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The Role of Diet & Supplementation in Cancer Care

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The role of diet & supplementation in cancer care
Pets with cancer are very common in small animal practices. Learn more about how diet can be a tailored treatment plan.

The role of diet & supplementation in cancer care
By
Sue Armstrong, MA, VetMB, VetMFHom, CertIAVH, MRCVS, RsHom
-
January 31, 2013



Pets with cancer are very common in small animal practices. Learn more about how diet can be a tailored treatment plan for some patients.
Cancer is one of the most common issues we deal with in small animal practice. Just as the causes are complex, so are the treatment options. More than any other disease, cancer has people going on the internet and adding every supplement they can find that’s claimed to cure cancer. This is one area in which the integrative practitioner, even if untrained as a veterinary herbalist or nutritional expert, has a responsibility to help guide people so decisions such as diet choices can be tailored to each individual.

Why diet is key
The importance of diet in treating and preventing cancer is long established. Some practitioners claim to treat cancer by dietary manipulation alone, focusing in particular on the elimination of cancer toxins and providing potentially deficient essential nutrients to support the immune system and liver.1 Many of the diets advocated for the treatment of cancer in humans are vegetarian, but this may not be applicable to obligate carnivores such as the cat and carnivore-biased omnivores like the dog.

Growing evidence supports the basic principle in cancer nutrition of minimizing simple sugars and complex carbohydrates, and favoring protein and unsaturated fats as the main energy sources for humans, cats and dogs. This is based on studies of the metabolic requirements of cancer versus host cells. Cancer cells use protein for energy and will utilize certain amino acids, such as arginine, at the expense of the host.

Fats provide more calories per gram than protein and carbohydrates, an advantage to very sick animals able to ingest only small amounts of food. Most animals find fats more palatable. The biochemical response to food deprivation (even 24 hours of anorexia) leads to substantial dependence on fat derived fuels.

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As cancer progresses, alterations in normal patient metabolism occur; often these changes are irreversible without treatment and adequate nutritional support. Diet in cancer patients can be extremely challenging when the animal is inappetant, able to swallow only small amounts of food, or is vomiting. Cachexic patients need high energy in the form of fat, and even carbohydrates may have to be reintroduced at this stage, even though they give the tumor an energy supply.

Ideally, I prefer animals to be taken off refined commercial diets and put on raw whole food diets. Guardians need good instructions on how to create a good diet for their animals. They must be willing to spend the time putting the diet together every day, using high quality human grade foods. Some excellent companies produce well-formulated raw food diets that are complete and take the hard work out of it for clients with limited time. Cheap fatty meats laden with carcinogens and old vegetables from the bottom of the fridge are as unhealthy to the animal as a refined diet. Dogs that have been used to commercial diets all their lives and are now very ill with cancer have to be transitioned carefully (it may not even be possible or advisable to change some cases); I do not use diets high in bone for these animals. Those with cachexia may not be able to handle raw food diets. At this stage, cooking the food, feeding it warm and not cold, and using high energy convalescence products is required.

The home-formulated raw diet I use is essentially based on 2:1 meat/meaty bone to vegetable/fruit with an emphasis on human grade organic food. I also pay attention to the full spectrum of colors in fruit and vegetables to give the animal a good mineral/vitamin spread. if vitamin/mineral supplements are used, they must be bio-available and ideally sourced from whole plants. Additions to the basic diet include eggs, cottage cheese (especially if the liver is showing measurable signs of stress), spirulina, wheat grass, alfalfa juice and barley greens.

Reducing the acid load is helped by vegetables, fruits and the additions mentioned above combined with the elimination of refined carbohydrates, grains, sugars and dairy foods. Evidence indicates the cancer progresses more in an acid environment. There are also theories that take this understanding down to a basic imbalance between active ionized potassium providing positive electric potentials in health, versus negative potentials created by the ionization of sodium in disease. it is suggested that alongside detoxification, activated ionized minerals are essential for healing. The addition of digestive enzymes may be useful, especially in animals that have been fed refined diets for years.

Supplements for cancer
Many supplements, in addition to Omega-3 fatty acids and l-arginine (see below), are commonly used alongside basic cancer nutritional therapy. Most are taken directly from human cancer care, so there is little evidence available about dose rates, toxicity reports and contraindications in cats and dogs. in addition, there is a huge tendency for clients to want to use everything possible with little understanding of the pharmacology of the substances used. This is of particular concern in animals undergoing chemotherapy and radiotherapy, as some supplements can radically alter the availability and toxicity of these potent treatments. Since some common supplements are immune modulators that may enhance the proliferation of tumor cell lines, they are not good for lympho-proliferative tumors.

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Here are some common supplements that have a growing evidence base for efficacy and safety in animals, and that i consider for my cancer patients:

Antioxidants, including vitamins A, C, E, beta-carotene and lutein are now added in increased quantities to many commercial pet foods, with anti-cancer claims being made for some of these foods. Chronic oxidative stress with formation of reactive oxygen species, especially when antioxidant capacity is inadequate, has been hypothesized to contribute to DnA damage, malignant transformation, and eventual tumor development in numerous species.

