEER)2. regional tumor (e.g. WA State Cancer Surveillance System) registries

Published phase III pharmaceutical trials with PFS and survival outcomes.

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Bastyr Cancer Outcomes Study 2009‐2016 N = 694


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BIORC adverse events Adverse Event (AE)

Serious Non‐Serious

Chills (2) x

PsychiatricDisorder Other

x

Bruising x

Respiratory Otherx

Anemia x

Hypoglycemia x

Pain x

Vomiting (4) x

Dizziness x

Tracheal obstruction x

Hot flashes (2) x

Nausea (3) x

Allergic reaction x

Headache x

Diarrhea x

Dyspnea x

Cough x

Adverse event (AE) data is collected from staff reports. AE’s are categorized and reported using the NCI‐CTAE system.

A serious adverse event is an event that results in any of the following outcomes: death, life threatening event, inpatient hospitalization, persistent or significant disability or incapacity.

Data collected since 1/2012 to 10/1/2013. 24 AE’s reported on 13 patients

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AbraxaneIniparib +carboplatin + gemcitabine

eribulin

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Treatment dosage Frequency Duration

Cost for course of treatment

($)

Bromelain 1500 mg daily 365 days 627.80Curcumin 3000 mg daily 365 days 450.17Green tea 2000 mg daily 365 days 87.38IV Artenusate 120 g weekly 12 months 12,064.00IV ascorbic acid 100 g weekly 12 months 12,064.00Melatonin 20 mg daily 365 days 24.30Mistletoe injections 1 injection weekly 12 months 236.85

T. versicolor mushroom 3000 mg daily

365 days608.33

Vitamin D3 5000 iu daily 365 days 14.45

Wobenzyme 3 tablets daily 365 days 178.98

Total Cost 26,356.26

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Ovarian cancer (Stage IV at FOC)

1 year 2 years 3 years

Survival Rate 75% 42.9% 32.1%

Stage IV ovarian cancerN =12

BIORC median survival 2 yearsSEER median survival 2 years

SEER data


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At 3 years 83% of stage III ovarian cancer patients are alive.

SEER national data At 3 years 49% are still alive

IO may prevent (or delay) recurrence.

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OS = 4.5 years in stage 1-3

OS = 2.0 yr

Work completed by Sherry Su, ND 2016

Rose 2016OS = 3.6 yr

OS from Bastyr intake

Rose, P. G., J. J. Java, et al. (2016). "Disease extent at secondary cytoreductivesurgery is predictive of progression-free and overall survival in advanced stage ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study." Gynecol Oncol 143(3): 511-515.


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Bastyr ovarian cancer outcomes (2009‐2016) N =42 consecutively enrolled women with ovarian cancer.

Stage at dx Total

1‐3 33

4 6

Unknown 3

Total 42

Stageat FOC Total

1‐3 27

4 15

Total 42

Main outcomes = median PFS and median OS

48Work completed by Jinda Chaijinda, ND candidate 2017.


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PFS in stage 1‐3 ovarian cancer patients AFTER DX treated at Bastyr University (N = 27)

PFS = 24 mo.

How does this compare to published chemotherapy trials? Median PFS ranges from 9 mo(Mouratidou 2007) to 29.7 mo (Dittrich 2003) . Rose (2016 median PFS = 13.8 mo)

Rose et al 2016N = 555 PFS = 13.8 mo

Dittrich 2003PFS = 29.7 mo

Bastyr median PFS = 24 mo.

Dittrich, C., P. Sevelda, et al. (2003). "Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients. 10‐year results of a prospective randomised phase III study comparing carboplatin‐cisplatin with cyclophosphamide‐cisplatin." Eur J Cancer 39(8): 1129‐1140.


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PFS from Bastyr intake (N = 33) = 22 months

PFS = 15.7 mo (Sundar et al 2012)

50Thanks to Fred Dowd for all KM curves.


