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Home > Newsletters > January 2008 > Chinese Medicine and Cancer Care - Page 5

Chinese Medicine and Cancer Care - Page 5

By Efrem Korngold, LAc, OMD and Harriet Beinfield, LAc

Research Investigations

A literature review performed in 1998 by the University of Texas Center for Alternative Medicine Research in Cancer summarized many Chinese studies, including controlled trials with human subjects, animal, and in vitro laboratory experiments.55 The studies showed the impact of medicinal herbs on: disease response, survival outcome, immune response, reduction in adverse effects from chemotherapy and radiation, improved recovery from surgery, better quality of life, and alleviation of
pain. This review indicated that some patients who received Chinese herbal medicine combined with conventional Western treatment demonstrated significantly better survival and/or disease response than patients receiving Western treatment alone. But often research design has involved inadequate methodology, including the absence of randomized, placebo or blinded controls. While the examples that follow hardly constitute proof of efficacy, they are suggestive of benefit, indicating that further research is desirable and necessary.

For example, in a study of 76 patients with second-stage primary liver cancer there were no 5-year survivors in the groups treated with chemotherapy or radiation alone, whereas there was a 10% survival in the group treated with a combination of Fu Zheng herbs and radiation, and a 16.7% survival in those treated with both herbs and chemotherapy.56 Five-year survival rates in another study of patients with liver cancer who received chemotherapy alone were 6%, whereas when combined with the herb formula Si Jun Zi Tang (Panax ginseng, Atractylodes macrocephela, Poria cocos, Glycyrrhiza uralensis), 5-year survival rose to 43%.57

Herbs that are qi and yang tonifying, that warm and strengthen the spleen and kidney, are thought to ameliorate the adverse effects of chemotherapy and radiation. Zhang Xinqi comments, “The leukopenia caused by chemotherapy or radiotherapy is classified as a deficiency type of illness which is referred to as the morbid condition showing deficiency of genuine qi, lowered body resistance, and declining of function. Then, supplementing qi and nourishing the blood, warming and
invigorating the spleen and kidney are the essential therapeutic principles for remitting toxic side effects.”58 

Two of the important toxin-removing herbs used in cancer therapy are Sophora flavescens (ku shen, meaning bitter root of miraculous effect) and Sophora subprostrata (shan dou gen), containing matrine and oxymatrine series alkaloids that show cytotoxic activity in vitro and antitumor activity in vivo, (inhibit the growth of sarcoma-180 in laboratory mice). Oxymatrine itself is 7.8 times stronger than the chemotherapeutic agent mitomycin C in its tumor inhibiting effects, without suppressing the
immune system.59 Sophora flavescens (or subprostrata) also increases leukocytes and promotes peripheral immune responses. Scutellaria baicalensis (huang qin) is another potent heat and toxin-clearing herb with anti-tumor and immune-stimulating properties in vivo and, in vitro, that inhibits platelet aggregation and induces apoptosis.60 And another herb, Isatis tinctoria (ban lan gen) contains the compound indirubin, observed by Chinese scientists to exert an effect against chronic myelocytic leukemia (CML). It inhibits DNA synthesis in neoplastic cells, particularly
immature leukemic cells in bone marrow, while simultaneously stimulating immune response.61

Angelica sinensis (dang gui) is a blood supplementing and activating herb with anti-tumor, immune stimulating, and antiangiogenic properties that reduces vascular permeability in vitro.62 Other potent herbs in the blood activating category with direct cancer-inhibiting properties are Curcuma zedoaria (e zhu), Salvia miltiorrhiza (dan shen), and Panax pseudoginseng (tian qi). These herbs are fibrinolytic, antithrombic, and anti-inflammatory. People with cancer often have elevated fibrinogen levels, increasing the stickiness of the blood so that it is more likely to
coagulate. Because the “sticky” factors in blood facilitate the adherence of metastatic cells to healthy tissue, and because tumors are often encapsulated within a tough fibrin coating difficult for anti-neoplastic drugs or immune cells to penetrate, herbs that increase microcirculation, make the blood less viscous, the fibrin coating more permeable, and soften and disperse masses. When extracts of curcuma are injected in mice with tumors, the tumors shrink.63

Enhancing Conventional Protocols

To overcome the adverse effects while at the same time potentiating the desired effects of conventional treatment, a popular biological response modifying formula called All Inclusive Great Tonifying Decoction (Shi Quan Da Bu Tang) is often used. It appears to restore hematopoeitic function to improve peripheral blood counts, and increases interleukin production along with NK cells. This formula contains Panax ginseng (ren shen),
Angelica sinensis (dang gui), Poria cocos (fu ing), Atractylodes macrocephela (bai zhu), Astragalus membranaceus (huang qi), Ligusticum wallichii (chuan xiong), Peonia lactiflora (bai shao),
prepared
Rehmannia glutinosa (shu di huang), Cinnamomum cassia (rou gui),
and prepared Glycyrrhiza uralensis (zhi gan cao). It was found to potentiate the therapeutic activity of chemotherapy (Mitomycin, Cisplatin, Cyclophosphamide, Fluorouracil) and radiotherapy, inhibit recurrence, prolong survival, and prevent or ameliorate adverse treatment effects such as: anorexia, nausea, vomiting, hematotoxicity, immuno-suppression, leukopenia, thrombocytopenia, anemia, and nephropathy.