Very little is known about the potential anti-neoplastic effect of antioxidant supplementation in dogs and cats. However, the beneficial effects of dietary antioxidant supplementation on the development of malignant lymphoma and other neoplastic lesions in mice have been demonstrated at the Department of radiation oncology, University of Pennsylvania School of Medicine.

The main message I would give about antioxidants is that they are of most use in prevention. They are often contraindicated in active cancer treatment, particularly cases undergoing treatments that rely on pro-oxidant cell death.

Mushrooms are increasingly shown to contain different classes of biologically active compounds with strong immunemodulating and anticancer properties. one extensively used in both traditional herbalism and modern clinical practice is Coriolus versicolor, also known as yun-Zhi. The chemical composition of the mushroom is very complex. Among various bioactive components derived from hot water and standardized ethanolwater extracts of C. versicolor, polysaccharopeptides (PSP) and protein-bound polysaccharides (PSK) have the strongest biological activity. The main effects on cancer are as follows:

  • PSP and PSK can inhibit the proliferation of leukemia, lymphoma, hepatoma, breast, lung and prostate tumor cell lines. Their antimetastatic activity has also been demonstrated.
  • PSP contributes to tumor eradication by stimulating both humoral and cell-mediated immune responses.
  • PSP and PSK increase the synthesis of interferon (IFN)-c and interleukin (IL)-2.
  • They enhance T-cell proliferation.
  • They stimulate macrophage-derived nitric oxide production and counteraction of the immuno-suppression induced by cytotoxic drugs.
Other mushrooms are also of considerable interest and frequently used in mixed mushroom preparations with or without the use of Transfer Factor – Cordyceps sinensis, Ganoderma lucidum, Grifola frondosa are just a few. Each has a specific array of immunemodulatory effects and needs to be carefully selected and understood, especially when lympho-proliferative diseases are present or when chemotherapy is used.

Curcumin is an extract from turmeric (Curcuma longa). it can be an extremely useful supplement in many canine cancers. it has been shown to have the following effects in relation to cancer:

  • Anti-proliferative effects in cancer cell lines
  • Induces apoptosis
  • Anti-angiogenic factors
  • Impedes tumor growth and metastases
  • Helps control matrix metalloproteinase activity
  • Anti-infl ammatory
  • Pro-oxidant in high dose
It is generally well tolerated, although it has documented mild blood thinning properties so should not be given in cases of haemorrhagic tumors or immediately post surgery. it can be poorly absorbed so the quality of the product with regard to the percentage of curcuminoids present is essential. Curcumin can selectively enhance the cytotoxicity of chemotherapy agents, and in addition may reduce negative side effects. Due to these altered responses, any veterinary surgeon in control of chemotherapy must be aware if this supplement is being used.

Artemisinin is the active extract from the herb sweet wormwood (Artemisia annua). It has been shown to have the following properties in relation to cancer:

  • Anti-angiogenic
  • Increased apoptosis
  • Selective cytotoxicity against cancer cells due to their higher iron content when compared to normal cells.
Artemisinin should not be used with high antioxidant supplements that act to buffer and protect against free radicals, because its cytotoxicity depends on the production of free radicals produced as a result of its interaction with iron in the cancer cell. It should not be given during or after radiotherapy for up to two months. radiotherapy causes the release of iron into local tissue, which could potentially lead to increased local cell damage.

In conclusion
You need to assess each cancer case individually to determine the animal’s nutritional requirements, as well as the frequency, consistency and method of delivering the food. With supplements, it is safer to give none than everything under the sun. if you do not know how they work, start with a corrected and appropriate diet and do nothing else. And caution your clients, as nothing provokes panicked self-treatment more than cancer.

References
1 Gerson M. Gerson Therapy Handbook, 5th Edition, Totality Books (1st Edition 2007).

2Ogilvie G, Vail DM. “Metabolic alterations and nutritional therapy for the veterinary cancer patient.” Withrow SJ, MacEwan EG. Clinical Veterinary Oncology, Philadelphia, WB Saunders, 1996.

Resources
Klemente R, Kammerer U. “Is There a Role for Carbohydrate Restriction in the Treatment and Prevention of Cancer?” Nutr Metab, 2011, 8 (75), Biomed Central Ltd

Mauldin G. “Nutrition and the Small Animal Cancer Patient”, WSAVA,World Congress, Vancouver, 2001

Monro J. “Treatment of Cancer with Mushroom Products”, Archives of Environmental Health, Aug 2003, Vol. 58, No. 8.

Clemmons RM. “Integrative Treatment of Cancer in Dogs”, University of Florida, Department of Small Animal Clinical Sciences.

Schoen & Wynn. Complementary and Alternative Veterinary Medicine, Mosby, Inc.,1998.

White C. “Cancer Smart Bomb, Part 1: An Idea from Ancient Chinese Medicine”, New Horizons, Brewer Science Library, Summer 2002.
 

