Complementary and Alternative Therapies in Veterinary Oncology

The internet is a boon for salespeople who capitalize on the fears and hopes of owners of pets with cancer. Typically these claims lack data from controlled clinical trials showing safety and efficacy, and because the substances are not regulated as drugs, they are not required to be produced according to GLC so contamination and inconsistent potency are relatively common problems. Once data showing safety and efficacy is available for any particular substance, it becomes part of “mainstream” medicine.

 

Common products that pet owners find are Tumexal, EBC-46, Apocaps, K9 Immunity, K9 Transfer factor, and wormwood products (Artemisinin), which all lack data showing they are either bioavailable in dogs and / or safe or effective (other than what is on their websites). We cannot say if they work or not, because it has never been scrutinized in any sort of clinical trials (despite the hundreds to thousands of dogs they claim to have used it on) – it’s all anecdote and testimonials.

 

Drugs like K-Vax and EBC-46 have publications that purport to show efficacy, but often the tumours were not biopsied, and efficacy is poorly defined relying on “doing better than expected”, rather than actual improvement in survival or tumour control. Localized necrosis (as reported with EBC-46) is not an indication of anticancer effectiveness, and may lead to severe complications (see bloodroot below).

 

There are little published data on most of the "alternative" medicines. It is also very difficult to identify any potential toxicity, as most patients are receiving multiple different types of supplement, which confuses the issues. Other compounds may cause toxicity; for example, although rare, xiao-chai-hu-tang is documented to cause acute hepatic disease. This is a single case report, but so is the “efficacy” on which it is being prescribed for many patients.  It also has been associated with interstitial pneumonitis. Some direct experience we have had is that some of our patients also receive Five Mushroom Extract; used in the assistance of treatment for cancer and chemotherapy for “immune support”; consisting of various Chinese Mushrooms, including Cordyceps, Shitake; Reishi; Tremella. We had one patient that developed severe and acute liver toxicity and possible gastric ulceration that continued despite stopping chemotherapy but then resolved after ceasing the alternative medications (but there were approximately 20 of them so it’s not possible to identify the actual causative agent), and those signs did not recur when chemotherapy was restarted.

 

In dogs with lymphoma, the only study published so far has been for Maitake mushroom as a treatment. There was no decrease in lymph node size (objective response) seen in any of the dogs. Thirteen dogs developed progressive disease before the 4th week. Another study investigated Coriolus versicolor (Yun-Zhi) for dogs with haemangiosarcoma, and claimed improved survival in the abstract, but in the article, the improvement in survival was not significant statistically, and was based on 5 dogs; there was no discussion about tumour grade (which markedly affects survival).

 

An interesting statistic to consider when thinking about where the new “cures” for cancer come from is that between 1990 and 2005, there were 920 anticancer compounds that underwent clinical trials (so these are ones that got beyond the initial testing of in vitro and mice testing and into human subjects) in the USA. Of these only 32 were found to be effective. Many got as far as late-stage clinical testing before being found to be ineffective. It is important to remember this when evaluating whether to recommend untested "alternative" drugs, where the likelihood of finding true benefit is probably no greater than for traditional drugs; in other words, it would have only a 3.5% chance of actually benefiting patients, but without the testing and analysis that we require “conventional" drugs to go through, we will never know which of the alternative medications might work.

 

Separate to that is the question of “supplements” to reduce the toxicity of chemotherapy. In truth we do a good job of this with antiemetics and antibiotics, so unless there is a specific problem with an individual patient’s chemotherapy, we are not sure there is an advantage to adding more chemicals (even if “natural”).

 

However, we totally understand that owners wish to try anything that may help their pet, and we try to support them in safely and sensibly pursuing whatever other avenues feel right to them. Many of our patients do also receive complementary and alternative treatments in addition to their conventional treatments. The problem is that there are many unscrupulous salespeople out there ready to prey on these people – and a plethora of “offerings” - so they need a lot of help to sort out what is what. This phenomenon isn’t new of course, the internet just makes it easier.

 

If they really want to pursue complementary and alternative treatments they would be better off going to see a veterinarian specially trained in that area. We do ask people to avoid antioxidant supplements with chemotherapy, as they can interfere with the mode of action of chemotherapeutics and reduce efficacy.

 

We have found one of the best explanations of our concerns in a veterinary website, voiced by

SkeptVet; http://skeptvet.com/Blog/2014/03/tumexal-wonder-drug-of-snake-oil/.

 

The Cancer Council of Australia has released a booklet called “Understanding Complementary Therapies that your clients may want to have a look at (http://www.cancercouncil.com.au/1987/b1000/complementary-therapies-40/understanding-complementary-therapies-using-therapies/?pp=74162&cc=4233&&ct=35).

 

For more aggressive opposing views there is http://www.quackwatch.org/ , although the veterinary portion is fairly small.

 

 

A few selected abstracts follow.