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Median OS in stage 1‐3 from DX = 46 months

Rose 2016Median OS = 43 mo

Sundar 2012Median OS = 30.6 mo

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Median OS in stage 1‐3 from diagnosis with IV therapy (N = 29) and without (N = 13) 47 months in both groups

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Median OS in stage 4 ovarian cancer patients (N = 6) from Bastyr intake in IV (N = 15) vs non‐IV (N = 13) treated women

Median OS = 22 mowithout IV

Median OS with IV therapy = 26 mo

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Bastyr PFS and OS results?

Not great but better than concurrent published trials in ECOG 0‐1 women with ovarian cancer.

Maybe IV high dose ascorbate helps improve PFS and OS in stage 4 ovarian cancer patients.

How can we improve? What results are other IO clinics getting in ovarian cancer?

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CUSIOSThe Canadian/US Integrative Oncology Study

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Advanced Integrative Oncology treatment for patients with advanced stage cancer: A prospective outcomes study

Canadian PI: Dugald Seely, ND, MSc, FABNOUS PI: Leanna Standish, PhD, ND, FABNO

Research Team: Julie Ennis, Ellen McDonell – OICC/CCNMLinda Dale, Peich Cheng, Fred Dowd - Bastyr


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CUSIOS

(1) Measure survival of late stage breast, colorectal,ovarian and pancreatic cancer patients whoreceive AIO treatments

(2) Describe AIO treatments recommended bynaturopathic oncologists for late stage cancer

(3) Pilot the collection of health‐related quality of life(HR‐QOL) data on a subset of Canadian AIOtreated patients.

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Advanced integrative oncology therapies

• Mistletoe therapy SQ and IV• IV ascorbate + Artenusate• Locoregional hyperthermia • Whole body hyperthermia• Metabolic support for chemotherapy (fasting and insulin potentiation)

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Advanced integrative therapies used by CUSIOS clinical sites for stage 3‐4 ovarian cancer

Type of treatment AIO Canadian clinic A (IOCC) AIO U.S. Clinic 5 (Bastyr)

ORAL

Coriolus Versicolor – 3gm qdTheracurmin 120mg bidQuercetin – 500mg bidLDN – 3‐4.5 mg qdMetforminMagnesium 450mg qdVit D – 1‐1000iu/day or more dependent on serum vit DFish oil – combined 2000mg of EPA/DHA

Curcumin 4000 mg/dayTrametes versicolor 1500 mg bidBromelain 1500 mg bidProbioticsQuercetin 750 mg bidWobenzyme 3 tables QIDModified citrus pectin 6 grams bidLow dose naltrexone 4.5 mg h.s.Vitamin D3 5000 iu/day

INJECTABLES

IV CIV mistletoe or subQ

IV ascorbate (first line)IV ArtenusateIV nutritionIV hydrationVitamin B complex i.m.Mistletoe SQ

TOPICAL Castor oil if tendency to bowel obstruction or constipation Castor oil pack

PHYSICAL MEDICINE AcupunctureHyperthermiaHyperbaric oxygenSauna/sweat

EXERCISEDependent on capacity 20‐40 mins moderate to vigorous activity daily

ECOG 0 ‐ 20 min aerobic dailyECOG 1‐2 ‐ 20 min walking daily

MIND‐BODY

YogaMeditationNature walks

Qi gong classYoga classMBMSRHeartMath biofeedbackretreats 58


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CUSIOS Clinical Sites

Canadian SitesC1 Ottowa Integrative Cancer Center (OICC) Dr. Seely Ottawa, ONC2 Vital Victoria Naturopathic Clinic Ltd (VVNC) Dr. McKinney Victoria, BCC3 Integrated Health Clinic Cancer Care Centre

(IHCCC) Dr. Parmar Fort Langley, BC

C4 Marsden Centre for Excellence in Integrative Medicine (MCEIM) Dr. Marsden Vaughan, ON

