Cancer Outline



Chinese Herbal Treatment of Cancer in Small Animals: the Blood Moving Formulas

Steve Marsden

DVM ND MSOM LAc. Dipl.CH AHG CVA

Introduction

Clinical trials in Chinese herbal medicine have disclosed repeatedly that only when a treatment is suited from both a biomedical and Chinese medical perspective will it work.

In Chinese medical parlance, many tumors arise from so-called Blood stasis. This metaphoric interpretation of a tumor is easy to understand. A precondition for a tumor to become clinically significant and metastatic is its ability to stimulate angiogenesis. Grossly, this vessel growth is disorganized, resulting in tortuous varicosities that certainly resemble stagnant blood. In addition, angiogenesis is much more likely to occur in areas that are relatively hypoxic because of poor perfusion. Not surprisingly, then, the herbs that were empirically observed to be most utile in managing these tumors and that inherited the title of Blood Movers have significant ability to inhibit angiogenesis as well as locally and regionally manipulate and optimize circulation.

Crucial main formulas to address this mechanism of tumor development, together with their most common clinical manifestations, are listed in Figure 1 below. The Blood Moving formulas are amongst the easiest for veterinarians to learn to use effectively in the treatment of cancer amongst their patients.

Figure 1 Blood stasis formulas and their indications

|Formula |Region |Indications |

|Xue Fu Zhu Yu Tang |Chest |Pulmonary neoplasia |

| | |Thyroid adenocarcinoma |

| | |Salivary adenocarcinoma |

| | |Hemangioma |

| | |Thymic adenocarcinoma |

| | |Cutaneous mast cell tumors (grades I to III) |

|Ge Xia Zhu Yu Tang |Abdominal tumors |Prostatic adenocarcinoma |

| | |Some cases of hemangiosarcoma |

| | |Hepatic adenocarcinoma |

|Xian Fang Huo Ming Yin |Appendicular tumors |Melanoma |

| | |Squamous cell carcinoma |

|Shao Fu Zhu Yu Tang |Caudal abdomen |Transitional cell carcinoma |

| | |Renal adenocarcinoma |

Dose

Formulas contain hundreds of chemical compounds all of which work in synergy. As a result formulas are never dosed according to their content of just one compound. Likewise, their activity does not depend on the presence or absence of just one compound. Instead, all constituents work together synergistically to create coordinated physiological effects. Thus, when a larger number of ingredients is present in a formula, the dose does not automatically go up to, since a dilution of some ingredients is made up for by the addition of others.

The dose table provides a reliable starting dose for all the formulas that follow, regardless of their number of ingredients. Liquid versions are available from Kan Herb, and granular extracts available from Natural Path Herb Company. A Time to Heal Herbs distributes for both companies, and can be reached via atthherbs@

The names of these formulas are generic, meaning other companies make versions besides Kan and Natural Path. Dr. Marsden has an advisory role in both Kan and Natural Path regarding their particular versions of these formulas, and can thus speak reliably to the dosing of their products. For other versions, please contact the manufacturer for their dose recommendations.

|Weight (kg) |Weight (lbs) |Liquid BID Dose (mls) |Granule BID Dose |

| | | |(tsp) |

|4 |10 |0.30 | 1/4 |

|8 |20 |0.50 | 3/8 |

|12 |25 |0.50 | 1/2 |

|23 |50 |1.00 | 3/4 |

|32 |70 |2.00 |1 |

|65 |150 |3.00 |1 1/2 |

|120 |250 |4.00 |2 |

Minor Bupleurum

Before launching into a more detailed discussion of the Blood Moving formulas, it is important to spend time discussing a real workhorse of Chinese herbal treatments for cancer. It is powerfully anti-neoplastic agent in its own right, has inspired the development of many successful derivatives, and can help potentiate the action of many formulas, particularly the Blood Movers discussed below. It should be included as an inclusion in most of the protocols where the formulas below are also being used.

