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Probiotics

Probiotics Relieve Chemotherapy Related Diarrhea and Oral Mucositis

Chemotherapy can lead to serious diarrhea and oral mucositis in cancer patients.  This may affect the ability of a patient to complete their course of chemotherapy and to maintain proper hydration, electrolyte balance and nutritional status.  Interruptions or changes to their therapeutic course of treatment may subsequently affect patient prognosis and overall survival.  Skillfully managing these adverse effects is crucial to successful outcomes, nutritional status and health.

A systematic review and meta-analysis on the efficacy of oral probiotics in the management of adverse reactions to chemotherapy examined twelve trials, including 1013 patients.

An analysis of the 12 studies reviewed revealed that patients who took oral probiotics had significant decreases in diarrhea and oral mucositis.

“In contrast to the control group, orally taking probiotics significantly decreased the risk of chemotherapy-induced diarrhea (≥ 1 grade) (RR = 0.70; 95% Cl: 0.56, 0.88; P = 0.002) and oral mucositis (≥ 1 grade) (RR: 0.84; 95% Cl: 0.78, 0.91; P < 0.00001) at all grades. Further analysis found that severe diarrhea (≥ 2 grades) (RR: 0.50; 95% Cl: 0.32, 0.78; P = 0.002) and severe oral mucositis also significantly declined (≥ 3 grades) (RR: 0.66; 95% Cl: 0.55, 0.79; P < 0.00001) after oral probiotic use.”

Of note, patients taking muti-species oral probiotics had a decrease in adverse effects compared to patients taking single or dual-strain formulations.

More recent studies have also demonstrated that patients who have a healthier intestinal microbiome also have an improved therapeutic and immune response to both chemotherapy and immunotherapy treatments. 

A healthy microbiome is part of our systemic immune response and systemic inflammation control.

I recommend the use of high-quality multi-strain probiotic supplements in all of my patients.

It is also important to use prebiotics simultaneously as it is the prebiotics that provide the short-chain fatty acids, the fuel of the healthy microbiota, and allow the healthy bacteria to flourish and colonize. 

Prebiotics are also important to successfully supporting the intestinal microbiome. There are combination supplements that contain both probiotics and prebiotics that provide both elements.

A plant-strong diet will provide plenty of soluble fibers that are fermented in the gut and provide the short-chain fatty acids essential to a healthy and robust microbiome.   These foods are excellent sources of insoluble fiber: Jerusalem artichokes, chicory, onions, leek, shallots, asparagus, beetroot, fennel, peas, cabbage, nuts and seeds and cabbage family vegetables including kale, broccoli, cauliflower, cabbage, bok choy, Brussels sprouts for example. 

In contrast, insoluble fibers such as bran and cellulose found in grains and vegetables are not digested or fermented and primarily provide bulk and roughage important to intestinal tone and normal stool.)

Healthy probiotic bacteria can be found in traditional natural fermented foods from many cultures worldwide.

I recommend a teaspoon of a variety of fermented vegetables daily, such as sauerkraut, kim chi or fermented beets or carrots, for a broad spectrum of food-based probiotics.  For patients who are not sensitive to dairy products, yogurt, kefir and soft goat and sheep cheese are also healthy sources of probiotics in the diet. 

For patients experiencing diarrhea and mucositis, I recommend a diet of only warm, cooked food, restricting ice, cold foods and raw foods.  I also recommend 2-4 cups of bone broth daily, which is rich in collagen protein and glutamine for repair as well as a good source of electrolyte replacement for a patient with diarrhea.  One cup of traditionally prepared bone broth, which can be found in many natural foods stores and online, contains 10g of protein per cup.  A patient drinking 4 cups daily will gain 40g of protein, important to the nutritional repletion of cancer patients who are also at risk for sarcopenia.

Probiotics, healthy commensal and symbiotic gut bacteria, and prebiotic soluble fibers from plant foods should be part of a therapeutic approach to adverse effects of chemotherapy but also part of a healthy daily diet to maintain robust microbiota in the intestines, so crucial to long-term health and wellbeing.

Selected References

Feng J, Gao M, Zhao C, Yang J, Gao H, Lu X, Ju R, Zhang X, Zhang Y. Oral Administration of Probiotics Reduces Chemotherapy-Induced Diarrhea and Oral Mucositis: A Systematic Review and Meta-Analysis. Front Nutr. 2022 Feb 28;9:823288. doi: 10.3389/fnut.2022.823288. PMID: 35299763; PMCID: PMC8922230.

Sevcikova A, Izoldova N, Stevurkova V, Kasperova B, Chovanec M, Ciernikova S, Mego M. The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy. Int J Mol Sci. 2022 Jan 1;23(1):488. doi: 10.3390/ijms23010488. PMID: 35008915; PMCID: PMC8745082.

Guo C, Kong L, Xiao L, Liu K, Cui H, Xin Q, Gu X, Jiang C, Wu J. The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies. Cell Biosci. 2023 Oct 13;13(1):188. doi: 10.1186/s13578-023-01135-y. PMID: 37828613; PMCID: PMC10571290.