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KetoPet Sanctuary: ketosis, cancer and canines, part 1 & part 2

By
Chelsea KentShannon L. Kesl, PhDStacy A. Hodges, DVMLoren Nations, DVM, DABVP June 25, 2019

KetoPet Sanctuary: ketosis, cancer and canines, part 1 - IVC Journal

KetoPet Sanctuary: ketosis, cancer and canines — Part 2
Non-profit organization KetoPet Sanctuary has tested the feasibility of using a ketogenic diet as an adjunctive therapy in dogs with cancer. In the second part of this article, we’ll look at the overall results of the program, along with some case studies
 

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Bridging the gap in veterinary oncology
By
Erin Bannink, DVM Diplomate ACVIM (Oncology), GDipl VCHM, CVA (IVAS)
-
July 10, 2019



Integrative Oncology leverages the advances of Western biomedicine by downsizing the cancer burden while simultaneously utilizing the tools we have available to us from other traditions of medicine. The goal is to make the body a less hospitable environment for cancer and support its natural healing processes.
Research is accumulating on how diet, exercise, lifestyle, stress, herbal medicine and acupuncture impact the development of and recovery from cancer in humans. Recent studies also show that the health of the gut microbiome may impact individual responses to conventional cancer therapies like chemotherapy and immunotherapy. By combining the strengths of the Western biomedicine paradigm with those of traditional medicine paradigms, which have a long history of supportive lifestyle and natural medicine therapies, we open the door to improving outcomes for our animal cancer patients.

My clinical experience shows that when lifestyle and nutritional interventions, including diet, exercise, emotional wellness, select supplements, acupuncture and herbal medicines, are appropriately implemented alongside thoughtfully-applied patient-specific biomedicine therapies, patient well-being improves — and often, so do patient outcomes. When patient well-being improves, client satisfaction improves, and the experience of the whole veterinary team becomes more rewarding.

When clients are presented with broader options and supported in taking an active role in their pets’ healing, the experience of cancer treatment can become one of empowerment and hope rather than despair and hopelessness.

Toward a paradigm of integrative cancer care
At its root, cancer is a chronic disease characterized by the dysregulation of multiple body processes, including chronic unmitigated inflammation, the failure of appropriate immune responses, and aberrant molecular signaling resulting in an alteration of the body’s “ecosystem”. These shifts in the body’s internal environment lead to epigenetic changes, which ultimately result in altered gene expression, abnormal tissue growth, and the creation of a tumor microenvironment that supports the survival, growth and metastasis of dysregulated cells. In many veterinary patients, cancer does not manifest appreciable signs until it is in advanced stages or has become a life-threatening medical emergency.

Given that cancer is a multifactorial manifestation of disease, an effective approach to healing also needs to be multifactorial. Systemic Inflammation, angiogenesis and immune dysfunction are all recognized factors contributing to cancer development, growth, persistence and metastasis. When I discuss the role of herbs in cancer management with clients, I explain that many herbs have been shown to mitigate inflammation in the body, inhibit angiogenesis, and bolster anti-cancer immune responses. These actions are in addition to their uses in alleviating the side effects of conventional cancer therapies or the clinical signs resulting from the cancer itself.

Evidence-informed Chinese herbal medicine in cancer care
As my specialized training lies in oncology and Chinese Herbal Medicine, I will focus on the role the latter can play in an evidence-informed integrative approach to cancer patient care.

Within the Traditional Chinese Herbal Medicine (TCHM) paradigm are plant-based treatments containing compounds that are currently being researched and exploited for their anti-cancer actions. Many of these actions parallel the mechanisms of metronomic chemotherapy, immunotherapy and targeted cancer treatments, while offering more balanced, or broader-acting and adaptogenic actions in the body as a whole.  A number of herbs exhibit the potential to prevent or reverse multiple drug resistance (MDR), the main cause for chemotherapy resistance, and are under heavy investigation for development as pharmacological agents. For these reasons, they present an attractive option for maintenance therapy after the completion of conventional treatments, and also hold the potential for effective additions to our combination therapy protocols.

Integrative therapy utilizing TCHM has been associated with prolonged survival in a number of human cancer types, such as metastatic mammary carcinoma, lung cancer, pancreatic cancer and gastric cancer. Conversely, evidence also indicates that careful patient-specific considerations are warranted. For instance, some herbal therapies might promote the growth of certain types of cancer, such as hormone responsive breast cancer; and other specific herb-chemotherapy combinations could potentially interfere with the efficacy of certain chemotherapy drugs. It is, therefore, important to respect the importance of patient-specific prescribing.

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An extensive review of herb pharmacokinetics and drug-herb interactions is beyond the scope of this article. However, we need to acknowledge that the importance of appropriate patient-oriented TCHM diagnosis and prescribing cannot be overemphasized. And in an evidence-informed approach to Integrative Oncology, efforts to stay up to date with the current literature on this topic, especially when combining herbal medicines with conventional treatments, are vital to safe, effective and informed integrative treatment.

A substantial amount of research can be found on individual herbs and herb-derived compounds in cancer care. Following are a few select examples of TCHM formulas that may be helpful in cancer patient care and in vivo research supporting their use.

Supporting immune function
1. Dang Gui Bu Xue Tang: Oral administration modulated immune activity in tumor-bearing mice through:

  • increased cytotoxic T lymphocytes and NK cell numbers
  • down-regulated activated T helper cell (CD4+/CD25+).
2. Xiao Chai Hu Tang: Improved immune function in tumor-bearing mice.