The formula contains:

|Chai Hu |Bupleurum root |

|Ban Xia |Pinellia rhizome |

|Gan Cao |Licorice root |

|Sheng Jiang |Ginger rhizome |

|Da Zao |Jujube |

|Ren Shen |Ginseng root |

|Huang Qin |Scutellaria root |

• Indications

o Use concomitantly with any of the formulas listed below, particularly for:

▪ Hemangiosarcoma

▪ Prostatic adenocarcinoma

▪ Pulmonary neoplasia

▪ Thyroid adenocarcinoma

• Mechanism

o Induce apoptosis

o Inhibit angiogenesis

o Stimulate the immune system

o Kill many types of cancer cells

o Inhibit lymphocyte mitogenesis in the spleen

• Side Effects

o Avoid use in patients with chronic renal failure due to non-inflammatory renal conditions, signaled by urine protein creatinine ratios that are less than 3.0

o Avoid use by itself in patient with confirmed microhepatica and microvascular shunts

For hemangiosarcoma, some added components are essential for efficacy:

• Addition of Panax Notoginseng (San Qi) in significant quantity, or concomitant use of Yunnan Bai Yao, a patented hemostatic herb readily available from a large number of vendors

o Yunnan Bai Yao alone seems to permit hemangiosarcoma patients to exceed the typical three month survivals otherwise seen following splenectomy

o It does the same for nasal adenocarcinoma. Piroxicam and Yunnan Bai Yao together reliably producing survivals that rival the year that can be achieved by radiation therapy

• Use of a Blood moving herb (Chinese Angelica) or herbal formula, for example Ge Xia Zhu Yu Tang (below). For weakened patients, consider Astragalus and Ligustrum (Golden Flower brand)

• For actively hemorrhaging patients, use a derivative of Minor Bupleurum, instead, known as Chai Hu Jia Long Gu Mu Li Tang (Bupleurum, Dragon Bone and Oyster Shell Combination, Settle the Yang)

Xue Fu Zhu Yu Tang (Drive Stasis from the Mansion of Blood, Blood’s Palace, Dispel Stasis in the Palace of Blood)

From a Chinese medical perspective, one of the reasons that Blood can become stagnant is if Blood volume is low (so-called Blood deficiency), just as a river low in water breaks into stagnant pools.

Patients with Blood deficiency have impaired peripheral circulation, leading often to an assortment of dryness symptoms. In western terms, the impairment may come from anemia or from a centralization of the blood supply, particularly some from of pulmonary congestion.

In cancer cases, then, the formula is most helpful when:

• Increased immune surveillance is required to treat or prevent peripheral and cutaneous tumors, or

• Angiogenesis and/or pulmonary congestion is occurring due to tumor activity within the chest cavity

The constituents of Xue Fu Zhu Yu Tang, a formula in use since the 19th century, are as follows:

|Tao Ren |Persica seed |

|Dang Gui Shen |Chinese Angelica root |

|Hong Hua |Carthamus flower |

|Chuan Niu Xi |Cyathula root |

|Sheng Di Huang |Rehmannia root |

|Chi Shao |Red Peony root |

|Zhi Ke |Bitter Orange |

|Chuan Xiong |Ligusticum rhizome |

|Jie Geng |Platycodon root |

|Chai Hu |Bupleurum root |

|Gan Cao |Licorice root |

Therapeutic effects are enhanced when a modified version of the formula containing Curcuma is used. Natural Path sells this as Modified Xue Fu Zhu Yu Tang while Kan sells it as Dispel Stasis in the Palace of Blood. Curcuma possesses marked anti-neoplastic activity, acting through a number of different pathways. It inhibits:

• Apoptosis

• Angiogenesis

• Protein kinases (which convert mitogenic stimuli into actual cell division events)

• Metastasis

The overall effect is an increase in peripheral circulation at the expense of pulmonary circulation. Increased cutaneous circulation appears to enhance immune surveillance of the skin, helping to control mast cell tumor development.

• Indications

o Poor peripheral and hepatic circulation might be characterized by:

▪ Cool extremities or ears

▪ Dry skin

▪ Superficial pyoderma (mild)

▪ Mild to moderate liver enzyme elevations

▪ Normocytic normochromic non-regenerative anemia

▪ Weak pulses

o Pulmonary congestion or neoplasia might be indicated by:

▪ Lavender tongue

▪ Chronic hacking or resonant cough

▪ Dyspnea

o Specific tumors

▪ Recurrent cutaneous mast cell tumor (grade III or lower)