Matson V, Chervin CS, Gajewski TF. Cancer and the Microbiome-Influence of the Commensal Microbiota on Cancer, Immune Responses, and Immunotherapy. Gastroenterology. 2021 Jan;160(2):600-613. doi: 10.1053/j.gastro.2020.11.041. Epub 2020 Nov 28. PMID: 33253684; PMCID: PMC8409239.

Is It Safe to Use Chinese Mushrooms with Cytotoxic Chemotherapy Drugs?

According to surveys in the United States, Canada and Europe an average of 35% of cancer patients use Chinese Herbal Medicine during their cancer treatments.  Among Asian patients the use of Chinese Herbs is even higher.  There are always the questions of both safety as well as drug-herb interactions when patients use herbal medicines concurrently with cytotoxic chemotherapy treatments.

Two of the most widely studied Chinese medicinal mushrooms are Reishi or LingZhi (Ganoderma lucidum, Ganoderma chinense) and YunZhi or Turkey Tail Mushroom (Trametes versicolor, Coriolus versicolor).  These are widely used as adjunctive medicinal foods by cancer patients and as therapeutic agents in both traditional and Modern Chinese Medicine.  These mushrooms are considered Immune Modulators having an epigenetic impact on the expression of tumor promoter and tumor suppressor genes.  Additionally, they act as Immune System Activators influencing both innate and adaptive functions of the immune system, influencing the activity of T cells, natural killer cells and neutrophils and have antiviral and antioxidant properties. Chinese Mushrooms positively impact glycemic control as well as supporting the health and balance of the intestinal microbiome.  Traditionally and historically Chinese Mushrooms have been considered to Enhance Overall Health and Vitality, Promote Longevity and Support Cognitive Clarity and Meditation.

In a systematic review by Lam, et al, of 213 studies, including 77 human studies both Reishi Mushroom and Turkey Tail Mushroom were found to be safe when used concurrently with chemotherapy.  In some studies, a synergistic effect and enhancement of tumor cell cytotoxicity and clinical efficacy of the chemotherapy drugs was observed.  There was a general decrease in common adverse effects such as fatigue, gastrointestinal discomfort, nausea, vomiting, diarrhea, constipation. Peripheral neuropathy and hand-foot syndrome were also reduced.

It was noted that PSP, a derivative of YunZhi, did show interactions with cyclophosphamide, potentially increasing the cytotoxic effects.   Overall undesirable drug-herb interactions were not reported.  Further studies to expand knowledge of pharmacokinetics of medicinal mushrooms is required to understand their mechanisms of action more deeply.

Patients who used these mushrooms while undergoing chemotherapy treatment with a wide range of cytotoxic chemotherapy drugs showed improved quality of life, improved survival, and improved response to treatment.  Patients also experienced less side effects and support for maintenance of normal immune function.

I generally do include Chinese Medicinal Mushrooms, including Reishi and Turkey Tail as therapeutic concentrated foods.   Hot water extracts of both fruiting body and mycelia are recommended.   Companies that product mushrooms on a natural medium yield the most active therapeutic constituents.  I do not recommend mushroom products grown on grain or products that contain only mycelia.  While these are cheaper, they are of poor quality and do not have the extraordinary life-giving properties of traditionally produced mushrooms.

I recommend 3-6 grams daily of properly prepared high quality mushroom powders as a therapeutic dose and 2-3 grams daily for healthy individuals as a nutritional dose.

Powerful immune enhancing agents are contraindicated in patients with auto-immune inflammatory syndromes, patients receiving immunotherapy with PD1, PDL1 and Checkpoint inhibitors and transplant patients on immunosuppressive therapies.  Additionally use caution with patients diagnosed with leukemias and lymphomas.

Selected References

  1. Lam CS, Cheng LP, Zhou LM, Cheung YT, Zuo Z. Herb-drug interactions between the medicinal mushrooms Lingzhi and Yunzhi and cytotoxic anticancer drugs: a systematic review. Chin Med. 2020 Jul 25;15:75. doi: 10.1186/s13020-020-00356-4. PMID: 32724333; PMCID: PMC7382813.

  2. Carmady B, Smith CA. Use of Chinese medicine by cancer patients: a review of surveys. Chin Med. 2011;6:22.

  3. Lam Y, Cheng C, Peng H, Law C, Huang X, Bian Z. Cancer patients’ attitudes towards Chinese medicine: a Hong Kong survey. Chin Med. 2009;4:25.

  4. Yeh Y, Chou Y, Huang N, Pu C, Chou P. The trends of utilization in traditional Chinese medicine in Taiwan from 2000 to 2010: a population based study. Medicine (Baltimore). 2016;95(27):e4115.

  5. Yuen JW, Gohel MD Anticancer effects of Ganoderma lucidum: a review of scientific evidence. Nutr Cancer. 2005;53(1):11-7. DOI 10.1207/s15327914nc5301_2.PMID: 16351502 

People exercising

Reduced Mortality in Cancer Survivors Who Exercise

Exercise is Medicine

In order to be a Survivor-Thriver and significantly reduce risk of recurrence, cancer patients must be encouraged to develop a life-long habit of regular exercise with clear guidelines, measurable goals and behaviors and coaching support if necessary to successfully integrate a new habit. Exercise has the potential to reduce all cause mortality in cancer survivors by 25%.

