Integrated approaches to canine cancer: Mitigation of treatment side effects

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Integrated approaches to canine cancer: Mitigation of treatment side effects

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.

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.

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®.

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