Supporting body condition
Xiao Chai Hu Tang: Oral administration in tumor-bearing mice at a dose of 50 and 100 mg/kg resulted in:

  • slowed tumor growth
  • prevented loss of body condition
  • lowered tumor-related elevations in serum IL‑6
  • attenuated muscle atrophy by affecting myoblast proliferation and differentiation
  • suppressed pro-cachectic inflammatory cytokine production via inhibition of nuclear factor‑κB.
Supporting appetite
Liu Jun Zi Tang: Oral administration improved appetite through:

  • enhanced ghrelin signaling, which is involved in appetite regulation
  • improved gastric motility via hesperidin content.
Pharmacokinetic evaluation of the formula suggests that its effects on ghrelin are:

  • exerted via synergistic action of multiple ingredients rather than attributable to one ingredient alone
  • due to local direct action in the stomach.
Supporting energy
Tao Hong Si Wu Tang: Oral administration prevented fatigue in mice.

Supporting immunotherapy
Shi Quan Da Bu Tang: Oral administration improved in vivo tumor vaccine antigen-specific immune response over vaccination alone resulting in

  • slowed tumor growth
  • improved survival time
  • enhanced antigen presenting ability of dendritic cells (in vitro)
  • improved phagocytosis (in vitro).
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Decreasing treatment-related toxicity
  • Liu Jun Zi Tang: Used along with standard antiemetic therapy, and evaluated in a randomized phase II study in humans, this herbal formula showed additive relief of chemotherapy-related vomiting, nausea and anorexia compared to standard antiemetic therapy alone.
  • Xiao Chai Hu Tang: Treated and prevented induced gastritis and gastric ulceration in rats.
  • Long Dan Xie Gan Tang: Sorafenib (in the same class of drugs as the veterinary tyrosine kinase inhibitor Toceranib) was evaluated with co-administration of Long Dan Xie Gan Tang. When given together, there was no significant alteration in chemotherapy blood levels or metabolism, but the liver toxicity induced by Sorafenib was mitigated.
Preventing cancer development and growth
  • Shi Quan Da Bu Tang: Oral administration prevented development of hepatic carcinoma in rats.
  • Xiao Chai Hu Tang: Oral administration inhibited hepatocellular carcinoma growth in vivo.
  • Xue Fu Zhu Yu Tang: Oral administration significantly improved survival time and demonstrated anti-tumor activity in experimentally-induced liver sarcoma in mice.
Optimizing life
After over 12 years of clinical veterinary oncology practice, the wellness benefits I’ve seen with my patients receiving an integrative approach are so consistent that it has become ethically difficult for me to practice without offering these options. It has significantly improved my job satisfaction, and my clients are grateful to have their requests for assistance in selecting effective supplements, natural medicine options, nutritional interventions and stress management supportively addressed.

Even in cases where “cure” isn’t achieved, quality of life can improve. I have seen patients live comfortably with their cancer for extended periods of time, far beyond the prognosis we typically see with conventional treatments. I have seen prolonged disease stabilization with herbal treatments. And although it doesn’t happen for every patient, I have seen tumors shrink with aggressive herbal medicine and lifestyle interventions alone when our initial intent was palliative care.

I now practice Integrative Oncology almost exclusively. I also offer Integrative Oncology Telemedicine Consultations to provide integrative assistance to veterinarians and support those managing patients with cancer. This arises from a desire to help bridge the gap between conventional and alternative medicine world-views, in the hope of bringing pet owners and the veterinary profession together on a comprehensive and effective path to wellness. When we learn to more effectively bridge this gap, these treatments will become more accessible to our profession as a whole.

As we develop a broader view of health and healing, we are empowered to take an active role in treatment and recovery. Treatment then becomes not  about a “battle against cancer” but about how we optimize life.

This focus is emotionally  healthier both for us as clinicians and for our clients as pet guardians. It allows us to focus on wellness rather than disease, while effectively supporting the human-animal bond. And in the end, whether the cancer itself is the cause of death, or whether it is eliminated, the quality of the life that is lived during the treatment journey is almost always improved.

References
Chen, X. “Anti-Helicobacter pylori and Anti-Inflammatory Effects and Constituent Analysis of Modified Xiaochaihutang for the Treatment of Chronic Gastritis and Gastric Ulcer”, Evidence-Based Complementary and Alternative Medicine, 2018.

Cheng YY. “Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics”, Journal of Food and Drug Analysis, 2018.

Fujitsuka, N. “Rikkunshito, a ghrelin potentiator, ameliorates anorexia–cachexia syndrome”, Front Pharmacol, 2014.

Hsieh, CC. “Dang-Gui-Bu-Xai-Tang modulated the immunity of tumor bearing mice.” Immunopharmacol Immunotoxicol, 2003.

Hung, KF. “Complementary Chinese herbal medicine therapy improves survival of patients with gastric cancer in Taiwan: A nationwide retrospective matched-cohort study”, J Ethnopharmacol, 2017.