▪ Thymic adenocarcinoma

▪ Hemangioma

▪ Pulmonary metastases of most tumors

▪ Salivary adenocarcinoma

▪ Thyroid adenocarcinoma

▪ Anal gland adenocarcinoma

• Mechanism

o Bone marrow stimulation through the actions of Chinese Angelica and Rehmannia

o Pulmonary decongestion with increased peripheral blood flow

o Immune stimulation

o Cytotoxicity to cancer cells

o Anti-tussive effect through bronchodilation

• Side Effects

o If the patient has latent tendencies toward acute inflammatory bowel disease, these may be mildly activated, producing loose stools

o If the patient has tendencies toward acute hepatitis, these may be activated, unless Minor Bupleurum is used simultaneously

Ge Xia Zhu Yu Tang (Drive Stasis from Below the Diaphragm Decoction, Dispel Stasis in the Middle Palace, Angelica and Corydalis Combination)

Ge Xia Zhu Yu Tang (Drive Stasis from Below the Diaphragm Decoction) is indicated for Blood Stasis manifesting within the abdomen rather than the chest. Examples include prostatic adenocarcinoma, hepatic adenocarcinoma, and some cases of hemangiosarcoma.

Its constituents are listed below:

|Dang Gui |Chinese Angelica |

|Chuan Xiong |Ligusticum |

|Chi Shao Yao |Red Peony |

|Zhi Ke |Bitter Orange |

|Gan Cao |Licourice |

|Xiang Fu |Cyperus |

|Wu Yao |Lindera |

|Mu Dan Pi |Moutan |

|Tao Ren |Persica |

|Hong Hua |Carthamus |

|Wu Ling Zhi |Pteropus |

|Yan Hu Suo |Corydalis |

The formula contains anodyne herbs such as Corydalis and Lindera, making it a good match for the abdominal pain that typically accompanies hepatic adenocarcinoma. The net vascular effect of the formula, like Xue Fu Zhu Yu Tang, is to move Blood away from the tumor, thus disrupting angiogenesis and promoting oxidation.

• Indications may include:

o Very high liver enzyme elevations

o Cranial abdominal masses and pain

o Irritability

o Restlessness

o Depression

o Red or purple-red tongue

o Specific tumors

▪ Prostatic adenocarcinoma

▪ Hepatic adenocarcinoma

▪ Hemangiosarcoma

o For prostate and liver tumors, use with Minor Bupleurum

o For splenic tumors, use with Minor Bupleurum and Curcuma

• Mechanism

o The formula contains many of the same herbs as Xue Fu Zhu Yu Tang above, resulting in it having many of the same core anti-neoplastic properties, including:

▪ Immune stimulation

▪ Cancer cell cytotoxicity

• Side Effects

o Avoid use in animals with microhepatica and microvascular shunts

Shao Fu Zhu Yu Tang (Drive Blood Stasis from the Lower Abdomen Decoction, Dispel Stasis in the Lower Palace, Fennel and Corydalis Combination)

Shao Fu Zhu Yu Tang is indicated for Blood stasis tumors of the lower abdomen, especially renal neoplasia, prostatic adenocarcinoma and transitional cell carcinoma.

It contains:

|Dang Gui |Chinese Angelica |

|Chuan Xiong |Ligusticum |

|Chi Shao Yao |Red Peony |

|Xiao Hui Xiang |Fennel |

|Rou Gui |Cinnamon |

|Gan Jiang |Ginger |

|Yan Hu Suo |Corydalis |

|Mo Yao |Myrrh |

|Pu Huang |Bulrush pollen |

The formula is a powerful smooth muscle antispasmodic, by virtue of its content of Ginger, Fennel, Peony and Cinnamon, that makes it well matched to spasmodic disorders, such as cystitis, and urethritis from prostatitis. Bulrush and Angelica have significant hemostatic properties, making it useful for severe hematuria from renal adenocarcinoma.

The type of Blood stasis addressed by this formula is said in Chinese medicine to be due to Cold Coagulation. The abdomen is considered to have become so cold as to congeal blood, often causing significant pain. Such abdominal cold conditions are considered to be more common in geriatric patients

• Indications

o Hematuria, whether acute or chronic

o Abdominal pain

o Chronic cystitis

o Colitis in geriatric patients (see below)

o Tenesmus

o Constipation

o Abdominal lymphadenopathy from metastasis

o Geriatric symptoms, including

▪ Chilliness

▪ Hind end weakness

▪ Urinary incontinence

▪ Low energy

o Cancers

▪ Transitional cell carcinoma

▪ Prostatic adenocarcinoma

▪ Renal adenocarcinoma

▪ Anal gland adenocarcinoma (metastatic to the abdominal lymph nodes)

