Innovations in Gynecologic Cancer Care 5/12/2017
Ovarian cancer integrative oncology: Principles, Practice and Outcomes Leanna J. Standish ND, PhD, MSAOM, FABNO Bastyr University Research Institute UW School of Medicine, Radiology May 12, 2017 Swedish Hospital lecture
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Integrative oncology is a new emerging medical discipline with:
• Textbooks • Journals • International society • Board certification • Federal funding • NCI • NCCAM NCCIH
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Professional societies and board certification
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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Most of our best chemotherapy drugs originated from plants
Plant Chemotherapy derivative Pacific Yew (Taxus brevifolia) paclitaxel, docetaxel, albumin‐bound paclitaxel Pink & Red Periwinkle (Catharanthus vincristine and vinblastine, vinorelbine roseus) Chinese “Happy Tree” (Camptotheca camptothecin acuminata) Mayapple (Podophyllum peltatum) teniposide and etoposide
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Curcumin NFKappaB inhibitor Increase P53 expression
Green tea MTOR (serine/threonine kinase) inhibitor; P21 upreg Apoptosis by free radical MOA
Bromelain cysteine proteinases with antimetastatic, antithrombotic antiedematous, fibrolytic,
Quercetin histone deacetylase inhibitor Tyrosine kinase inhibitor
Artemisinin Iron oxidative stress
Ascorbate Oxidative burst in malignant cells
Melatonin Proteosome inhibitor Anti-estrogen Trametes versicolor (Lu and Disis UW TVG Immune modulator via 2011-2012) Toll-like 2 receptor agonist Dectin-1 agonist Inflammasome agonist 6
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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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IV Vitamin C therapy in ovarian cancer? Ma et al 2014 In vitro Depleted (ATM)/adenosine monophosphate–activated protein kinase (AMPK) pathway mTOR) inhibition and cytotoxic death in ovarian cancer cells.
Animal models Parenteral ascorbate + Taxol/Carboplatin synergistically inhibited ovarian cancer in mouse models
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IV vitamin C RCT in women with ovarian cancer
Reduced chemotherapy-associated toxicity in patients with ovarian cancer
Improved PFS? Improved OS?
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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
12 Published by AAAS
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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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From Lise Alschuler ND, FABNO 15
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Green tea epicatechin active in ovarian, breast and colon cancer.
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. 16
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Curcumin
(no copyright) 17
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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 data
Increases 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)
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The adverse side effects of cancer treatment can often be attenuated with oral curcumin.
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Mistletoe lectins
Widely used in Europe –SQ and IV improves QOL in ovarian cancer patients
Mistletoe in vitro and animal data and clinical data (Schumacher, Feldhaus et al. 2000; Piao, Wang et al. 2004)
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Indole‐3‐carbinol
Indole‐3‐carbinol In vitro data showing ovarian cancer sensitization to 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
Selenium Selenium 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 fungi Trametes 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=30 UW/Bastyr/NCCAM partnership (Disis/Salazar/Standish) NCT01922921
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Ferry DR et al Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 1996 Apr;2(4):659-68.
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Quercetin (3,3',4',5,7‐pentahydroxyflavone) 1.Inhibits the growth of tumor cells 2.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 kinase 4.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 drugs in 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, Rahbarghazi et al. 2017)
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Vitamin D 5000 iu/day 45‐70 mg/dl
Vit 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. 35
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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 Supported Chemotherapy (MSCT): A Retrospective Study. JOP. J Pancreas 2016 Jan 08; 17(1):36‐41. Iyikesici et al (2016)
14 hr pre‐chemotherapy water fast Humulin 5 units 20 min before start of chemotherapy infusion Ketogenic diet before and after
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Funding Budge 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 registries 1. 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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Adverse Event Serious Non‐Serious BIORC adverse events (AE) Chills (2) x
Psychiatric Adverse event (AE) data is collected from staff reports. x AE’s are categorized and reported using the NCI‐CTAE Disorder Other Bruising x system.
Respiratory Other x A serious adverse event is an event that results in any of Anemia x the following outcomes: death, life threatening event, Hypoglycemia x
inpatient hospitalization, persistent or significant Pain x disability or incapacity. Vomiting (4) x Dizziness x Data collected since 1/2012 to 10/1/2013. Tracheal obstruction x
24 AE’s reported on 13 patients Hot flashes (2) x
Nausea (3) x
Allergic reaction x
Headache x
Diarrhea x Dyspnea x Cough x
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eribulin Iniparib + carboplatin + Abraxane gemcitabine
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Cost for course of Treatment dosage Frequency Duration treatment ($)
Bromelain 1500 mg daily 365 days 627.80
Curcumin 3000 mg daily 365 days 450.17
Green tea 2000 mg daily 365 days 87.38
IV Artenusate 120 g weekly 12 months 12,064.00
IV ascorbic acid 100 g weekly 12 months 12,064.00
Melatonin 20 mg daily 365 days 24.30
Mistletoe injections 1 injection weekly 12 months 236.85
T. versicolor mushroom 3000 mg 365 days daily 608.33
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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Stage IV ovarian cancer N =12
SEER data
BIORC median survival 2 years SEER median survival 2 years
Ovarian cancer (Stage IV at FOC) 1 year 2 years 3 years Survival Rate 75% 42.9% 32.1%
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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 from Bastyr intake
Rose, P. G., J. J. Java, et al. OS = 4.5 years in stage 1-3 (2016). "Disease extent at secondary cytoreductive surgery is predictive of progression-free and overall survival in advanced stage ovarian OS = 2.0 yr cancer: An NRG Oncology/Gynecologic Rose 2016 Oncology Group study." OS = 3.6 yr Gynecol Oncol 143(3): 511-515.
