Tag: OutSmart Cancer

May 31, 2023

Boron and Prostate Cancer Control

Aside from non-melanoma skin cancer, prostate cancer is the most common cancer among men in the United States. It is also one of the leading causes of cancer death among men of all races and Hispanic origin populations.(1)

Dietary Boron intake is inversely correlated with prostate cancer incidence. (5)

Prostate risk is 52% lower in men whose diets contain at least 1.8mg boron daily. Prostate cancer risk reduction is correlated with boron intake. Recommended optimal daily dose of elemental boron is 3 mg/day for health maintenance.

Mechanisms of Action

Boron-containing compounds interfere with the physiology and reproduction of cancer cells through diverse mechanisms, including inhibition of serine proteases, NAD-dehydrogenases, mRNA splicing and cell division, receptor binding mimicry, and induction of apoptosis. (2)

In several studies Barranco et al (7, 8, 9, 10) demonstrate that increased boron intake is associated with lower levels of Prostate Specific Antigen (a biomarker for prostatitis and prostate cancer) as well as modulation of serum estradiol leading to increased expression of ER-beta receptors and decrease of ER-alpha receptors on tumor cells decreasing proliferation and growth signaling. Furthermore boron supplementation increased regulation of cell cycle arrest, increased apoptosis, decreased cell adhesion, migration and metastatic progression.

Boron decreases cancer associated inflammatory factors including hs CRP, TNFa, Interleukin-6 all of which are elevated in the tumor microenvironment. “Elevated hs-CRP is associated with an increased risk for breast cancer, obesity and metabolic syndrome (MetS) in children, atherosclerosis, unstable angina, insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), metastatic prostate cancer, lung cancer, adult depression, depression in childhood and psychosis in young adult life, coronary heart disease, and stroke." (2)

In murine study Insulin Like Growth Factor was significantly reduced in the prostate tumor cells in boron dosed animals. The IGF-1 signaling pathway promotes cancer progression and its down regulation is associated with lower risk of prostate cancer. (6)

“Increased intracellular concentration of borate activates borate transporters and leads to growth inhibition and increased apoptosis. “ (2) (3) (11)

Boron may act as a Histone De-acetylase Inhibitor (HDI). HDI’s act as therapeutic agents for cancer due to their impact on gene expression on growth arrest signaling, cell differentiation and apoptosis in cancer cells. (2)

Boronic Acid has been shown to inhibit hypoxia inducible factor (HIF) which is a physiological stimulus for tumor induced angiogenesis. Inhibition of HIF leads to inhibition of Vascular Endothelial Growth Factor (VEGF) and the production of capillary blood supply to tumor cells. Angiogenesis leads to exponential tumor growth and to metastatic progression of solid tumors. (11)

Plant foods rich in boron include Avocados, dried apricots, dried prunes, raisins, red kidney beans, lentils, almonds, hazelnuts, brazil nuts, pistachios, cashews and walnuts.

In summary, dietary and supplemental oral boron intake should be optimized to create a tumor microenvironment and cancer terrain that decreases risk of prostate carcinogenesis,proliferation and disease progression through angiogenesis and metastasis.

Selected References

1. American Cancer Society Statistics https://cancerstatisticscenter.cancer.org/

2. Scorei RI, Popa R Jr. Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anticancer Agents Med Chem. 2010 May;10(4):346-51. doi: 10.2174/187152010791162289. PMID: 19912103.

3. Romulus Ion Scorei and Radu Popa, Sugar-Borate Esters –Potential Chemical Agents in Prostate Cancer Chemoprevention DOI: 10.2174/18715206113139990124 Volume 13, Issue 6, 2013 Page: [901 - 909]

4. Kiliccioglu I, Konac E, Varol N, Gurocak S, Yucel Bilen C. Apoptotic effects of proteasome and histone deacetylase inhibitors in prostate cancer cell lines. Genet Mol Res. 2014 May 9;13(2):3721-31. doi: 10.4238/2014.May.9.17. PMID: 24854658.

5. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004;11(4):887-892.

6. Pizzorno, L. Review: Nothing boring about boron. Integrative Medicine Vol. 14, No. 4 August 2015

7. Barranco WT, Hudak PF, Eckhert CD. Evaluation of ecological and in vitro

effects of boron on prostate cancer risk (United States). Cancer Causes Control. 2007;18(1):71-77.

8. Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004;216(1):21-29.

9. Barranco WT, Eckhert CD. Cellular changes in boric acid-treated DU-145 prostate cancer cells. Br J Cancer. 2006;94(6):884-890.

10. Barranco WT, Kim DH, Stella SL Jr, Eckhert CD. Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells. Cell Biol Toxicol. 2009;25(4):309-320.

11. Shimizu K, Maruyama M, Yasui Y, Minegishi H, Ban HS, Nakamura H. Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1alpha inhibitors. Bioorg Med Chem Lett. 2010;20(4):1453-1456.

May 22, 2023

Modulating Extreme Adverse Effects of Immunotherapy Treatments

Today, more and more patients are avoiding toxic chemotherapy in favor of targeted cancer therapies. Among the many new therapies available are a class of immunotherapy drugs that take the brakes off of the immune system and mobilize T cells against tumor cells.

Because tumor cells have the capacity to disable T cells, this therapy addresses the huge problem of immune resistance in many cancers. Drugs in the class of PD1 and PDL1 inhibitors were some of the first to be developed. These drugs bind to PD1 or PDL1 receptors on the tumor surface and unleash the fury of the immune system upon the tumors by removing the inhibitory function of these ligands.

Nature has designed the immune system with both a gas pedal and a brake. The PD1 and PDL1 inhibitors are the brakes. Take off the brakes and the immune system is activated.

The best of outcomes with these treatments may result in complete tumor eradication, a truly miraculous outcome for some patients. I have a patient who came to me with Stage 4 Endometrial Cancer with Lung Metastases some years ago. After reduction of some of her tumor burden with surgery and rather brutal chemotherapy, her very forward-thinking Gynecologic Oncologist included a course of Keytruda (Pembrolizumab), which was a new immunotherapy treatment at the time.

The historical prognosis for this patient would have been certain eventual mortality for her metastasized aggressive cancer. However, she achieved a complete response and has been in remission and designated NED or No Evidence of Disease for many years now. This is a patient who most likely would not be alive today without the advent of PD1 -PDL-1 inhibitor therapy.

The problem with this class of drugs is that their use is very unskillful and very unpredictable. Some patients will respond with a modicum of mild to moderate systemic autoimmune inflammation while other patients will be disabled by furious, extreme, and damaging autoimmune syndromes. Some patients may die from extreme autoimmune activity. I had one patient who developed myocarditis and died within a few days of receiving his first dose. This was a prostate cancer patient whose sudden death was completely unexpected and not predicted.

These patients require a health model and safe, effective modulation of extreme auto-immune inflammation not provided by their oncology teams.

Some patients will have immune activation similar to a nice warm burning ember. They get the therapeutic benefit without extreme adverse effects. While other patients will respond with a forest fire of inflammation that must be suppressed aggressively with steroid medications for long periods of time. The adverse effects of long-term steroid therapy then become part of the clinical picture and challenge for these patients. In these circumstances, it IS reasonable to ask if the cure is worse than the disease itself?

My patient developed such severe colitis (a common adverse effect) that she visited the emergency room multiple times for fluid and electrolyte replacement due to extreme persistent watery diarrhea. Additionally, the nutritional status of this patient was also compromised and she became depleted in both calories and nutrients and developed sarcopenia.

Many cancer patients receiving PD1 and PDL 1 inhibitors are left with lifelong autoimmune disease. Most common are autoimmune arthritis, colitis, thyroiditis, dermatitis, pneumonitis, and associated loss of normal tissue and organ function. Some patients suffer ongoing chronic inflammatory pain syndromes.

Less prevalent, but also part of the long list of adverse effects are myocarditis, pericarditis, nephritis, hepatitis, pancreatitis, neuritis, vasculitis. Essentially, any tissue or organ can be impacted with associated loss of function and sequelae.

It is my practice to screen and monitor patients receiving cancer immunotherapies for the development of autoimmune syndromes and intervene early. If I have a patient with a history of inflammatory or autoimmune disorders I can predict that such patients are more likely to develop adverse effects.