According to investigator, Lee W. Jones, PhD, of Memorial Sloan Kettering Cancer Center in New York City, in a study involving 11,480 survivors, with 16 year median follow up, patients who followed exercise guidelines enjoyed a 25% reduced risk of all-cause mortality compared with patients who did no exercise (HR 0.75, 95% CI 0.70-0.80).   [1]

Additionally, patients who followed exercise guidelines also showed a significant reduction in cancer mortality (HR 0.79, 95% CI 0.72-0.88), as well as mortality from other causes (HR 0.72, 95% CI 0.66-0.78).[1]

Exercise was associated with a reduction in all cause mortality (for breast, endometrial, head and neck, hematopoietic, prostate, and renal cancers), cancer-specific mortality (for head and neck, and renal cancers), and other cause mortality (for breast, colon, endometrial, hematopoietic, and prostate cancers).

In patients who adopt an active lifestyle and follow exercise guidelines, the benefits may last for two decades after diagnosis.  [2]  Meeting versus not meeting the exercise guidelines was associated with a 25% reduced risk of all-cause mortality, a 21% reduced risk of cancer mortality, and a 28% reduced risk of death from other causes. [2]  

“Compared with no exercise, there were statistically significant reductions in cancer-specific mortality among those exercising below the exercise guidelines and larger reductions for those meeting and exceeding the guidelines, 19%, 25%, and 33% reductions, respectively, which demonstrates that all levels of exercise are beneficial.” [2]

“The American Cancer Society guidelines recommend that physical activity assessment and counseling begin as soon as possible after diagnosis, to help patients prepare, tolerate, and respond to treatments, and manage symptoms and treatment side effects.” [3]

Exercise Guidelines in the study included moderate-intensity exercise 4 or more days per week, with each session, on average, 30 or more minutes in duration and/or strenuous-intensity exercise 2 or more days per week, with each session, on average, 20 or more minutes in duration.

On the very first patient visit I talk about the value and importance of exercise and include an exercise prescription in every patient’s care plan from day one.   I ask patients to accumulate 60 minutes of movement activity daily.  They can start with 10 or 15 minute sessions until they build up more fitness, strength and stamina.  

Unfortunately, only 38% of cancer patients in the study were classified as “exercisers”.    Some cancer patients think, mistakenly, that they should rest and convalesce and that exercise may do harm.  On the contrary, patients undergoing all types of treatments and those in remission and in recovery benefit from some type of appropriate movement.  Of course, each patient should be assessed individually and given appropriate guidelines, training and supervision.   Using apps that track activity can increase interest and compliance.

The reality is that the awareness of the positive impact of exercise is very low among cancer patients and cancer survivors.  Exercise is truly one of the “big levers”, a source of significant impact upon the health, well-being, mood, sleep, bone density, muscle mass, prognosis, quality of life and SURVIVAL of cancer patients.  

I envision all cancer treatment centers having an exercise room at their facility!!!

I propose a new specialty “Exercise Oncology”!  

The OutSmart Cancer System is a HEALTH MODEL.  Every patient receives exercise guidelines, support and coaching to develop and sustain lifestyle and self care habits that create a body where cancer cannot thrive.

Selected References

  1. Jessica Lavery, Lee Jones et al
    Pan-Cancer Analysis of Postdiagnosis Exercise and Mortality
    DOI: 10.1200/JCO.23.00058 Journal of Clinical Oncology  PMID: 37651670

  2.  Stacey Kentfield, June Chan
    Meeting Exercise Recommendations Is Beneficial for Cancer Survivors
    DOI: 10.1200/JCO.23.01528 Journal of Clinical Oncology
    Published online September 20, 2023. PMID: 37729601

  3. Rock CL, Thomson CA, Sullivan KR, et al:
    American Cancer Society nutrition and physical activity guideline for cancer survivors.
    CA Cancer  J Clin 72:230-262, 2022
anxiety-and-depression

Integrative Resources for Cancer-related Anxiety and Depression

The OutSmart Cancer® System is a WHOLE PERSON approach to supporting the health of cancer patients, survivors and their loved ones.  This includes addressing the psycho-social and spiritual needs of our patients.

Anxiety and depression are common human responses both for patients and loved ones  during every phase of the cancer journey, from diagnosis, active treatment, recovery, living with cancer as a chronic illness or as a cancer survivor long term.  Psychological and spiritual concerns often go untreated.

Most patients require some encouragement to talk about their emotional, psychological and spiritual challenges. It is vital to include thoughtful support and resources to all patients, family members and significant others

ASCO

Cancer is a collective experience and everyone close to the patient is touched by the diagnosis and the suffering.   Everyone is transformed by the depth and intensity of the experience.

“I very much like to frame the cancer journey as an opportunity, as a meaningful and sacred gateway in

 one’s life.  It is a time for reflection and inquiry and for clarifying one’s priorities and core values.  

Many patients and families find the depth and intimate nature of the experience to be ultimately transformational and healing, especially when shared.”

I ask  patients to ponder the questions:

  • What gives me strength?
  • What gives me courage?
  • What are my fears?
  • What are my hopes and dreams?