• Mechanism

o For more severely inflamed bladder tumors, combine use with Four Marvels Combination

• Side Effects

o None of note

Xian Fang Huo Ming Yin (Angelica and Mastic Combination, Sublime Joint Formula)

Literally translated, Xian Fang Huo Ming Yin means Sublime Formula for Sustaining Life, so-named because of its antimicrobial effects traditionally applied to the treatment of abscesses. Abscesses are similar in Chinese medicine to cancer, since both conditions can involve inflammation and perturbations of blood flow. Clinical signs that can be seen in both conditions which the formula addresses include inflammation, ulceration and bleeding. Specific examples include squamous cell carcinoma and malignant melanoma of the digits, as well as osteosarcoma of the equine.

It contains:

|Bei Mu |Thunbery Fritillaria bulb |

|Dang Gui Wei |Chinese Angelica root tips |

|Bai Zhi |Angelica root |

|Chi Shao |Red Peony root |

|Mo Yao |Myrrh |

|Ru Xiang |Mastic (Boswelia) |

|Gua Lou Gen |Trichosanthes root |

|Zao Ci |Gleditsia spine |

|Chen Pi |Citrus peel |

|Fang Feng |Ledebouriella root |

|Gan Cao |Licorice root |

|Jin Yin Hua |Honeysuckle flower |

• Indications

o Consider Xian Fang Huo Ming Yin for any peripheral or superficially located neoplasms that appear purulent or infective

o It can even be applied topically (in granule form, mixed into a salve) for any ulcerative tumor regardless of type. Examples include mastocytoma and cutaneous lymphoma

• Mechanism

o Boswelia contributes important anti-neoplastic effects, including:

▪ Inhibition of cell invasion

▪ Promotion of cell differentiation

▪ Inhibition of angiogenesis

o Myrrh promotes cell differentiation and apoptosis

o Honeysuckle is anti-infective

• Side Effects

o None of note

In addition, Xian Fang Huo Ming Yin is excellent post-operatively for speeding wound healing in the limbs following surgical removal of these tumors.

Nutritional Supplementation in Cancer Patient Management

The following is a summary of the anti-cancer effects of various vitamins, minerals, and supplements. In general, vitamins and minerals are best supplemented in combination with each other to promote optimal absorption and utilization.

In addition to being an antioxidant with an ability to protect regulatory genes from deactivation, Vitamin A is the chief agent in the body that promotes cell differentiation and apoptosis, and has cytotoxic effects on certain tumors. The dose recommended, based on animal and human studies, is equivalent to 625-7500IU/lb/day. High doses of vitamin A have the reputation for toxicity, especially when given for periods of weeks to months at a time, but most dogs and cats seem much more tolerant of vitamin A than veterinarians generally presume. For example, 5000 IU/lb/day is a dose routinely prescribed by the author for several months at a time, but without any apparent side effects or toxicity. Occasional type I hypersensitivity reactions to preservatives, manifesting chiefly as hives, have been observed in some individuals receiving vitamin A injections. These reactions are not seen when the same preparation is administered orally. Injectable products seem to be absorbed easily when given orally. Each drop contains approximately 10,000 IU of vitamin A, sufficient for a 2 lb dog for one day.

One means of obtaining the benefits of vitamin A in promoting cell differentiation without using toxic doses may be to use vitamin A in tandem with other agents that either promote cell differentiation by themselves, or assist vitamin A in this action. DHA, commonly found in commercial omega-3 fatty acid preparations for the treatment of skin disease, is known to enhance the cell differentiating effect of vitamin A.

Vitamin D3 has a major effect on promoting cell differentiation, but also may inhibit tumor growth, angiogenesis and metastasis, according to animal studies. The doses used in these studies are toxic, however, leading to hypercalcemia. Vitamin D is often included with vitamin A in injectable preparations; the above doses for vitamin A seem to result in levels of vitamin D that are safe, presumably because vitamin D must be hydroxylated first to become activated, producing a metabolic bottle neck that limits its actual toxicity.

Vitamin E and selenium are widely known for their antioxidant effects, but also may inhibit tumor growth. Selenium even has cytotoxic effects on some cancer cells. Vitamin E is given at a rate of 10 IU/lb daily. The dose for selenium in animals is 2-5 mcg/lb daily.