Kim, A, et al. “Sosiho‑tang ameliorates cachexia‑related symptoms in mice bearing colon 26 adenocarcinoma by reducing systemic inflammation and muscle loss”, Oncol Rep, 2016.

Kitagawa, H. “Pharmacokinetic Profiles of Active Ingredients and Its Metabolites Derived from Rikkunshito, a Ghrelin Enhancer, in Healthy Japanese Volunteers: A Cross-Over, Randomized Study”, PLoS one, 2015.

Kuo, YT. “Complementary Chinese Herbal Medicine Therapy Improves Survival of Patients With Pancreatic Cancer in Taiwan: A Nationwide Population-Based Cohort Study”, Integr Cancer Ther, 2018.

Liu, W. “Mechanisms of Antiulcer Effect of an Active Ingredient Group of Modified Xiao Chaihu Decoction”, Evidence-Based Complementary and Alternative Medicine, 2018.

Mao, Y et al. “Network pharmacology-based and clinically relevant prediction of the active ingredients and potential targets of Chinese herbs in metastatic breast cancer patients”, Oncotarget, 2017.

Ohnishi, S. “Additive effect of rikkunshito, an herbal medicine, on chemotherapy-induced nausea, vomiting, and anorexia in uterine cervical or corpus cancer patients treated with cisplatin and paclitaxel: results of a randomized phase II study (JORTC KMP-02)”, J Gynecol Oncol, 2017.

Suzuki, H. “Cancer cachexia pathophysiology and translational aspect of herbal medicine”, Jpn J Clin Oncol, 2013.

Tatsuta, M. “Inhibition by shi-quan-da-bu-tang (TJ-48) of experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats”, Eur J Cancer, 1994.

Takeno, N. “Immune adjuvant effect of Juzentaihoto, a Japanese traditional herbal medicine, on tumor vaccine therapy in a mouse model”, International Journal of Oncology, 2015

Wang, BR..”Coprescription of Chinese herbal medicine and Western medication among female patients with breast cancer in Taiwan: analysis of national insurance claims”, Patient Prefer Adherence, 2014.

Wang, P. “Overcome Cancer Cell Drug Resistance Using Natural Products”, Evidence-Based Complementary and Alternative Medicine, 2015.

Wang, Q. “Maintenance Chemotherapy with Chinese Herb Medicine Formulas vs. with Placebo in Patients with Advanced Non-small Cell Lung Cancer After First-Line Chemotherapy: A Multicenter, Randomized, Double-Blind Trial”, Front Pharmacol, 2018.

You, JS. “Effects of Xuefu Zhuyu Tang and Mitomycin C on Liver Tumors in Mice”, Chang Gung Med J, 2003.

Zheng, N. “Current Understanding on Antihepatocarcinoma Effects of Xiao Chai Hu Tang and Its Constituents”, Evidence-Based Complementary and Alternative Medicine, 2013.

This article has been peer reviewed.
 

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Integrated approaches to canine cancer: Mitigation of treatment side effects
By
Demian Dressler, DVM
-
May 29, 2019

Integrated approaches to canine cancer: Mitigation of treatment side effects - IVC Journal



Six integrative approaches to alleviating the side effects of chemotherapy and radiation in dogs with cancer.
This multi-part article will provide one integrative clinical viewpoint on ways to improve longevity and quality of life for veterinary cancer patients. Functional subjects to be covered include chemotherapy and radiation side effect mitigation; cancer cell suicide induction; immune support; and extracellular matrix therapies. By focusing on each of these functional groups during an extended cancer consultation appointment, the veterinarian can work with the client to develop a high quality cancer care plan for animal patients. In Part 1, we’ll focus on the mitigation of treatment side effects.

Chemotherapy and radiation side effect mitigation
Reducing cancer cell burden in the canine patient is a central concern for the veterinarian. It can be accomplished in a variety of ways. The foundation of the conventional cancer approach includes surgery, chemotherapy and radiation. The latter two modalities have traditionally used some version of the Maximum Tolerated Dose (MTD) paradigm.

The MTD approach uses the highest possible treatment dose in an effort to eradicate the highest number of cancer cells. Dose ranges are limited by toxicity.

A frequent problem is that the gains in predicted patient life expectancy may not be adequate enough to justify this treatment. Side effects, quality of life, logistics and cost are considerations for both owner and clinician.

Taking proactive steps to help address this difficulty is, therefore, a logical clinical step.

Specific approaches for reducing side effects in canine cancer care
1. Metronomic chemotherapy with alternate COX-2 inhibitors
“This approach may be at least as effective as conventional chemotherapy with a lower risk of toxicity.” – Veterinary Clinics of North America Small Animal Practice, 2014

One approach to reducing the problems encountered in MTD chemotherapy is the use of metronomic chemotherapy. The goal of this strategy is the management of canine cancer by using lower drug doses than MTD chemotherapy, as well as continuous dosing regimens.

Metronomic chemotherapy is oriented toward life quality and the management of cancer as a chronic disease by reducing metastasis and local spread. It may also be advantageous from financial and logistic standpoints, because the agents used in these protocols are oral and administered at home.