Work completed by Sherry Su, ND 2016 47
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Bastyr ovarian cancer outcomes (2009‐2016) N =42 consecutively enrolled women with ovarian cancer.
Stage Total at dx
1‐3 33
4 6
Unknown 3
Main outcomes = median PFS and median OS Total 42
Stage Total at FOC
1‐3 27
4 15
Total 42
Work completed by Jinda Chaijinda, ND candidate 2017. 48
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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)
Bastyr median PFS = 24 mo.
Rose et al 2016 N = 555 PFS = 13.8 mo Dittrich, C., P. Sevelda, et al. (2003). "Lack of impact of platinum dose intensity on the outcome of ovarian cancer Dittrich 2003 patients. 10‐year results of a prospective randomised phase III study comparing carboplatin‐cisplatin with PFS = 29.7 mo 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)
50 Thanks to Fred Dowd for all KM curves.
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Median OS in stage 1‐3 from DX = 46 months
Sundar 2012 Rose 2016 Median OS = 30.6 mo Median OS = 43 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 with IV therapy = 26 mo
Median OS = 22 mo without IV
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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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CUSIOS The Canadian/US Integrative Oncology Study
Advanced Integrative Oncology treatment for patients with advanced stage cancer: A prospective outcomes study
Canadian PI: Dugald Seely, ND, MSc, FABNO US PI: Leanna Standish, PhD, ND, FABNO
Research Team: Julie Ennis, Ellen McDonell – OICC/CCNM Linda Dale, Peich Cheng, Fred Dowd - Bastyr
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CUSIOS
(1) Measure survival of late stage breast, colorectal, ovarian and pancreatic cancer patients who receive AIO treatments (2) Describe AIO treatments recommended by naturopathic oncologists for late stage cancer (3) Pilot the collection of health‐related quality of life (HR‐QOL) data on a subset of Canadian AIO treated 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) Coriolus Versicolor –3gm qd Curcumin 4000 mg/day Theracurmin 120mg bid Trametes versicolor 1500 mg bid Quercetin – 500mg bid Bromelain 1500 mg bid LDN –3‐4.5 mg qd Probiotics ORAL Metformin Quercetin 750 mg bid Magnesium 450mg qd Wobenzyme 3 tables QID Vit D –1‐1000iu/day or more dependent on serum vit D Modified citrus pectin 6 grams bid Fish oil – combined 2000mg of EPA/DHA Low dose naltrexone 4.5 mg h.s. Vitamin D3 5000 iu/day IV ascorbate (first line) IV C IV Artenusate IV mistletoe or subQ IV nutrition INJECTABLES IV hydration Vitamin B complex i.m. Mistletoe SQ
TOPICAL Castor oil if tendency to bowel obstruction or constipation Castor oil pack Hyperthermia PHYSICAL MEDICINE Acupuncture Hyperbaric oxygen Sauna/sweat Dependent on capacity 20‐40 mins moderate to vigorous ECOG 0 ‐ 20 min aerobic daily EXERCISE activity daily ECOG 1‐2 ‐ 20 min walking daily Qi gong class Yoga Yoga class Meditation MIND‐BODY MBMSR Nature walks HeartMath biofeedback retreats 58
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CUSIOS Clinical Sites
Canadian Sites C1 Ottowa Integrative Cancer Center (OICC) Dr. Seely Ottawa, ON C2 Vital Victoria Naturopathic Clinic Ltd (VVNC) Dr. McKinney Victoria, BC C3 Integrated Health Clinic Cancer Care Centre Fort Langley, Dr. Parmar (IHCCC) BC C4 Marsden Centre for Excellence in Integrative Dr. Marsden Vaughan, ON Medicine (MCEIM) C5 HealthSource Integrative Medical Centre Dr. Reid Kitchener, ON (HSIMC)
American Sites U1 Shelby Naturopathy, PLLC (SNP) Dr. Standish Seattle, WA U2 Naturopathic Specialists, LLC (NSL) Dr. Rubin Scotsdale, AZ U3 Salish Cancer Center (SCC) Dr. Reilly Fife, WA U4 Lokahi Health Center (LHC) Dr. Traub Kailua Kona, HI U5 Woodinville, Tree of Health Integrative Medicine (THIM) Dr. Naydis WA U6 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
Cancer Type Distribution
Participants: The study sample size is 400 advanced stage cancer patients: 21, 13% Breast • 150 with stage 4 breast 65, 40% 30, 19% Colorectal • 150 with stage 4 colorectal Pancreatic • 50 with stage 3 or 4 ovarian Ovarian • 50 with stage 3 or 4 pancreatic 46, 28%
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N = 400 50 with stage 3 or 4 ovarian cancer
CUSIOS Recruitment 500 400 300 200 100 0 Jul Jul -100 Jul Oct Oct Oct Apr Apr Apr Jun Jun Jan Jun Jan Jan Feb Mar Feb Mar Feb Mar Participants Aug Sep Nov Dec Aug Sep Nov Dec Aug Sep Nov Dec May May May 2015 2016 2017 2018 Months 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 Center Seattle, WA
RESTART PRINCIPAL INVESTIGATOR M. Robyn Andersen, PhD
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Targeted natural medicine cancer treatment pathways
Adapted from Lutendorf 2011 and modified by Peih Chiang, ND.