Additionally, high levels of inflammation not only lead to pain syndromes but are also contributors to ongoing chronic fatigue as well as agitation, cognitive changes, sleep disruption, anxiety, and depression, and the stress of living not only as a cancer survivor but with a chronic and distressing autoimmune syndrome difficult to control and manage. It is my firm goal that Quality of Life must be a goal in all treatment plans for cancer patients and survivors.

If a patient has NO inflammatory adverse effects it is assumed that the patient is not going to benefit from the PD1/PDL1 inhibitor because there is no sign or symptom indicating immune activation. I always tell patients we should celebrate if they develop a rash or diarrhea because we know the drug is working!

In fact, it is my observation over many years of following patients who have received these therapies that when the course of immunotherapy treatment is completed those patients who continue to have low levels of inflammation continue to have the therapeutic benefit of tumor control. This is only an empirical observation on my part. For example, the endometrial cancer patient described above continues to have mild colitis and has remained in remission. Before the availability of these therapies, we would expect this patient to have a recurrence and to die of her advanced stage 4 metastatic disease within a few years of her diagnosis. Patients such as this with lung metastases historically had very poor prognoses and very high mortality rates. Patients with powerful and manageable responses to PD1 and PDL1 inhibitors may live a long time. While some patients do recur, some have not. We have not had decades of time to follow these patients as these treatments are relatively new. If nothing else, these treatments do extend the life of many patients.

How can we modulate the auto-immune adverse effects of these potentially curative immunotherapy treatments? I have taken the approach that we employ in Functional and Naturopathic Medicine in the management of auto-immune syndromes to turn down the volume on the immune inflammation just enough to reduce extreme side effects, damage, and loss of function without losing the therapeutic benefit of these immunotherapy treatments.

While we can rely on studies that have demonstrated that Omega 3 Fatty Acids, Vitamin D3, and Curcumin and a healthy microbiome can modulate auto-immune inflammation, there is a paucity of research on managing autoimmune syndromes related to immunotherapy adverse effects with the exception of steroids. (See selected references below.)

I share with you here my empirical clinical experience. I have employed this approach with several hundred patients since immunotherapies have come into wider use in oncology. Clinicians experienced in managing autoimmune syndromes will recognize the basic principles of care.

Anti-Inflammatory, Low Antigen Diet
Support for the healthy intestinal microbiome
Specific Nutriceutical-Phytochemical Interventions
- Omega 3 Fatty Acids (EPA DHA) recommended dose 4-6 grams daily SPMs Specialized ProResolving Mediators can also be considered 1-2grams daily
- Fat soluble Curcumin recommended dose 2-6 grams daily
- Vitamin D3 5,000-25,000iu daily (125mcg-625mcg).
  - Consider a loading dose of 50,000iu (1.25mg)

I always start at the lower end of the dose range and spread the dosing out into 3-4 doses over the day. The goal is to MODULATE but not SUPPRESS the therapeutic impact. It is also important to be mindful of the anticoagulant/platelet aggregation inhibitory effect of such an approach and to determine which patients may NOT be a candidate for high dosing due to thrombocytopenia or anticoagulant pharmaceutical therapies.

This approach has few negative drug-nutrient interactions. I have continued these inflammation-modulating therapies continuously for many years with most patients. Dosing is highly individualized to each patient towards the goal of supporting and promoting healthy function and quality of life.

For front-line clinicians interested in supporting the health of cancer patients and cancer survivors and learning and implementing my OutSmart Cancer® System developed over 35 years in practice, I encourage you to join our training program, Foundations of Integrative Oncology, self-paced online training with clinical supervision and mentoring. Go to aiiore.com.

There is a huge population of patients whose lives have been touched by cancer searching for a health model and skilled and knowledgeable clinicians.

