Canine Thyroid Carcinoma: Potential Role of Chinese Herbal Therapies in Patient Care

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This article is the intellectual property of Dr. Erin Bannink, August 2021.

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Perspectives on Integrative Patient Management with Chinese Herbal Therapies

Traditional Chinese Medicine (TCM) modalities are often implemented in my practice for management of thyroid cancer, usually in the gross disease setting when other treatments are declined or the patient is not a good candidate for standard-of-care treatment interventions. A thorough discussion of TCM differential diagnoses and treatment options is beyond the scope of this article. The goal here is to provide an introduction to the western biomedical understanding of some TCM herbs often used in management of thyroid cancer in my practice and how their clinical effects may be understood from a western biomedical standpoint.

Xiao Chai Hu Tang

Xiao Chai Hu Tang is used in my practice for management of various carcinomas including thyroid carcinoma in the gross disease setting. This formula contains Chai Hu (Bupleurum), for which saikosaponin-d is one of the major bioactive compounds. Saikosaponin-d has been shown to inhibit proliferation of human undifferentiated thyroid carcinoma cells in vivo via induction of G1-phase cell cycle arrest and induction of apoptosis. The compound was also shown to increase expression of cell suicide signals p53 and bax and decrease the cell survival signaling molecule Bcl-2 along with other molecular effects (Liu, 2014).

Modified Xue Fu Zhu Yu Tang

Modified Xue Fu Zhu Yu Tang is another TCM herbal formula that can be useful in management of thyroid carcinoma, both for local and metastatic disease. Visible partial disease regressions have been observed in my practice. This formula contains the following herbs: peach seed (Tao Ren), angelica root (Dang Gui), safflower flowers (Hong Hua), cyathula root (Chuan Niu Xi), rehmannia root (Sheng Di Huang), red peony root (Chi Shao), bitter orange (Zhi Ke), lovage root (Chuan Xiong), platycodon root (Jie Geng), bupleurum root (Chai Hu), licorice root (Gan Cao) with added curcuma (E Zhu) and sparganium (San Leng).

This formula also contains bupleurum (Chai Hu), some of whose anti-neoplastic actions have been introduced above under the information about Xiao Chai Hu Tang. Angelica root (Dang Gui) contains two compounds, decursin and decursinol, which have been shown to effectively inhibit VEGF-regulated angiogenesis and exhibiting anti-tumor activity in vivo, supporting these compounds as potential treatments for cancers dependent on VEGF signaling. Specifically, decursin inhibits VEGFR2 activation, a receptor involved in canine thyroid carcinoma progression (Jung, 2009; Lee, 2009; Son, 2009; Urie, 2012). Platycodin, a saponin present in Platyodon (Jie Geng), has been shown to inhibit EGFR activation via the PiK3/Akt pathway, a pathway also involved in canine thyroid carcinoma (Chun, 2013). Curcuma zedoaria (E Zhu) contains curcumin which has numerous anticancer actions based on hundreds of published studies, blocking over 500 molecules involved in tumor progression. Its molecular targets potentially relevant to thyroid carcinoma include NF-kB, Cox-2, and VEGF (Deng, 2012). The bioactive compound in sparganium (San Leng) which has shown anticancer action is Grailsine-Al-glycoside (Zhang, 2014).

These two formulas together, along with other herbal formulas, have been used to successfully manage a number of canine patients with non-resectable or metastatic thyroid carcinoma in my practice. While many promising anecdotes of positive response to herbal therapy in dogs with thyroid carcinoma can be recounted, well designed clinical trials will be important in elucidating the true efficacy of these treatments, expected response rates and accurate prognostication of expected survival times in comparison to conventional therapies. This will be particularly relevant in guiding treatment and referral discussions and informing alternative management options when conventional standard of care oncology treatments are declined or beyond the financial reach of clients. Following are two case examples from my practice.

Metastatic Thyroid Carcinoma in a Golden Retriever Managed with Herbal Therapies

An 8 year old male neutered Golden Retriever weighing 65 pounds, presented 1/5/2009 for oncology consultation. He had been recently adopted from a rescue organization and had a large cervical mass which was confirmed as a thyroid carcinoma on surgical biopsy performed 12/12/08. Pulmonary metastasis were present at that time. His new caregivers were primarily interested in palliative end of life care which would not carry risk of adversely affecting his quality of life. Chemotherapy was declined. Herbal therapies were elected and were initiated 1/19/2009 at which time the left sided thyroid tumor measured 6.5cm x 5cm x 6.5cm and progression of the pulmonary metastasis was documented on thoracic radiographs. Granular extract Xue Fu Zhu Yu Tang modified with E Zhu and San Leng ¾ tsp twice daily was prescribed. Granular extract Xiao Chai Hu Tang ¾ tsp twice daily was added 2 weeks later. Dose of both formulas was increased to 1 tsp twice daily 2/23/2009. Pulmonary lesions were stable on thoracic radiographs performed 4/21/2009 and remained stable on thoracic radiographs performed 9/12/2009.