Cancers such as mast cell tumor, lymphosarcoma, hemangiosarcoma, soft tissue sarcoma, transitional cell carcinoma, osteosarcoma, oral melanoma, fibrosarcoma and mammary adenocarcinoma may all be treated using a metronomic approach.

The medications classically used include COX-2 inhibitors, cyclophosphamide and possibly doxycycline. However, low-dose toceranib (Palladia®), lomustine and chlorambucil can also be used in a metronomic fashion.

Traditionally, piroxicam was the COX-2 inhibitor included in metronomic protocol research. However, this drug is rapidly absorbed and has a half-life of approximately 40 hours in the dog. With dosing regimens of every 24 hours, piroxicam tends to accumulate systemically, leading to fairly frequent toxicities.

Selecting COX-2 inhibitors with a higher safety margin are preferred by the author for cancer management. High-potency botanical polyphenol COX-2 inhibitors often fit in the context of a life quality-centered (metronomic) cancer plan. These include bioavailability-enhanced formulations of curcumin, boswellia or citrus bioflavonoids. These compounds have additional benefits, including anti-metastatic effects and the sensitization of neoplastic cells to the effects of chemotherapy and radiation treatment.

Apocaps® CX is a commonly-used source of botanical COX-2 inhibitors with chemosensitizing and radiosensitizing effects. It is designed for dogs and has a high safety margin. Note that if Apocaps® is administered with corticosteroids or pharmaceutical NSAIDS, it is advisable to use approximately half the labeled dose. This nutraceutical is best given with at least a small amount of food.

Apocaps-dosing.png


Although close patient follow-up and monitoring is still important, metronomic chemotherapy using alternate COX-2 inhibitors is one way to achieve lower pharmaceutical dosing and improved life quality.

2. Cordyceps
Pre-emptive measures to reduce toxicity in canine cancer case management has is receiving increased attention. Veterinarians can take anticipatory steps by using supportive strategies specific to toxicity type to preclude or mitigate known toxic events.

Also known as “caterpillar fungus”, cordyceps has applications in side effect mitigation of various at-risk organs, and has been used in dogs for over 15 years. Clinical applications for the use of cordyceps in canine cancer management include kidney toxicity encountered with the use of methotrexate, cisplatin or carboplatin.

Evidence indicates that cordyceps may also reduce the risk of pulmonary toxicity sometimes seen with the use of lomustine and rabacfosadine (Tanovea®). It additionally assists in reducing bone marrow suppression, a common side effect of wide array of chemotherapy drugs and in some applications of radiation therapy.

Cordyceps has not been shown to interfere with the beneficial effects of chemotherapy or radiation; on the contrary, it may enhance them. It may create a mild cortisol increase, which supports it in its role of reducing physiologic stress. However, in cases of untreated hyperadrenocorticism, the author prefers to avoid it.

In general, cordyceps has a high safety margin.

Cordyceps dosing
When using a conveniently-sourced cordyceps formulation labeled for humans, the author typically increases the label dose on a per pound basis by a factor of three for clinical use in the canine.

3. Glutamine
Glutamine is an amino acid that is useful in helping to reduce the diarrhea common with both chemotherapy and radiation. There is mixed evidence that glutamine may also help mitigate the oral mucosal ulcers occasionally resulting from radiation.

Cancer cachexia is common in advanced canine cancer, representing a loss of muscle mass. Myocytes have a preference for glutamine as a metabolic fuel source, so glutamine supplementation may have an additional benefit in this regard.

Glutamine does not show evidence for interfering with chemotherapy or radiation, and in fact, may have a therapy-enhancing effect.

In the author’s opinion, however, glutamine should not be used in cases of brain cancer, as it may promote net enhancement of CNS tumor growth.

It is also advisable not to use glutamine in patients with seizure disorders, since in rare cases it may increase the excitotoxin glutamate, exacerbating pre-existing seizure tendencies (the author has observed this on several occasions clinically).

Although it is common to give glutamine on an empty stomach, it is here recommended to be administered with at least a small amount of food, to avoid digestive upset.

In general, glutamine has a high safety margin in the dog. The author doses glutamine once a day according to the following dosing schedule.

Glutamine-dosing.png


4. Silymarin
Silymarin is a well-known family of compounds commonly extracted from the milk thistle. Often-used veterinary supplements containing silymarin include Denamarin® and Apocaps®. Denamarin® has been shown to moderately reduce hepatopathy secondary to lomustine.

Silymarin also has protective effects on the kidneys, heart and CNS.

Silymarin dosing
The author uses both Denamarin® and Apocaps® as labeled, given with a small amount of food to reduce the incidence of digestive upset.

5. Ubiquinone (CoQ10)
Cumulative cardiac toxicity is a concern with common chemotherapy drugs such as doxorubicin. CoQ10 has been shown to ameliorate cardiotoxicity and has not been shown to reduce the efficacy of conventional therapy.

The most common potential side effect of CoQ10 in dogs is digestive upset, which can be minimized by administering it with a small amount of food.

CoQ10 dosing
CoQ10 is dosed at 1 mg per pound of body weight once daily, or in divided doses. This supplement is fat soluble and more effective if given at the same time as an oil, such as an omega-3 fish oil supplement.