Selected References:

Vitamin D and autoimmune diseases.
Illescas-Montes R, Melguizo-Rodríguez L, et al Life Sci. 2019 Sep 15;233:116744. doi: 10.1016/j.lfs.2019.116744. Epub 2019 Aug 8. PMID: 31401314

Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor-induced colitis.
Grover S, Dougan M, et al Cancer. 2020 Aug 15;126(16):3758-3767. doi: 10.1002/cncr.32966. Epub 2020 Jun 22. PMID: 32567084

Therapeutic Potential of omega-3 Polyunsaturated Fatty Acids in Human Autoimmune Diseases.
Li X, Bi X, Wang S, Zhang Z, Li F, Zhao AZ.
Front Immunol. 2019 Sep 27;10:2241. doi: 10.3389/fimmu.2019.02241. eCollection 2019. PMID: 31611873

Resolvins: Emerging Players in Autoimmune and Inflammatory Diseases.
Abdolmaleki F, Kovanen PT, et al
Clin Rev Allergy Immunol. 2020 Feb;58(1):82-91. doi: 10.1007/s12016-019-08754-9. PMID: 31267470

Curcumin in Autoimmune and Rheumatic Diseases.
Yang M, Akbar U, Mohan C.
Nutrients. 2019 May 2;11(5):1004. doi: 10.3390/nu11051004.
PMID: 31052496

Curcumin and autoimmune disease.
Bright JJ.
Adv Exp Med Biol. 2007;595:425-51. doi: 10.1007/978-0-387-46401-5_19. PMID: 17569223

Curcumin as an Adjuvant to Cancer Immunotherapy.
Paul S, Sa G.
Front Oncol. 2021 Aug 16;11:675923. doi: 10.3389/fonc.2021.675923. eCollection 2021.
PMID: 34485117

Gut Bacteria Influence Effectiveness of a Type of Immunotherapy. https://www.cancer.gov/news-events/cancer-currents-blog/2018/gut-bacteria-checkpoint-inhibitors. Feb 2018 NCI Staff

May 5, 2023

Acupuncture Provides Long Term Pain Relief for Breast Cancer Patients

Acupuncture Provides Long Term Pain Relief for Joint Pain Caused by Aromatase Inhibitors

In a randomized study conducted in November 2022 by a research team headed by Dr. Dawn Hershman MD, asked

“Does short-term acupuncture confer long-term reduction of joint pain related to aromatase inhibitors among women with breast cancer?”

This study demonstrated the benefits and highlights the durability of response to Acupuncture which significantly relieved joint pain caused by aromatase inhibitors in women diagnosed with early-stage, hormone receptor-positive breast cancer for one year.

Patients received 18 acupuncture treatments over 12 weeks.

This is a typical and traditional course of acupuncture applied to achieve a real pattern change and durable outcome. Controls included an second set of patients who received sham acupuncture and a third group of patients were told their were on a waiting list and received no treatment. All patients had been receiving AI therapy for at least 30 days at inception.

Patients were monitored for another 40 weeks and thus were followed for a full year.

“The study was conducted at 11 academic and community sites within the National Cancer Institute Community Oncology Research Program. Sites were required to have 2 trained acupuncturists for the duration of the trial.” (1)

Aromatase Inhibitors (AI) are widely used in the treatment of estrogen receptor positive breast cancers. AI inhibit the transformation of androgens in the tissue into biologically active estrogens which can bind to the receptors on breast cancer cells sending a growth signal. Aromatase inhibitors are usually prescribed after surgery for five to ten years to reduce risk of recurrence in post-menopausal women.

Commonly used first line AI include Arimidex (anastrozole), Aromasin (exemestane) and Femara (letrozole).

However a common adverse effect is joint pain and stiffness which contributes to non-compliance with therapy for more than 50% of breast cancer patients. Many patients do not disclose to their physicians that they have discontinued AI therapy due to poor quality of life and persistent pain.

Researchers concluded that “Acupuncture was associated with a statistically significant decrease in aromatase inhibitor–related joint pain that persisted at 40 weeks after discontinuation of the intervention, suggesting long-term benefits of this therapy.”

(1) The study showed that a full course of therapeutic acupuncture over three months led to a durable change in perceived pain at 52 weeks compared to controls. This study did not follow women past 52 weeks.

Subsequent systemic reviews and meta-analyses (2, 3) of acupuncture trials have also demonstrated efficacy and long term beneficial effect.

1.Hershman, D. Et al Comparison of Acupuncture vs Sham Acupuncture or Waiting List Control in the Treatment of Aromatase Inhibitor-Related Joint Pain: A Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2241720. doi: 10.1001/jamanetworkopen.2022.41720. PMID: 36367721; PMCID: PMC9652759.