Thoracic Radiographs (RDVM films) 1/5/2009 showed lung metastasis:

Progressive disease by 1/19/2009: Thoracic Radiographs at time of Consultation

Thoracic radiographs 4/21/2009 showed stable disease 3 months after starting herbal therapies:

Thoracic radiograph 9/12/2009 showed stable disease:

The patient was maintained on these herbal therapies with excellent quality of life and no respiratory signs until 12/16/2009 when he became acutely lethargic with increased respiratory effort. Thoracic radiographs showed a diffuse interstitial pattern most suggestive of pneumonia. The thyroid tumor was stable in size. He was treated with antibiotics and recovered for a short time. He was ultimately euthanized for respiratory signs presumed to be due to progressive lung metastasis about 1 year after his diagnosis. He experienced no gastrointestinal side effects or hematologic toxicity from his herbal treatments.

Functional Thyroid Carcinoma Managed with Integrative Therapies

An 11 year old female spayed husky mix weighing 63 pounds, presented 6/26/2012 for oncology consultation with history of a cervical mass first noted 3 months prior, polyuria, polydipsia and significant weight loss. T4 was elevated at 6.7 (reference range 0.8-4.0). Cytology of the 5cm x 5.5cm cervical mass was suggestive of thyroid carcinoma. Thoracic radiographs showed no evidence of lung metastasis. She was also diagnosed with junctional tachycardia with occasional second-degree AV block. She had changes on echocardiogram consistent with hyperthyroidism: hyperdynamic function and mild myocardial hypertrophy.

Surgery and radiation were declined. The patient was treated with methimazole 10mg twice daily. Herbal therapy consultation was pursued 7/10/2012. The thyroid tumor had increased in size to 6.7cm x 5.5cm x 3cm. Granular extract Liu Wei Di Huang Wan ½ tsp twice daily and granular extract modified Xue Fu Zhu Yu Tang ½ tsp twice daily were prescribed. A maitake mushroom D-fraction supplement was also started. Historical Deramaxx 25mg daily was continued. She was started on a balanced home cooked diet.

The patient presented for a recheck 7/31/2012 at which time her energy level had markedly improved, polyuria and polydypsia had resolved and the thyroid tumor was stable in size at 6.5cm x 4cm x 4cm. By 8/21/2012 the tumor had decreased slightly in size to 5.5cm x 4.3cm x 3cm.

The tumor was larger (7.5cm x 5cm x 4.5cm) at her visit 9/18/2021 at which time Liu Wei Di Huang Wan was stopped, granular extract Si Wu Tang ½ tsp twice daily was started and modified Xue Fu Zhu Yu Tang dose was increased to ¾ tsp twice daily, resulting in tumor shrinkage to 5.5cm x 4.5cm x 3cm by 10/9/2012.

She continued methimazole and herbal management of her cancer with adjustments including Xiao Chai Hu Tang and Chai Hu Jia Long Gu Mu Li Tang until 4/30/2013 at which time Palladia was started due to progressive disease (8.5cm x 6.5cm x 6cm tumor dimensions). The tumor gradually decreased in size to 5cm x 4cm by 4/1/2014. Her thyroid tumor remained stable on these treatments until the time of her death.

The patient developed unilateral epistaxis 12/2/2014 and was diagnosed with a suspected nasal tumor based on clinical signs and physical exam. CT imaging was declined. Herbal treatment adjustments were made to support quality of life and control epistaxis. She was euthanized 2/18/2015 due to uncontrollable epistaxis. Her thyroid cancer was still stable with no evidence of lung metastasis at the time of her death.

The patient survived 2 years 11 months after her diagnosis of functional thyroid carcinoma. CBC and Chemistry panel were monitored monthly to bi-monthly throughout the course of her treatment. She had no gastrointestinal and hematologic toxicity from her integrative therapy protocol.

Chun J, Kim YS. Platycodin D inhibits migration, invasion and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways. Chem Biol Interact 2013 Oct 5;205(3):212-21.

Deng S, Hu B, Shen KP, et al. Inflammation, macrophage in cancer progression and chinese herbal treatment. J Basic Clin Pharm 2012 Mar;3(2):269-72.

Jung MH, Lee SH, Ahn EM, et al. Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway. Carcinogenesis 2009 Apr;30(4):655-61.

Lee HJ, Lee HJ, Lee EO, et al. In vivo anti-cancer activity of Korean Angelica gigas and its major pyranocoumarin decursin. Am J Chin Med 2009;37(1):127-42.

Liu RY, Li JP. Saikosaponin-d inhibits proliferation of human undifferentiated thyroid carcinoma cells through induction of apoptosis and cell cycle arrest. Eur Rev Med Pharmacol Sci 2014;18(17):2435-43.

Son SH, Kim MJ, Chung WY, et al. Decursin and decursinol inhibit VEGF-induced angiogenesis by blocking the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. Cacner Lett 2009 Jul 18;280(1):86-92.

Urie BK, Russell DS, Kisseberth WC, et al. Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelets derived growth factor receptors-alpha and –beta, KIT and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma. BMC Vet Res 2012 May 25;8:67.

Zhang JW, Wei TH. Anti-cancer effects of Grailsine-Al-glycoside isolated from Rhisoma Sparganii. BMC Complement Altern Med 2014 Mar 3;14:82.