Patients and families are encouraged to take the opportunity to enter into a new phase of life with new learned self-care and lifestyle tools and resources in alignment with the health focused and proactive principles of my OutSmart Cancer® System.

patients-and-families

The Society for Integrative Oncology(SIO) and ASCO (The American Society of Clinical Oncology) have co-published a resource outlining an integrative approach and research supported resources and recommendations for patients during active treatment as well as post-treatment.

“ I think of post-treatment as the rest of your life, not a finite period of time.”

Recommended Interventions from SIO and ASCO include:

  • Mindfulness based interventions/meditation
  • Yoga
  • Tai Chi/Chi Gung
  • Hypnosis
  • Acupuncture
  • Music/Music Therapy
  • Reflexology (Massage)
  • Aromatherapy: Lavender Essential Oil

SIO and ASCO convened a multi-faceted and diverse expert panel. Their literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2023. This team developed evidence-based guideline recommendations. The literature search identified 110 relevant studies (30 systematic reviews and 80 randomized controlled trials) to inform their guidelines.

I also encourage patients to seek appropriate psychological and spiritual counseling, spend time in nature, engage in creative activities  through art, dance, movement, writing, journaling and poetry as well as the recommendations outlined above.

It is possible to transform challenges and suffering into the pearls of new insights, loving-kindness, compassion and wisdom that can richly inform our inner and outer lives at every phase of the cancer journey.

Additional information is available at www.asco.org/survivorship-guidelines

Reference:

Integrative Oncology Care of Symptoms of Anxiety and Depression in Adults With Cancer: Society for Integrative Oncology–ASCO Guideline

Linda E. Carlson, Nofisat Ismaila, Elizabeth L. Addington, et al

Rhodiola

Rhodiola, Mitochondria and Cancer Chemoprevention

Rhodiola (rosea and crenulata spp.) is a botanical adaptogen with broad application in cancer chemoprevention and mitochondrial support for cancer patients undergoing and recovering from cancer therapies.

Rhodiola is considered an adaptogen. It supports multiple functions that enhance resilience, responsiveness and recovery in the face of stress.

mitochondriaRhodiola came to widespread prominence when it was used by Olympic athletes, high altitude mountain climbers and long distance runners to enhance endurance and sustained energy over 50 years ago.

Rhodiola rosea and its primary active phytochemicals, salidroside and rosavins, have been widely studied for effects on cellular metabolism, energy production, inflammation control, oxidative stress, autophagy and cell death.

Salidroside is known to bind to the cell membrane and enter the cytosol via a membrane transporter where it influences AMPK and improves endothelial function and nitric oxide production, enhances glucose uptake and fatty acid oxidation and inhibit and gluconeogenesis and glycogen synthesis.

AMPK activity is required for cells to respond to stress and changes in energy balance.  It is primarily through this pathway that Rhodiola appears to enhance normal mitochondrial function and energy metabolism.  

Salidroside is water soluble and highly bioavailable via oral administration and its metabolites are excreted in the urine.

Rhodiola has also been shown to inhibit tumor promoting mTOR pathway and reduce angiogenesis and metastasis by down-regulating expression of HIF1a/HIF2a signaling. Reducint mTOR expression is a goal in chemoprevention and in optimizing the tumor microenvironment.

Rhodiola has demonstrated positive synergistic effects when combined with the chemotherapy agent cyclophosphamide.  

Rhodiola metabolites are excreted through the urine and one human study showed that patients with superficial bladder carcinoma who consumed Rhodiola orally reduced the average frequency of recurrence by 50%. 

Murine studies have shown that Rhodiola has Immuno-stimulating properties and increases, CD3 and CD4 T cells, Interferon-g and IL-2 cytokines.

Rhodiola demonstrates anti-inflammatory activity by inhibition of COX2, PLA2, NfkB, TNFa, IL-1B and IL-6 which are all upregulated in the tumor microenvironment. Additionally Rhodiola has inhibits expression of the NLRP3 inflammasome which is activated in the lung epithelia both during viral infections as well as malignancy.  (As a side note, this property of Rhodiola may also enhance vaccine adjuvant effect and maturation of dendritic cells and promote immune response to vaccine innoculation)

rhoRhodiola rosea and Rhodiola crenulata  are available as liquid botanical extract and in capsule form. Rhodiola extracts typically contain 3% salidrosides and 1% rosavins.  A therapeutic dose of Rhodiola is 3000mg/day.

A maintenance dose for cell protection and healthy aging ranges from 200-1000mg per day. Always use professional grade supplements and suppliers.

Rhodiola has a wide range of applications in chronic syndromes, healthy aging, and chemo-prevention and recovery by positively influencing multiple pathways in the cancer terrain and tumor microenvironment.