2. Liu X, Lu J, Wang G, et al. . Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: a systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. doi:10.1177/1534735420980811 - DOI - PMC - PubMed

3. MacPherson H, et al. ; Acupuncture Trialists’ Collaboration . The persistence of the effects of acupuncture after a course of treatment: a meta-analysis of patients with chronic pain. Pain. 2017;158(5):784-793. doi:10.1097/j.pain.0000000000000747 - DOI - PMC - PubMed

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May 3, 2023

VITAL TALK: Learn to Communicate Effectively with Patients Experiencing Serious Illness

“Just as no doctor is born knowing how to handle a scalpel, the same is true for how to communicate effectively with seriously ill patients and their families. We believe every clinician can become a better communicator.”

I met oncologist Dr. Tony Back, MD at a meditation retreat focused on working skillfully and mindfully with patients with serious, life changing illnesses as well as end of life care. Dr. Back is affiliated with the Center to Advance Palliative Care at Fred Hutchinson Cancer Center in Seattle, Washington and has combined his years of clinical oncology experience with his recognition that patients and clinicians require more skillful and effective conversations in the midst of emotionally charged and medically complex discussions. Dr. Back has developed online and in person trainings called Vital Talk for clinicians to LEARN TO COMMUNICATE EFFECTIVELY WITH PATIENTS EXPERIENCING SERIOUS ILLNESS. His mission is “To Elevate Patient Care with better communication”.

Dr. Back and the Vital Talk mission is “that every seriously ill patient will be surrounded by clinicians who can speak about what matters most and match care to values.”

Vital Talk Trainings help clinicians to Master Tough Conversations

Whether in person or online, clinicians feel safe practicing newly learned skills through VitalTalk’s evidence-based training methodologies.

Some tips from a Vital Talk trained physician

Give yourself grace
Lean in with emotion, heart and feeling
Respond with empathy.
Explore and ask the patient to tell you more.
Ask permission to talk about a topic (scan results, disease progression, end of life care)

[READ MORE]

EVIDENCE-BASED SKILLS Vital Talk TRAINING COURSES

Elevate patient care with better communication
Explore best-practice communication methodologies and tools, as well as our rich community of support to better serve the needs of patients with serious illness and their families.
Support clinicians in learning to communicate effectively and compassionately with patients living with serious illness.

We are living in the midst of an aging patient population in the United States. Therefore our patients are increasingly at risk of developing more serious illnesses, experiencing co-morbidities and facing many life changes of loss and limitation, frailty and mortality. Cancer patients of all ages face immense challenges and must redefine their sense of self and examine their values and relationship to life, suffering, death and dying. These challenges may be turned into gateways to transformation. I counsel my patients to reframe their cancer journey so that the challenges that they face become opportunities for growth, insight and wisdom and not just suffering, grief and loss. These conversations require clinicians to develop greater communications skills and the ability to be comfortable engaging in these dialogues.

It is my experience that clinicians who are inspired to work with cancer patients are motivated by the drive towards making a difference, the intellectual challenge of the complexity of cancer and the deep meaning that arises in meeting patients at the edge where the rawness and overwhelm of being a cancer patient can be transformed into a profound healing journey of awareness and transformation.

I highly recommend that all clinicians continue to develop their clinical skills so that they can be fully present, capable and comfortable for participating in these most tender, human and meaningful conversations.

I always feel it is a privilege and an honor to be allowed to accompany a patient and their family on their journey and to be able to guide them into deeper meaning and a greater sense of connection to each other and to all of life.

I encourage you to explore The Vital Talk website where you will find information on their programs and trainings but also Free Downloadable Tools and Guides to get you started

https://www.chooseyourpath.vitaltalk.org/

https://www.vitaltalk.org/resources/

Please do share your stories with us!!

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April 24, 2023

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.

The 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.

Curcumin 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.

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

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April 19, 2023

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.

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.

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.

In 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.

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April 12, 2023

Does Stress Cause Cancer?

Lifestyle Factors That Impact Breast Cancer Risk

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.

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

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

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April 1, 2023

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/

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.

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.

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March 22, 2023

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.

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.

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

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March 13, 2023

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.

Rhodiola 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)

Rhodiola 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

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