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Can shift to heart rate coherence affect the tumor 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 Team
PRINCIPAL 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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425‐602‐3166
See appendix for CAM symptom management therapies.
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Thank you.
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Table XX. Advanced integrative oncology treatment for symptom management Integrative oncology
symptom management in ovarian cancer
Symptom or side CCNM Bastyr effects Anorexia Whey protein, IV nutrition melatonin, fish oil
Abdominal pain Acupuncture Castor oil pack Castor oil pack acupuncture Massage
anemia B complex – oral Vitamin B complex im weekly Marrow Plus TCM formula leukopenia Astragalus Acupuncture Mistletoe subQ Trametes versicolor Coriolus Withania
Bone pain Acupuncture Claritin Benadryl Ibuprofen Curcumin Symphytum homeopathic Eupatorium homeopathic
dyspnea Acupuncture Nebulized GSH +NAC Yoga Bromelain Breath work quercetin hypnotherapy
diarrhea Acupuncture Tincture of opium 73
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Depression Fish oil –high EPA/DHA (3:1) 2000mg Citalopram Pascoeflair qd St John wort Counseling B complex Yoga psychotherapy Exercise
Anxiety Neurapas qd Citalopram GABA Meditation training Hypnotherapy Rescue Remedy Counseling Massage Nature walks Exercise
Dyspareunia Replens 1 mg estriol vag suppository Estrogen cream suppository
Apthous ulcers (stomatitis) L‐glutamine l‐glutamine Coconut oil vit E topically Viscous lidocaine
GERD DGL DGL chewables Melatonin Food hygiene (chewing, mixing foods) Reduce anxiety
gastritis DGL DGL chewables Digestive enzymes Mediclear
hypoalbuminemia Whey protein IV aminosyn ascites Acupuncture Bromelain Wobenzyme 74
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Pleural effusion Bromelain Wobenzyme osteoporosis ProBones (mix of minerals) Osteoprime formula Cal/Mag Vit D
insomnia Melatonin Melatonin L‐theanine 5‐HTP Passionflower neurapas Sleep hygiene – reading, no phone or tv Ileus ER acupuncture Nausea and vomiting Ginger tea or tabs Ginger tea Nux vomica homeopathic
Cerebral edema Boswellia – 1500mg qd Boswellia 3000 mg/day
Ankle edema Acupuncture Wobenzyme Whey protein Vit C + bioflavanoids Peripheral neuropathy Acupuncture l‐glutamine ALA IV GSH Benfotiamine Liposomal GSH Elevated blood sugar Berberine Metformin ALA Diabetone Metformin Nerve pain Acupuncture Hypericum homeopathic Epsom salt baths
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‘chemo brain’ Gingko Biloba Acetyl‐carnitine (Memoractive) Melatonin Acetyl L‐carnitine
lymphedema Acupuncture Wobenzyme Proteolytic enzymes Physical therapy by lymphatic Lymphatic drainage Expert Apis homeopathic
Hot flashes Estrovera (Siberian rhubarb) SJW + remifemin (black cohosh) Remifemin citalopram Soy Sage Acupuncture
Constipation Magnesisum glycinate Triple magnesium Hand and foot erythema Hand to Heal cream Vitamin B6 50‐150 mg/day in am with food B‐complex
Nose bleeds Remove/reduce curcumin Hawthorne berry extract ½ tsp bid Vit C + bioflavanoids
Cardiotoxicity and poor ejection fraction CoQ10 coQ10 100 mg/day L‐carnitine Hawthorne Berry ½ tsp bid
Generalized pruritus Oatmeal filtered baths quercetin
Arthralgia & myalgia Acupuncture Curcumin Curcumin Magnesium Fish oil Epson salts bath CoQ10 Acupuncture
Thrombocytopenia Sesame oil – 2 Tbsp oral or topical Sesame oil 2 tablespoon oral or topical
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