Selected References

Rhodiola and salidroside in the treatment

of metabolic disorders                                               
Xiang-Li Bai, et al, DOI : 10.2174/1389557519666190903115424

Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention

Yonghong Li , et al DOI: 10.1007/s40495-017-0106-1

mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management                            
Silvia Cetrullo
, et al DOI: 10.1615/critreveukaryotgeneexpr.2015012975 

Cancer-SARS

Inflammation, Cancer and SARS-CoV2

Managing Inflammation and Inflammasome in both the Cancer Terrain and SARS-Cov2

There is a subset of cancer patients who suffer significantly more inflammation as well as the sequela of increased inflammation including ongoing cancer related fatigue, increased pain, cognitive deficits.   Similarly there is a subset of COVID-19 patients who suffer a cytokine storm and the wildfire of inflammation that leads to respiratory distress syndrome and mortality. Identifying patients with a higher risk of increased inflammation can be assessed by taking a thorough history in search of historical tendencies and patterns and an analysis of single nucleotide polymorphisms (SNPs).  Patients with IL1B, IL6 and NFkB  SNPs are more prone to developing greater inflammation in both syndromes.

inflammationThe inflammatory drivers and cytokines are similar in both cases: NFkB, TNFa, IL1, IL6, IL8, Inflammasone NLRP3, TGFb1, STAT3, JAK2, p38MAPK, Nrf2, AMPK

Activation of Inflammasome NLRP3 is correlated with the development of the SARS CoV2 cytokine storm.  Inflammasome activation is an important component of innate immunity which enhances inflammation.  Inflammasome activity is correlated with destructive inflammation particularly in viral diseases.  Inflammsome NLRP3  increases IL-1B is also  upregulated in the cancer terrain, particularly in metastatic lung cancer, breast cancer, fibrosarcoma and gastric carcinoma.

curcuminCurcumin exhibits anti-inflammatory and anti-inflammasome properties and can be used in both syndromes.  Curcumin impacts all of the above named inflammatory drivers along with inhibition of COX2 transcription.    Furthermore curcumin acts as an antioxidant increasing control of reactive oxygen species present with increased inflammation.

I recommend Designs for Health Curcumevail, Thorne Research Meriva and Euromedica Curapro.  In managing both the cancer terrain and the SARS CoV2 terrain the dose range is 2g-6g curcuminoids per day.

Another actor, Nrf2, is a nuclear transcription factor that increases the presence of antioxidant proteins when cells are stressed.   Management of the cancer terrain also includes support for normal function of Nrf2.  Nrf2 is highly expressed in the lungs and is responsible for inhibiting the activity of Inflammasome NLRP3.  Sulforaphanes include Di-indole methane, Indole-3-Carbinol and  Sulforaphane glucosinolate.  Broccoli, broccoli sprouts and kale are dietary sources of sulforaphanes.  

antioxidant

I recommend Designs for Health Broccoprotect and Thorne Research Crucera for a high quality source of sulforaphane glucosinolate 50mg twice daily.

Ultimately we may find that the core foundation and targeted supplements used in the OutSmart Cancer System for managing the cancer terrain ALSO protect our patients in the midst of a viral pandemic.

Selected References 

Rajendra Karki et al Inflammasomes and Cancer                                                                                                             PMID: 28093447 DOI: 10.1158/2326-6066.CIR-16-0269

Saeedi‐Boroujeni  et al COVID‐19: A Case for Inhibiting NLRP3 Inflammasome, Suppression of Inflammation with Curcumin?  Ali  https://doi.org/10.1111/bcpt.13503 Volume128, Issue1 January 2021 Pages 37-45

Howrylak JA, Nakahira K. 

Inflammasomes: Key Mediators of Lung Immunity. 

Annu Rev Physiol. 2017;79:471‐494. doi:10.1146/annurev-physiol-021115-105229

James W.Pinkertona1Richard Y.Kima1Avril A.B.RobertsonbJeremy A.HirotacLisa G.WoodaDarryl A.KnightaMatthew A.CooperbLuke A.J.O’NeilldJay C.Horvata1Philip M.Hansbroa  Inflammasomes in the Lung

Molecular Immunology Volume 86, June 2017, Pages 44-55         

Shih-Yi Chuang,1,2 Chih-Hung Lin,3,4 and Jia-You Fang

Natural Compounds and Aging: Between Autophagy and Inflammasome

Biomed Research Int. Volume 2014 |Article ID 297293 | 10 pages | https://doi.org/10.1155/2014/297293                                                    

József Tőzsér1 and Szilvia Benkő

Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production

Mediators of Inflammation Volume 2016 |Article ID 5460302 | 16 pages                                               https://doi.org/10.1155/2016/5460302

turmeric

Tumeric Prevents Chemotherapy Induced Hand Foot Syndrome

Xeloda (Capecitabine) is the oral form of  chemotherapy agent 5-Fluorouracil  (5-FU) which is administered intravenously. 

Both drugs are widely used in a broad range of cancers. The mechanism of action is inhibition of mitosis (cell division).   

One of the most common side effects of these drugs is HAND-FOOT SYNDROME or palmar-plantar erythrodysesthesia.  Hand-Foot syndrome presents with redness, swelling and pain, tingling, burning and sensitivity to touch on the palms of the hands and the soles of the feet. Severe cases may include cracked, flaking or peeling skin, painful blisters, ulcers or sores, severe pain and difficulty walking or using the hands.

While etiology is not certain it is hypothesized that these drugs cause capillary fragility and subsequent leakage of drugs into and damage of  the surrounding tissue.

fhs

Other commonly used chemotherapy agents  which result in Hand - Foot syndrome include 5-Fluorouracil, Capecitabine, Cytarabine, Docetaxel, Doxorubicin, Doxil and Paclitaxel. These drugs are widely used in Breast, Ovarian and Gastrointestinal Cancers.  