6. Antioxidants
The use of antioxidants during chemotherapy and radiation is hotly debated. On one side, there is concern that as a group they may interfere with some chemotherapies and radiation. The other side of the argument stipulates that chemotherapy, radiation, as well as cancer itself, increase harmful free radical loads and that antioxidants are therefore good for cancer treatment.

To make the issue cloudier still, antioxidants when viewed as a functional group are very diverse, and have remarkably different net effects. Furthermore, a given antioxidant can have the opposite effect (become pro-oxidant), depending on the dose and circumstance. Finally, the various effects of these compounds above and beyond their redox activity may be more clinically relevant than their antioxidant effects.

Simply speaking, the balance of current research shows that, as a group, dietary levels of antioxidants may help cancer patients recover better from surgery, chemotherapy and radiation, improve their life expectancy, and increase longevity. Minimally, harm has not been shown in review. The author, therefore, supports dietary antioxidant intake during chemotherapy and radiation.

Conclusion
Including side effect mitigation strategies as standard of care is beneficial in canine cancer treatment. Early implementation of these therapies can potentially address adverse consequences of both canine cancer and its treatment. This aids in establishing a sane, compassionate balance between patient life quality and longevity.

Editor’s note:

If you are interested in learning more about Dr. Dressler’s approach to managing canine cancer, he has created a private video training series, sponsored by Functional Nutriments, that is free to veterinarians. You can find it at http://FunctionalNutriments.com/IVC.

Disclosure statement:

The author of this publication developed the Apocaps® formula and is a paid consultant for Functional Nutriments, LLC. He has no equity interest in either Functional Nutriments, LLC or Apocaps®.

References
Metronomic chemotherapy

Gaspar TB, Henriques J, Marconato L, Queiroga FL. “The use of low-dose metronomic chemotherapy in dogs — insight into a modern cancer field”. Vet Comp Oncol. 2018 Mar;16(1):2-11.

Biller B. “Metronomic chemotherapy in veterinary patients with cancer: rethinking the targets and strategies of chemotherapy”. Vet Clin North Am Small Anim Pract. 2014 Sep;44(5):817-29.

Maiti R. “Metronomic chemotherapy”. J Pharmacol Pharmacother. 2014;5(3):186-92.

Galbraith EA, McKellar QA. “Pharmacokinetics and pharmacodynamics of piroxicam in dogs”. Vet Rec. 1991 Jun 15;128(24):561-5.

Knapp DW, Richardson RC, Chan TC, Bottoms GD, Widmer WR, DeNicola DB, Teclaw R, Bonney PL, Kuczek T. “Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder”. J Vet Intern Med. 1994 Jul-Aug;8(4):273-8.

Rao CV. “Regulation of COX and LOX by curcumin”. Adv Exp Med Biol. 2007;595:213-26. Review.

Daily JW, Yang M, Park S. “Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials”. J Med Food. 2016;19(8):717-29.

Deng YI, Verron E, Rohanizadeh R. Molecular “Mechanisms of Anti-metastatic Activity of Curcumin”. Anticancer Res. 2016 Nov;36(11):5639-5647. Review.

Vallianou NG, Evangelopoulos A, Schizas N, Kazazis C. “Potential anticancer properties and mechanisms of action of curcumin”. Anticancer Res. 2015, Feb;35(2):645-51. Review.

Benavente-García O, Castillo J, Alcaraz M, Vicente V, Del Río JA, Ortuño A. “Beneficial action of citrus flavonoids on multiple cancer-related biological pathways”. Curr Cancer Drug Targets. 2007 Dec;7(8):795-809. Review.

Meiyanto E, Hermawan A, Anindyajati. “Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents”. Asian Pac J Cancer Prev. 2012;13(2):427-36. Review.

Wu CP, Ohnuma S, Ambudkar SV. “Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy”. Curr Pharm Biotechnol. 2011;12(4):609-20.

Cordyceps

Zhu R, Chen YP, Deng YY, et al. “Cordyceps cicadae extracts ameliorate renal malfunction in a remnant kidney model”. J Zhejiang Univ Sci B. 2011;12(12):1024-33.

Tuli HS, Sandhu SS, Sharma AK. “Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin”. 3 Biotech. 2013;4(1):1-12.

Hsieh CF, Chang HC, Huang SL, Chen CL, Chen WT, Yang CC. “Prescribed Renoprotective Chinese Herbal Medicines Were Associated with a Lower Risk of All-Cause and Disease-Specific Mortality among Patients with Chronic Kidney Disease: A Population-Based Follow-Up Study in Taiwan”. Evid Based Complement Alternat Med. 2017;2017:5632195.

Wang Y, Yin H, Lv X, Wang Y, Gao H, Wang M. “Protection of chronic renal failure by a polysaccharide from Cordyceps sinensis”. Fitoterapia. 2010 Jul;81(5):397-402.

Ong BY, Aziz Z. “Efficacy of Cordyceps sinensis as an adjunctive treatment in kidney transplant patients: A systematic-review and meta-analysis”. Complement Ther Med. 2017 Feb;30:84-92.