Omega-3 fatty acids have a well established role in cancer management. Dozens of animal studies suggest that they inhibit tumor growth and metastasis, inhibit cachexia, and may increase effectiveness of some chemotherapy drugs. These studies have investigated eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are contained in fish oil. Other sources of omega-3 fatty acids have been recommended, such as flaxseed oil, but these contain alpha-linolenic acid (ALA). ALA is converted at low efficiency to EPA and DHA by humans, but probably not converted by dogs or cats. An empirical dose of fish oil is 180mg EPA and 120mg DHA (contained in a regular strength capsule in 1000mg of fish oil) per 5-10lbs of animal. DHA, as a component of an omega-3 fatty acid preparation, is recommended to be prescribed at doses of up to 24mg per lb body weight daily. If the animal develops signs of Damp accumulation at this high dose, supplement at the highest level tolerated.

Flavonoids (or bioflavonoids): are contained in a wide range of medicinal and food plants. These include flavones (luteolin, apigenin), isoflavones (daidzein, genistein), flavonols (quercetin, kaempferol), flavanols (tea catehcins) and anthocyanidins/proanthocyanidins. The various compounds may have antioxidant, estrogenic, antiestrogenic, anti-metastatic and cytotoxic effects. Proanthocyanidin dose is approximately 20-60mg/lb daily. Flavonol, flavone and isoflavonoid doses range from 15-50 mg/lb daily or more. Generally, flavones seem to act as Blood moving agents.

A popular supplement for use in cancer management is inositol hexaphosphate (IP6, phytate). It may exert an anti-cancer effect by altering signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and tumor suppressor genes. In vitro and animal studies suggest a role in treatment of carcinomas and leukemias particularly. Empirical dose is 10-50mg/lb daily.

Other Anti-Cancer Herbs

Other herbs can be given singly to animals or mixed in their food, in addition to the formula most appropriate for their diagnosis.

Garlic appears to have antioxidant, immune-enhancing and eicosanoid mediated mechanisms that are active in treatment of cancer. The toxic dose for garlic is not well established in dogs and cats, although the potential for Heinz body anemia after acute high doses or chronic use is well recognized. There does appear to be an individual susceptibility to garlic toxicity, but veterinarians have used doses of approximately 1 clove per 50 lbs of dog, and 1/8 - 1/4 clove for cats. Some practitioners use the extract product Kyolic at 10-30mg/lb daily.

Curcumin, a yellow pigment from the spice, turmeric, inhibits tumor growth and metastasis, reduces side effects of chemotherapy and may increase the action of some chemotherapy agents, as well as preventing cancer. The suggested dose is 15 to 20mg/lb daily.

Green tea (Camellia sinensis) may inhibit tumor growth, angiogenesis and metastasis, in addition to preventing cancer. Dried green tea can be mixed in food at the highest dose the animal will tolerate. Standardized green tea extract contains a constant amount of epigallocatechin gallate, which can be dosed at 5 mg/lb daily.

Contrary to expectations, studies assessing the impact of Milk Thistle on outcomes of conventionally treated patients revealed that those receiving the herb as a supplement had superior responses to chemotherapy and radiation. Milk Thistle slows metastasis by interfering with basement membrane penetration and subsequent tumor spread through angiogenesis. In addition to improving their efficacy, Milk Thistle is hepato-protective, serving to insulate the liver from damage by chemotherapy agents.

Ginger is a powerful anti-emetic, acting both centrally and peripherally to quell nausea even from highly toxic platinum-based drugs.

Mushroom extracts, for example from Ganoderma lucidum, are popular additions to anti-cancer protocols for animals. Their immune polysaccharides:

• Target angiogenesis

• Boost immune response

• Are cytotoxic to tumor cells

• Inhibit tumor cell invasion

• Can be used in any tumor protocol

For maintenance of appetite and reduction of nausea during chemotherapy, or in advanced cancer cases, consider Liu Jun Zi Tang (Six Gentlemen Combination, Six Gentle Pets):

|Bai Zhu |White Atractylodes rhizome |

|Fu Ling |Poria |

|Ban Xia |Pinellia rhizome |

|Ren Shen |Ginseng root |

|Chen Pi |Citrus peel |

|Gan Cao |Licorice root |

Dose is as for the other herbal formulas in these notes.

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