In traditional terms, the herbs Panax ginseng (ren shen), prepared Glycyrrhiza uralensis (gan cao), Poria cocos (fu ling), and Atractylodes macrocephala (bai zhu) tonify qi, while Angelica sinensis (dang gui), Ligustici wallichii (chuan xiong), Peonia lactiflora (bai shao), and prepared Rehmannia glutinosa (shu di huang) nourish the blood, and Astragalus membranaceus (huang qi) and Cinnamomum cassia (rou gui) further invigorate qi and yang.64 In another study to determine effects of this formula on white blood cell counts, 134 patients with cancer who had previously undergone chemotherapy and radiation therapy that resulted in
leukopenia were given the formula and 113 patients experienced an increase of white blood counts to normal levels.65 In a study of 58 patients with osteogenic sarcoma who were receiving either Cisplatin and Dexamethasone (CD) or high-dose Methotrexate and Vincristine (MV), patients were randomly assigned to the herbal arm or observation. Those using the herb formula in the MV group experienced improvements in white blood cell and platelet counts and there was less transaminase enzyme elevation. Both the CD and MV groups showed improvement in posttherapy cardiac function, less nausea and vomiting, and fewer rashes than those in the control group.66

Whereas tumor recurrence for post-surgical patients with bladder cancer was 65% with conventional treatment alone, this was reduced to 33% when patients added the use of the Chinese medicinal mushroom Polyporus umbellatus (zhu ling or maitake in Japanese).67 In another study, those receiving radiation alone suffered from low white blood cell and platelet counts, but this was reversed in subjects who received Chinese herbs: 40 patients recovered from 3450/c.mm to 5425/c.mm,
whereas in the control group without herbs, white blood cell counts dropped significantly.68

Five-year survival for advanced nose and throat cancer patients receiving radiation alone was 24% whereas adding the herbal formula Yi Qi Yang Yin Tang to the conventional protocol produced a 52% five-year survival.69 In a study of 197 patients with stage III and IV nose and throat cancers, half received radiation in combination with the formula Yi Qi Yang Yin Tang and half received only radiotherapy. After 3 years the survival rates
were 67% and 33% respectively. This formula is targeted to nourish the qi and fluids as well as clear heat and toxins and eliminate blood stagnation.70 In yet another study of this formula for nasopharyngeal cancer, 272 patients were treated with radiation, half of whom received the formula. In the herb-treated group, 5-year relapse was 68% lower (12 % versus 38%), and survival rates were also significantly improved (67% versus 48% at 5-years).71

In 285 patients with lymph node metastases, one group received only chemotherapy with no significant tumor shrinkage; another received only herbal medicine with only 12% showing significant shrinkage; whereas in the group that received chemo, radiation, and herbs, or radiation plus herbs, 75% showed significant tumor shrinkage.72 When 70 patients with
chronic gastritis and dysplasia were divided in groups according to traditional Chinese pattern diagnosis (hyperactive liver qi, deficiency cold of the spleen and stomach, deficiency of stomach yin, and damp heat in the spleen and stomach) and treated accordingly, 84% markedly improved, 4% responded partially, and 11% were unresponsive.73

A study at Drew University in Los Angeles investigated the effects of medicinal mushrooms on patients with advanced malignancies: in 2 weeks there were marked decreases in tumor associated antigens and marked increases in natural killer cell activity in 8 out of 11 subjects.74 In another study, patients with primary liver carcinoma who received herbs in combination with chemotherapy had increased numbers of NK cells.75

A study of 176 patients compared half the subjects who received injections of Astragalus membranaceus (huang qi) and Panax ginseng (ren shen) while undergoing chemotherapy for colon cancer, to a control group that was not administered herbal injections. Those receiving the herbal injections had higher white blood cell counts, greater macrophage activity, and increased body weight.76 A study of the herb astragalus at MD Anderson Hospital and Tumor Institute in Houston, Texas confirmed earlier reports by the same authors that this herb possesses immuno-potentiating activity, correcting in vitro T-cell function deficiency found in many cancer patients. Decades of pharmacological research have
revealed that the polysaccharides and other compounds in Astragalus membranaceus promote cellular (intensifies phagocytosis) and humoral (increases function of B lymphocytes) immune function and have in vitro anti-tumor effects on cancer cell lines.77 Research at MD Anderson Hospital in Houston reproduced these results in a 1983 study, demonstrating that aqueous extracts of Astragalus membranaceus in vitro and in vivo enhanced levels of circulating lymphocytes. A second study in 1988 confirmed and expanded the previous findings that extracts of Chinese herbs possess potent immune restorative activity. A polysaccharide fraction of Astragalus membranaceus (fraction 3, F-3) was isolated as most potent. The data indicated that extracts of astragalus could restore T-cells from immune compromised cancer patients to normal levels of function.78 In a human trial, Astragalus membranaceus was found to potentiate IL-2 tenfold, permitting a smaller, less toxic
effective dose, restoring T-cell function in 9 out of 10 cancer patients.79 Whereas the common dose of Astragalus membranaceus is 9 to 30 grams of dried herb for non-cancerous conditions, doses as high as 60 grams per day may be administered as an immunostimulant. Although toxicity is low at high doses, occasionally symptoms of over-stimulation such as insomnia, increased heart rate, palpitations, or hypertension can occur at these high doses.80