C5 HealthSource Integrative Medical Centre (HSIMC) Dr. Reid Kitchener, ON

American SitesU1 Shelby Naturopathy, PLLC (SNP) Dr. Standish Seattle, WAU2 Naturopathic Specialists, LLC (NSL) Dr. Rubin Scotsdale, AZU3 Salish Cancer Center (SCC) Dr. Reilly Fife, WAU4 Lokahi Health Center (LHC) Dr. Traub Kailua Kona, HIU5 Tree of Health Integrative Medicine (THIM) Dr. Naydis Woodinville,

WAU6 Red Cedar Wellness Center (RCWC) Dr. Sweet Bellevue, WA


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CUSIOS Protocol overview

N = 400• Study objectives:

• Aim 1: Measure survival of advanced stage breast, colorectal, ovarian and pancreatic cancer patients who receive AIO treatments

• Aim 2: Describe AIO treatments recommended by naturopathic oncologists for advanced stage breast, colorectal, ovarian and pancreatic cancer patients across the treatment cohort.

• Aim 3: Pilot the collection of health-related quality of life (HRQOL) data on a subset of Canadian AIO-treated patients.

• Participants: The study sample size is 400 advanced stage cancer patients: 150 with stage 4 breast cancer, 150 with stage 4 colorectal cancer, 50 with stage 3 or 4 ovarian, and 50 with stage 3 or 4 pancreatic cancer.

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CUSIOS Participants

Participants: The study sample size is 400 advanced stage cancer patients: • 150 with stage 4 breast• 150 with stage 4 colorectal• 50 with stage 3 or 4 ovarian• 50 with stage 3 or 4 pancreatic

65, 40%

46, 28%

30, 19%

21, 13%

Cancer Type Distribution

BreastColorectalPancreaticOvarian

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N = 40050 with stage 3 or 4 ovarian cancer

-1000

100200300400500

Jul

Aug

Sep Oct

Nov

Dec Jan

Feb

Mar

Apr

May Jun

Jul

Aug

Sep Oct

Nov

Dec Jan

Feb

Mar

Apr

May Jun

Jul

Aug

Sep Oct

Nov

Dec Jan

Feb

Mar

Apr

May Jun

2015 2016 2017 2018

Part

icip

ants

Months

CUSIOS Recruitment

Goal

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RESTART: Learning to Reduce Stress and Anxiety after Cancer Treatment

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RESTART Funding Sources

FHCRC (RESTART 5 Subject Feasibility Study)Rivkin Foundation (RESTART 20 Subject Pilot Study)

Total N = 25

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Fred Hutchinson Cancer Research CenterSeattle, WA

RESTART PRINCIPAL INVESTIGATORM. Robyn Andersen, PhD


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Targeted natural medicine cancer treatment pathwaysAdapted from Lutendorf 2011 and modified by Peih Chiang, ND.

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Can shift to heart rate coherence affect thetumor bed?HEARTMATH is well established method to teach patients to induce a cardiac coherence with 0.1 Hz.

CARDIAC COHERENCE is defined as sinusoidal change in HR over time = high amplitude power at 0.1 Hz.

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RESTART Study TeamPRINCIPAL INVESTIGATOR

M. Robyn Andersen, PhD,

FHCRC Member , Translational Research Program at FHCRC

University of Washington (UW), Clinical Associate Professor in the School of Public Health and Community Medicine

PROJECT MANAGER :

Marcia Gaul

FHCRC Project Manager

DATABASE (DB) MANAGER/PROGRAMMER

Shelly Hager

FHCRC Systrm sAnalyst/Programmer

HEARTMATH CONSULTANT

Peih Chiang, ND

HeartMath Consultant for RESTART

Bastyr University Research Investigator

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RESTART Study Aims (N =30)1. To tailor the Heart Math general intervention to best meet the needs of an OC survivor population. 2. To pilot data collection instruments that will be used in a larger trial of the intervention that would include measurement of HRQOL, distress, changes in HRV associated with the intervention, and biomarkers of stress and inflammation.