Not all patients who receive these drugs develop Hand-Foot Syndrome. The symptoms typically appear with the first dose administration in 40-50 percent of patients at grade 2 or higher.

turmeric-as-cure

Grade 1: painless erythema or dysesthesia, no impairment

Grade 2: painful erythema, swelling, tingling, numbness, dryness, cracking, Desquamation, activity is impaired

Grade 3: strong pain, ulceration, blistering, erythema, limited self-sufficiency

For drugs administered via IV infusion, cold (Ice) gloves and booties that constrict capillaries reduce local exposures in the hands and feet and must be worn during infusions and for several therapy to hands and feet concurrently with chemotherapy infusions. 

Capcetabine increases COX-2 expression in both tumors and healthy tissues.

A double blind placebo controlled study in which oral COX2 inhibitor celecoxib was administered to patients over a 2 year period while receiving capecitabine or capecitabine plus oxaliplatin demonstrated a significant decrease in the incidence and intensity of symptoms.

The phytochemical curcumin derived from Rhizoma Curcuma longa interacts with over 100 genes that impact tumor cell behavior and metabolism. Curcumin is known to decrease COX2 expression along with expression of  pro-inflammatory NFkB, TNFa, IL1B, IL6 and IL8.  

foot-hand-syndromeIn a human study researchers administered turmeric at a dose of 4 g/day (2 pills 12 hours apart) starting at the beginning of capecitabine treatment and lasting six weeks. The study included 40 patients whose mean age was 62 years. Most were female (80%), 52% had breast cancer, and 47.5% had GI tumors. After the first cycle of capecitabine treatment, 11 of 40 patients developed HFS (27.5%; 95% CI [15, 42]), whereas four patients developed HFS equal or superior to grade 2 (10%; 95% CI [3.3, 23]).. The study concluded that  turmeric combined with capecitabine seems to produce a lower rate of HFS, especially grade 2 or higher. 

Comments

  • There were no contra-indications to utilizing turmeric concurrently with capecitabine
  • A significant therapeutic dose of 4 grams per day was used.   In my practice I prefer to use the more concentrated isolate curcumin and dose at 2-4 grams per day.  This would yield more inflammation control.   
  • Turmeric falls into the category of herbs that “Move Stagnant Blood” in Chinese Medicine.  One of the properties of curcumin is inhibition of platelet aggregation.

References:

Curcuma longa (Turmeric) for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Pilot Study

Vanessa Armenio Scontre , MD,Janine Capobiango Martins , MD, et al 

Jnl Diet Supp Pages 606-612 | Published online: 02 Nov 2017

 https://doi.org/10.1080/19390211.2017.1366387 PMID: 2909565

The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study.Zhang RX, Wu XJ, Lu SX, Pan ZZ, Wan DS, Chen G.
J Cancer Res Clin Oncol. 2011 Jun;137(6):953-7. doi: 10.1007/s00432-010-0958-9. Epub 2010 Nov 27.
PMID: 21113620 Clinical Trial.

stress-cancer

Does Stress Cause Cancer?

 

Lifestyle Factors That Impact Breast Cancer Risk

cancer-and-stress

  • Alcohol:  Drinking Alcohol Increases Risk of Breast Cancer
  • Weight and Body Composition: Excess body fat increases risk for post-menopausal breast cancer. Lean muscle, low body fat decreases risk of pre-menopausal breast cancers
  • Physical Activity: Sedentary behavior is linked to increased risk of breast cancer, while being active decreases the risk of breast cancer 

Vigorous activity decreases the risk for pre-menopausal breast cancer.

Moderate activity decreases risk for post-menopausal breast cancer.

Some evidence indicates that people who are physically active (both before and after diagnosis) have a greater chance of surviving breast cancer.

  • Breastfeeding: Reduces risk of both pre- and post-menopausal breast cancer
  • Sleep: Women who report sleeping less than 5 hours per night  before diagnosis have an increased risk of dying from breast cancer compared to women whose  pre-diagnosis sleep pattern was 7-8 hours per night.  Women who have disrupted circadian rhythms due to night shift work have an increased risk of breast cancer.

cancer-cells

Does Stress Cause Cancer?

Maladaptive and ongoing responses to stress mediated by the Autonomic Nervous System and Hypothalamic Pituitary Axis promote a tumor microenvironment that favors inflammation, oxidative stress, poor glycemic control, carcinogenesis, proliferation, angiogenesis and metastasis

Physiological Pathways, Bio-behavioural Processes and Oncogenesis:

  • Environmental and social processes activate interpretive processes in the central nervous system (CNS) that can subsequently trigger fight-or-flight stress responses in the autonomic nervous system (ANS) or defeat/withdrawal responses through the activation of the hypothalamic–pituitary–adrenal axis (HPA)
  • Individual differences in perception and evaluation of external events (coping) creates variability in individual ANS and HPA activity levels.
  • Over long periods of time, these neuroendocrine dynamics can alter various physiological processes involved in tumorigenesis, including oxidative metabolism, DNA repair, oncogene expression by viruses and somatic cells, and production of growth factors and other regulators of cell growth.
  • Once a tumour is initiated, neuroendocrine factors can also regulate the activity of proteases, angiogenic factors, chemokines and adhesion molecules involved in invasion, metastasis and other aspects of tumour progression.
  • CNS processes can also shape behavioural processes that govern cancer risk (for example, smoking, transmission of oncogenic viruses or exposure to genotoxic compounds).


