ࡱ> ?A89@ @ YbjbjVV 8r<r<QnnnnnnnJ\J\J\J\l\|>_(f_f_f_f_A`A`A`KMMMMMM$Rjqn fA`A` f fqnnf_f_KlKlKl f.nf_nf_KKl fKKlKl~annf_2_ [xJ\9iv^0=jNiNnnnnDNnA`a0KlcdA`A`A`qq$;?Al ?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  SEQ Figure \* ARABIC 1 Blood stasis formulas and their indications FormulaRegionIndicationsXue Fu Zhu Yu TangChestPulmonary neoplasia Thyroid adenocarcinoma Salivary adenocarcinoma Hemangioma Thymic adenocarcinoma Cutaneous mast cell tumors (grades I to III)Ge Xia Zhu Yu TangAbdominal tumorsProstatic adenocarcinoma Some cases of hemangiosarcoma Hepatic adenocarcinomaXian Fang Huo Ming YinAppendicular tumorsMelanoma Squamous cell carcinomaShao Fu Zhu Yu TangCaudal abdomenTransitional 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  HYPERLINK "mailto:atthherbs@aol.com" atthherbs@aol.com 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)4100.30 1/48200.50 3/812250.50 1/223501.00 3/432702.001 651503.001 1/21202504.002  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 HuBupleurum rootBan XiaPinellia rhizomeGan CaoLicorice rootSheng JiangGinger rhizomeDa ZaoJujubeRen ShenGinseng rootHuang QinScutellaria root Indications Use concomitantly with any of the formulas listed below, particularly for: Hemangiosarcoma Prostatic adenocarcinoma Pulmonary neoplasia Thyroid adenocarcinoma Mechanism Induce apoptosis Inhibit angiogenesis Stimulate the immune system Kill many types of cancer cells Inhibit lymphocyte mitogenesis in the spleen Side Effects 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 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 Yunnan Bai Yao alone seems to permit hemangiosarcoma patients to exceed the typical three month survivals otherwise seen following splenectomy 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, Bloods 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 seedDang Gui ShenChinese Angelica rootHong HuaCarthamus flowerChuan Niu XiCyathula rootSheng Di HuangRehmannia rootChi ShaoRed Peony rootZhi KeBitter OrangeChuan XiongLigusticum rhizomeJie GengPlatycodon rootChai HuBupleurum rootGan CaoLicorice 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 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 Pulmonary congestion or neoplasia might be indicated by: Lavender tongue Chronic hacking or resonant cough Dyspnea 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 Bone marrow stimulation through the actions of Chinese Angelica and Rehmannia Pulmonary decongestion with increased peripheral blood flow Immune stimulation Cytotoxicity to cancer cells Anti-tussive effect through bronchodilation Side Effects If the patient has latent tendencies toward acute inflammatory bowel disease, these may be mildly activated, producing loose stools 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 GuiChinese AngelicaChuan XiongLigusticumChi Shao YaoRed PeonyZhi KeBitter OrangeGan CaoLicouriceXiang FuCyperusWu YaoLinderaMu Dan PiMoutanTao RenPersicaHong HuaCarthamusWu Ling ZhiPteropusYan Hu SuoCorydalis 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: Very high liver enzyme elevations Cranial abdominal masses and pain Irritability Restlessness Depression Red or purple-red tongue Specific tumors Prostatic adenocarcinoma Hepatic adenocarcinoma Hemangiosarcoma For prostate and liver tumors, use with Minor Bupleurum For splenic tumors, use with Minor Bupleurum and Curcuma Mechanism 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 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 GuiChinese AngelicaChuan XiongLigusticumChi Shao YaoRed PeonyXiao Hui XiangFennelRou GuiCinnamonGan JiangGingerYan Hu SuoCorydalisMo YaoMyrrhPu HuangBulrush 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 Hematuria, whether acute or chronic Abdominal pain Chronic cystitis Colitis in geriatric patients (see below) Tenesmus Constipation Abdominal lymphadenopathy from metastasis Geriatric symptoms, including Chilliness Hind end weakness Urinary incontinence Low energy Cancers Transitional cell carcinoma Prostatic adenocarcinoma Renal adenocarcinoma Anal gland adenocarcinoma (metastatic to the abdominal lymph nodes) Mechanism For more severely inflamed bladder tumors, combine use with Four Marvels Combination Side Effects 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 MuThunbery Fritillaria bulbDang Gui WeiChinese Angelica root tipsBai ZhiAngelica rootChi ShaoRed Peony rootMo YaoMyrrhRu XiangMastic (Boswelia)Gua Lou GenTrichosanthes rootZao CiGleditsia spineChen PiCitrus peelFang FengLedebouriella rootGan CaoLicorice rootJin Yin HuaHoneysuckle flower Indications Consider Xian Fang Huo Ming Yin for any peripheral or superficially located neoplasms that appear purulent or infective 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 Boswelia contributes important anti-neoplastic effects, including: Inhibition of cell invasion Promotion of cell differentiation Inhibition of angiogenesis Myrrh promotes cell differentiation and apoptosis Honeysuckle is anti-infective Side Effects 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. 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