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[email protected]

425‐602‐3166

See appendix for CAM symptom management therapies.

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Thank you.

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Integrative oncologysymptom management in ovarian cancer

Table XX. Advanced integrative oncology treatment for symptom management

Symptom or side effects

CCNM Bastyr

Anorexia Whey protein, melatonin, fish oil

IV nutrition

Abdominal pain Acupuncture Castor oil pack Massage

Castor oil packacupuncture

anemia B complex – oral

Vitamin B complex im weeklyMarrow Plus TCM formula

leukopenia AstragalusMistletoe subQ Coriolus

Acupuncture Trametes versicolor Withania

Bone pain AcupunctureBenadryl Curcumin

Claritin Ibuprofen Symphytum homeopathic Eupatorium homeopathic

dyspnea AcupunctureYoga Breath work hypnotherapy

Nebulized GSH +NACBromelain quercetin

diarrhea Acupuncture Tincture of opium

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Depression Fish oil – high EPA/DHA (3:1) 2000mgPascoeflair qdCounselingYogaExercise

CitalopramSt John wortB complexpsychotherapy

Anxiety Neurapas qdGABAHypnotherapyCounselingMassageNature walksExercise

CitalopramMeditation trainingRescue Remedy

Dyspareunia ReplensEstrogen cream suppository

1 mg estriol vag suppository

Apthous ulcers (stomatitis) L‐glutamineCoconut oil

l‐glutaminevit E topicallyViscous lidocaine

GERD DGLMelatoninFood hygiene (chewing, mixing foods)Reduce anxiety

DGL chewables

gastritis DGL Digestive enzymes

DGL chewablesMediclear

hypoalbuminemia Whey protein IV aminosyn

ascites Acupuncture BromelainWobenzyme

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Pleural effusion BromelainWobenzyme

osteoporosis ProBones (mix of minerals)Cal/Mag Vit D

Osteoprime formula

insomnia MelatoninL‐theanine5‐HTPPassionflowerneurapasSleep hygiene – reading, no phone or tv

Melatonin

Ileus ER acupunctureNausea and vomiting Ginger tea or tabs Ginger tea

Nux vomica homeopathic

Cerebral edema Boswellia – 1500mg qd Boswellia 3000 mg/day

Ankle edema AcupunctureWhey proteinVit C + bioflavanoids

Wobenzyme

Peripheral neuropathy AcupunctureALABenfotiamineLiposomal GSH

l‐glutamineIV GSH

Elevated blood sugar BerberineALAMetformin

MetforminDiabetone

Nerve pain AcupunctureEpsom salt baths

Hypericum homeopathic

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‘chemo brain’ Gingko BilobaMelatoninAcetyl L‐carnitine

Acetyl‐carnitine (Memoractive)

lymphedema AcupunctureProteolytic enzymesLymphatic drainage

WobenzymePhysical therapy by lymphaticExpertApis homeopathic

Hot flashes Estrovera (Siberian rhubarb)RemifeminSoySageAcupuncture

SJW + remifemin (black cohosh)citalopram

Constipation Magnesisum glycinate Triple magnesium

Hand and foot erythema Hand to Heal creamB‐complex

Vitamin B6 50‐150 mg/day in am with food

Nose bleeds Remove/reduce curcuminVit C + bioflavanoids

Hawthorne berry extract ½ tsp bid

Cardiotoxicity and poor ejection fraction CoQ10L‐carnitine

coQ10 100 mg/dayHawthorne Berry ½ tsp bid

Generalized pruritus Oatmeal filtered baths quercetin

Arthralgia & myalgia AcupunctureCurcuminFish oilCoQ10

CurcuminMagnesiumEpson salts bathAcupuncture

Thrombocytopenia Sesame oil – 2 Tbsp oral or topical Sesame oil 2 tablespoon oral or topical

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