Integrated Model of Bio-behavioral Influences on Cancer Pathogenesis Through Neuro-Endocrine Pathways

chart

In this model, bio-behavioural factors such as life stress, psychological processes and health behaviours (blue panel) influence tumour-related processes (green panel) through the neuroendocrine regulation of hormones, including adrenaline, noradrenaline and glucocorticoids (red panel). 

Central control of peripheral endocrine function also allows social, environmental and behavioural processes to interact with biological risk factors such as genetic background, carcinogens and viral infections to systemically modulate malignant potential (red panel). 

Direct pathways of influence include effects of catecholamines and glucocorticoids on tumour-cell expression of genes that control cell proliferation, invasion, angiogenesis, metastasis and immune evasion (green panel). 

Stress-responsive neuroendocrine mediators can also influence malignant potential indirectly through their effects on oncogenic viruses and the cellular immune system (red panel). 

These pleiotropic hormonal influences induce a mutually reinforcing system of cellular signals that collectively support the initiation and progression of malignant cell growth (green panel). 

Furthermore, neuroendocrine deregulation can influence the response to conventional therapies such as surgery, chemotherapy and immunotherapy (green panel). 

In addition to explaining bio-behavioural risk factors for cancer, this model suggests novel targets for pharmacological or behavioural intervention. 

(CTL, cytotoxic T lymphocytes; IL, interleukin; MRD, minimal residual disease; NKC, natural killer cell; TGFβ, transforming growth factor-β; TNFα, tumour-necrosis factor-α; TSH, thyroid-stimulating hormone.)

Dr. Nalini’s Adrenal Stress-Immune Support Protocol 

DAYTIME

Designs for Health Adrenotone   2/3x/day. With meals

All-in-one synergistic adrenal support formula. 

Metagenics Immucore 1/3x/day. With meals

Multidimensional Support for Healthy Immune Function

BEDTIME

Integrative Therapeutics  Cortisol Manager 2 caps one hour  before bedtime

  • Safe for use every night
  • Stress reducing sleep aid
  • Reduces cortisol levels for stress reduction and restful sleep.

https://us.fullscript.com/protocols/chilkov-dr-nalin-s-adrenal-stress-immune-support-kit

Treatment Plan should include 

Patient Teaching, Lifestyle and Dietary Guidelines and ongoing behavior change support

  • Dietary Guidelines -Nutrient Repletion-Glycemic Control
  • How to nurture parasympathetic tone
  • Sleep Hygeine
  • Self Regulation-Resilience- Stress and Mood Management guidelines
  • Monitoring Heart Rate Variability
  • Encourage Meditation-Tai Chi-Yoga-Deep Relaxation, Time in Nature
  • Acupuncture
  • Massage
  • Importance of Social Support
green tea extracts

Green Tea Extract Reduces Severity of Radiation-Induced Dermatitis

Breast cancer is the most common cancer affecting women worldwide. Radiation dermatitis affects nearly all women receiving radiotherapy for breast cancer.  http://repoceuticals.dk/pipeline/radiation-dermatitis/

new-breast-cancer

RID may result in less tolerance to treatment and even discontinuation of treatment. The patient may have skin changes ranging from faint erythema (reddening) and desquamation (peeling skin) to skin necrosis (death of skin cells) and ulceration, depending on the severity of the reaction.  Several studies demonstrate that topical green tea extract may be an effective prophylactic treatment.  

To make a strong hot water extract:  Place 8 tea bags of organic green tea into 1 cup of filtered or distilled water. Bring to a boil and simmer covered for 20 minutes. Place extract into sterile glass dropper bottle. (Available at most pharmacies).   Spray skin liberally before and after radiotherapy treatment.

The National Cancer Institute (USA) has developed 4 criteria for the classification of acute radiation dermatitis:

  • Grade 1 – Faint erythema or desquamation.
  • Grade 2 – Moderate to brisk erythema or patchy, moist desquamation confined to skin folds and creases. Moderate swelling.
  • Grade 3 – Confluent, moist desquamation greater than 1.5 cm diameter, which is not confined to the skin folds. Pitting oedema (severe swelling).
  • Grade 4 – Skin necrosis or ulceration of full-thickness dermis (middle layer of skin).

Hymes SR, Strom EA, Fife C. Radiation dermatitis: Clinical presentation, pathophysiology and treatment 2006. J Am Acad Dermatol 2006; 54:28-46. PubMed 

https://dermnetnz.org/topics/radiation-dermatitis

Epigallocatechin-3-gallate ameliorates radiation-induced acute skin damage in breast cancer patients undergoing adjuvant radiotherapy

In a study using topical Epigallocatechin-3-gallate forty nine patients topical EGCG was applied daily during radiotherapy treatment.  “Topical EGCG was applied daily, starting when grade I dermatitis appeared and ending two weeks after radiotherapy. The maximum dermatitis observed during the EGCG treatment was as follows: Grade 1 toxicity, 71.4% (35 patients); grade 2 toxicity, 28.6% (14 patients); there were no patients with grade 3 or 4 toxicity. The majority of the radiation-induced dermatitis was observed 1 week after the end of radiotherapy. EGCG reduced the pain in 85.7% of patients, burning-feeling in 89.8%, itching in 87.8%, pulling in 71.4%, and tenderness in 79.6%.”