Peng Y, Chen Q, Yang T, Tao Y, Lu X, Liu C. “Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice”. Mol Biol Rep. 2014 Mar;41(3):1815-27.

Chen M, Cheung FW, Chan MH, Hui PK, Ip SP, Ling YH, Che CT, Liu WK. “Protective roles of Cordyceps on lung fibrosis in cellular and rat models”. J Ethnopharmacol. 2012 Sep 28;143(2):448-54.

Yang L, Jiao X, Wu J, et al. “Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease”. Exp Ther Med. 2018;15(3):2731-2738.

Wang N, Li J, Huang X, Chen W, Chen Y. “Herbal Medicine Cordyceps sinensis Improves Health-Related Quality of Life in Moderate-to-Severe Asthma”. Evid Based Complement Alternat Med. 2016;2016:6134593.

Liu WC, Wang SC, Tsai ML, Chen MC, Wang YC, Hong JH, McBride WH, Chiang CS. “Protection against radiation-induced bone marrow and intestinal injuries by

Cordyceps sinensis, a Chinese herbal medicine”. Radiat Res. 2006 Dec;166(6):900-7.

Liu WC, Chuang WL, Tsai ML, Hong JH, McBride WH, Chiang CS. “Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia”. Exp Biol Med (Maywood). 2008;233(4):447-55.

Nakamura K, Shinozuka K, Yoshikawa N. “Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis”. J Pharmacol Sci. 2015 Jan;127(1):53-6.

Song J, Wang Y, Teng M, et al. “Cordyceps militaris induces tumor cell death via the caspase-dependent mitochondrial pathway in HepG2 and MCF-7 cells”. Mol Med Rep. 2016;13(6):5132-40.

Glutamine

Noé JE. “L-glutamine use in the treatment and prevention of mucositis and cachexia: a naturopathic perspective”. Integr Cancer Ther. 2009 Dec;8(4):409-15.

Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. “Prevention of chemotherapy and radiation toxicity with glutamine”. Cancer Treat Rev. 2003 Dec;29(6):501-13. Review.

Gaurav K, Goel RK, Shukla M, Pandey M. “Glutamine: A novel approach to chemotherapy-induced toxicity”. Indian J Med Paediatr Oncol. 2012;33(1):13-20.

Rao R, Samak G. “Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions”. J Epithel Biol Pharmacol. 2011;5(Suppl 1-M7):47-54.

Noé JE. “L-glutamine use in the treatment and prevention of mucositis and cachexia: a naturopathic perspective”. Integr Cancer Ther. 2009 Dec;8(4):409-15.

Gaurav K, Goel RK, Shukla M, Pandey M. “Glutamine: A novel approach to chemotherapy-induced toxicity”. Indian J Med Paediatr Oncol. 2012;33(1):13-20.

Niklison-Chirou MV. “Glutamine metabolism, the Achilles heel for medulloblastoma tumor”. Cell Death Dis. 2018;9(2):74. Published 2018 Jan 22.

Oizel K, Chauvin C, Oliver L, Gratas C, Geraldo F, Jarry U, Scotet E, Rabe M, Alves-Guerra MC, Teusan R, Gautier F, Loussouarn D, Compan V, Martinou JC, Vallette FM, Pecqueur C. “Efficient Mitochondrial Glutamine Targeting Prevails Over Glioblastoma Metabolic Plasticity”. Clin Cancer Res. 2017 Oct 15;23(20):6292-6304.

Ramadan S, Lin A, Stanwell P. “Glutamate and glutamine: a review of in vivo MRS in the human brain”. NMR Biomed. 2013;26(12):1630-46.

Silymarin

Skorupski KA, Hammond GM, Irish AM, Kent MS, Guerrero TA, Rodriguez CO, Griffin DW. “Prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy in tumor-bearing dogs”. J Vet Intern Med. 2011 Jul Aug;25(4):838-45.

Razavi BM, Karimi G. “Protective effect of silymarin against chemical-induced cardiotoxicity”. Iran J Basic Med Sci. 2016;19(9):916-923.

Dashti-Khavidaki S, Shahbazi F, Khalili H, Lessan-Pezeshki M. “Potential renoprotective effects of silymarin against nephrotoxic drugs: a review of literature”. J Pharm Pharm Sci. 2012;15(1):112-23. Review.

CoQ10

Conklin KA. “Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity”. Integr Cancer Ther. 2005 Jun;4(2):110-30. Review.

Greenlee H, Shaw J, Lau YI, Naini A, Maurer M. “Lack of effect of coenzyme q10 on doxorubicin cytotoxicity in breast cancer cell cultures”. Integr Cancer Ther. 2012;11(3):243-50.

Antioxidants

Conklin KA. “Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects”. Nutr Cancer.

2000;37(1):1-18. Review.

Gröber U, Holzhauer P, Kisters K, Holick MF, Adamietz IA. “Micronutrients in Oncological Intervention”. Nutrients. 2016;8(3):163. Published 2016 Mar 12. doi:10.3390/nu8030163.

Sak K. :Chemotherapy and dietary phytochemical agents”. Chemother Res Pract. 2012;2012:282570.
 

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