 

Comparison of high-dose intermittent and low-dose continuous oral artemisinin in dogs with naturally occurring tumors. J Am Anim Hosp Assoc. 2014;50:390-5. Hosoya K, Couto CG, London CA, Kisseberth WC, Phelps MA, Dalton JT.

 

To evaluate the clinical toxicity and activity of orally administered artemisinin in dogs with spontaneous tumors, 24 client-owned dogs were randomly divided into  two groups and received either low-continuous dose (3 mg/kg q 24 hr) or high-dose intermittent (three doses of 45 mg/kg q 6 hr repeated q 1 wk) of artemisinin per  os. Treatment was continued for 21 days. Dogs were evaluated weekly for clinical  effect and at the end of the treatment for hematologic and biochemical adverse events. Whole blood concentrations of artemisinin and dihydroartemisinin were measured by liquid chromatography/tandem mass spectrometry after the first dose of artemisinin in three dogs in each group. Blood concentrations of artemisinin and dihydroartemisinin were <0.1 μM at all time points, and there was no difference in blood concentration between the two dosing groups. The most frequent adverse event was anorexia, which was observed in 11% of the low-dose group and 29% of the high-dose group. Oral artemisinin, both in low-dose continuous and high-dose intermittent, is well tolerated in dogs but results in low bioavailability. Parenteral administration should be considered for future studies.

 

Consequences of intratumoral injection of a herbal preparation containing blood root (Sanguinaria canadensis) extract in two dogs. J Am Vet Med Assoc. 2011;239:374-9. Childress MO, Burgess RC, Holland CH, Gelb HR.

 

CASE DESCRIPTION: 2 dogs were referred for surgical removal of cutaneous tumors that had previously been treated by intratumoral injection of a herbal preparation containing blood-root (Sanguinaria canadensis) extract.

CLINICAL FINDINGS: 11 days following injection of bloodroot extract into a small dermal tumor, dog 1 developed a large, soft, fluctuant cutaneous mass at the site of injection. Ultrasonographic evaluation of the mass revealed a fluid-filled central cavity with increased echogenicity of the surrounding subcutaneous tissues. Dog 2 had a small dermal tumor under the left mandible that had been treated in similar fashion. However, an exuberant reaction was not observed following injection of bloodroot extract in this dog.

TREATMENT AND OUTCOME: Both dogs underwent surgical excision of the cutaneous tumors. Histologic evaluation revealed severe necrosis and inflammation in the excised tissues from dog 1. This dog experienced postsurgical wound complications and had a prolonged postsurgical recovery. Similar, although less severe, histopathologic findings were apparent in the excised tissues from dog 2; this dog recovered without complications.

CLINICAL RELEVANCE: Various products containing bloodroot are marketed on the Internet for topical and parenteral treatment of cutaneous neoplasms in domestic animals. However, the antineoplastic properties, therapeutic efficacy, and adverse effects of these products are poorly described in the veterinary literature. Clinicians should be aware of the potential for harm caused by the use of these products.

 

 

Mushroom-derived maitake PETfraction as single agent for the treatment of lymphoma in dogs. J Vet Intern Med. 2007;21:1409-12. Griessmayr PC, Gauthier M, Barber LG, Cotter SM.

 

BACKGROUND: Maitake PETfraction is a standardized essence extracted from the mushroom Maitake (Grifola frondosa) that has antitumor activity in tumor-bearing mice. In addition, PETfraction induces apoptosis in human prostate and bladder cancer cells and suppresses the proliferation in vitro of several canine tumor cell lines, such as lymphoma (Cl-1), mammary gland (CF33), and connective tissue (CF21).

HYPOTHESIS: Maitake PETfraction is effective as a single agent in dogs with lymphoma.

ANIMALS: Fifteen dogs with confirmed intermediate or high-grade lymphoma were enrolled into this prospective, noncontrolled, clinical trial. Inclusion criteria were an expected survival time of at least 2 weeks and no major organ dysfunction.

METHODS: Maitake PETfraction was administered at a dose of 3 drops/kg/day divided into 2 doses given 1 hour before feeding. Dogs were evaluated by physical examination with tumor measurement, body weight, CBC, and chemistry profile before treatment and after 2, 4, 8, and 12 weeks. At each visit, owners completed a questionnaire addressing overall quality of life, appetite, and any adverse effects noted.

RESULTS: A decrease in lymph node size of greater than 50% (objective response) was not seen in any of the dogs. Thirteen dogs developed progressive disease before the 4th week. The median treatment duration was 27 days (range, 9-228).

PETfraction was well accepted, and minimal adverse effects were observed. Two dogs developed hyphema. It was not known if this was related to progressive lymphoma or was an adverse effect of treatment.

CONCLUSIONS: No objective responses were observed to administration of Maitake PETfraction, and the drug was well tolerated in these dogs.

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Veterinary Oncology Consultants
379 Lake Innes Drive
Lake Innes, NSW 2446
Australia

voc@vetoncologyconsults.com

+61 (2) 6585 3192