Zhu W et al Oncotarget. 2016 Jul 26;7(30):48607-48613. doi: 10.18632/oncotarget.9495. PMID: 27224910; PMCID: PMC5217042.

Efficacy of Epigallocatechin-3-Gallate in Preventing Dermatitis in Patients With Breast Cancer Receiving Postoperative Radiotherapy: A Double-Blind, Placebo-Controlled, Phase 2 Randomized Clinical Trial 

A total of 180 eligible patients were enrolled, of whom 165 (EGCG, n = 111; placebo, n = 54) were evaluable for efficacy (median [range] age, 46 [26-67] years). The occurrence of grade 2 or worse RID was significantly lower (50.5%; 95% CI, 41.2%-59.8%) in the EGCG group than in the placebo group (72.2%; 95% CI, 60.3%-84.1%) (P = .008). The mean RIDI in the EGCG group was significantly lower than that in the placebo group. Furthermore, symptom indexes were significantly lower in patients receiving EGCG. Four patients (3.6%) had adverse events related to the EGCG treatment, including grade 1 pricking skin sensation (3 [2.7%]) and pruritus (1 [0.9%]).

Prophylactic use of EGCG solution significantly reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy for breast cancer.

Zhao H, Zhu W,  et al. JAMA Dermatol. 2022 Jul 1;158(7):779-786. doi: 10.1001/jamadermatol.2022.1736. PMID: 35648426; PMCID: PMC9161122.

tea-extracts

The effects of tea extracts on proinflammatory signaling

Tea extracts supported the restitution of skin integrity. 

Tea extracts inhibited proteasome function and suppressed cytokine release. 

NF-kappaB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. 

Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation

Pajonk F, et al, BMC Med. 2006 Dec 1;4:28. doi: 10.1186/1741-7015-4-28. PMID: 17140430; PMCID: PMC1698929.

doi: 10.1186/1741-7015-4-28. PMID: 17140430; PMCID: PMC1698929.

JAMA Derma

environmental-toxins

All Cancers Linked to Environmental Toxins

Making Environmental Health A Part of Health Care

Each month of the year is devoted to awareness of one or more cancers. September is devoted to multiple cancers.  

What do all of these cancers have in common?

There is an increasing volume of compelling evidence linking all types of cancer to environmental exposures.

Our knowledge of mechanisms linking exposures of toxicants to specific cancers is also increasing.  

environmental-pollution

There are two reasons that we as clinicians and care providers must be aware of the many contributing offenders and how to identify, assess, mitigate risk and safely remove body burden or toxicants in our patients.

Additionally, it is my practice to engage in patient education and patient teaching on the first or second visit to increase patient and family awareness about the importance of taking control of and reducing their toxic exposures as many toxicants are ubiquitous our homes, workplaces and communities.  Many toxicants include the use of common everyday products.    I also refer patients to these very reliable and up to date websites:  Environmental Working Group where foods, cleaning supplies, garden supplies are rated and their secondary site  Skin Deep Cosmetics Database for self-care and baby care products, including safe sunscreens.  They also have many downloadable publications for patients including 12 Hormone-Altering Chemicals and How to Avoid Them

Taking a good “ toxic exposures history” is important in all patients.  Of course, the very diagnostic methods and treatment modalities used in oncology are sources of toxic exposure as well!!  Many clinicians feel taking such a history from their patients will open us a Pandora’s box.

sewer-pollution

However, in the context of oncology, it is essential to do so, if only to bring awareness and to address the risk and health status not only of the patient, but also their family members.

My go to experts in this area include Dr. Walter Crinnion ND and Joseph Pizzorno, ND, both seasoned researchers and clinicians. They have recently published a well researched book  Clinical Environmental Medicine, which I consider required reading for all clinicians, especially those working with cancer patients.  There is a version for patients as well The Toxin Solution: How Hidden Poisons in the Air, Water, Food, and Products We Use Are Destroying Our Health--AND WHAT WE CAN DO TO FIX IT Dr. Crinnion’s has an excellent downloadable Toxic Exposure Questionnaire.  

The  American Academy of Environmental Medicine is an excellent resource for education and training and conferences where world-class experts convene.

Most in the patients control is their home environment and their food and water.

Fran Drescher’s Cancer Schmancer website has instructions for how to host a Detox Your Home Party.   

The first step is avoidance, avoidance, avoidance to reduce body burden, followed by appropriate supplements to help the body deal with what is there and finally safe and appropriate cleansing and detoxification interventions. Patients must also understand how to avoid re-exposure.

Resources:

Recommended Laboratories for Assessing Body Burden of Toxins 

(This is not a complete list and I have no financial relationship with any of these labs)

  • Great Plains Laboratory (heavy metals, environmental exposures, mycotoxins, glyphosate)
  • Genova Diagnostics (heavy metals, environmental chemicals)
  • RealTime Labs (Mold and Mycotoxins)
  • IMS Laboratory (Mold and Mycotoxins)
  • Quicksilver Scientific (Mercury)

*from a headline published in the New York Times