Multiple studies on patients with stomach cancer were conducted using the formula Pishen Fang ( Jian Pi Yi Shen) that supplements qi and yang, has immuno-stimulating properties, and contains: Codonopsis pilolusa (dang shen), Atractylodes macrocephala (bai zhu), Lycium barbarum (gou qi zi), Ligustrum lucidum (nu zhen zi), Cuscuta chinensis (tu si zi), and Psoralea corylifolia (bu gu zhi). One study examined 81 patients with stage III gastric cancer who received chemotherapy. Those who also took the herbal formula experienced improved digestive and bone marrow function, as well as increased survival. In the herbal group, 5-year survival
was 46% compared to 20% in the chemotherapy-only group.81 In another study, 669 late-stage gastric cancer patients who were receiving chemotherapy were randomly divided into the herbal arm, and the control group. Improvements in body weight, appetite, reduced nausea and vomiting, were observed in the group that received the formula. White blood cell counts were 7% in the herb-treated group compared to 33% in the control group. Macrophage activity was 21% greater in the treated group, and 5-year survival among 303 stage III and 63 stage IV patients
who received follow-up were 53% and 10% respectively. After 10 years, 47% of the stage III patients remained alive.82 Another study examined 216 postoperative stomach cancer patients at stage III, and 110 patients at stage IV, showing that of the half who did not receive the herbal formula, 75% were able to finish the complete chemotherapy course, compared to 95% who received the herbs. Patients in the herb-treated group gained weight (23% vs. 8%); fewer lost weight (6% vs. 14%); fewer lost their appetite (10% vs. 32%); and fewer had vomiting (4% vs. 12%).83,84

In an animal study, Mitomycin C showed a stronger antitumor effect when combined with ginseng.85 Similarly, when an extract of the mushroom Polyporous umbellatus (zhu ling) was combined with Mitomycin C, the life span of tumor-bearing mice was increased by 119.9%, compared to 70% in the control group treated with the drug alone.86 Ginsenosides, the active saponin compounds in the ginsengs, increase phagocytosis,
appetite, blood formation, accelerate the biosynthesis of DNA, and appear to induce cancer cells to change their morphology and become more like healthy cells. The polysaccharides in Astragalus membranaceus (huang qi) and Panax ginseng (ren shen) and medicinal mushrooms regulate T-cells and stimulate interferon and phagocytosis, producing both immune-restorative and cancer-inhibiting effects.

An herbal formula used to relieve signs of cardiac distress (palpitation, irregular, small and slow pulse, occasional premature systole, lower-wall myocardial ischemia) secondary to treatment with Adriamycin (doxorubicin), is called Zhi Gan Cao Tang, or Baked Licorice Decoction, consisting of 20 gm Glycyrrhiza uralensis (gan cao), 30 gm Rehmannia glutinosa (di huang), 30 pieces Ziziphus jujuba (da zao), 15 gm Zingiberis officinale (jiang), 15 gm Cannabis indica (huo ma ren), 10 gm Panax ginseng (ren shen), and 10 gm Cinnamomum cassia (gui zhi) administered as a decoction. When cardiac function normalized after 6 days, Adriamycin therapy resumed, and administration of the decoction
was continued.87

Another prescription developed in modern times, is a formula described in 1982 by Dr Hong-Yen Hsu containing Wisteria sinensis (zi teng), Terminalia chebula (he zi), Trapa bispinosa (ling jiao), and Coix lachryma-jobi (yi yi ren).88 Both Wisteria sinensis (he zi) and Trapa bispinosa (ling jiao) have a history of use in China and Japan for the treatment of tumors.
Coix lachryma-jobi (yi yi ren) and Terminalia chebula (he zi) have been used traditionally to strengthen digestive and respiratory functions as well as to relieve infection and inflammation.89 Coix lachryma-jobi is now considered a general anti-cancer agent. This prescription conforms to the principles of invigorating qi and strengthening resistance (improving digestive and respiratory function) and clearing heat and eliminating toxins (removing infection and inflammation).

The US Food and Drug Administration approved the first Chinese-made anti-cancer drug for Phase II clinical human trials in 2001, to be conducted by the US biopharmaceutical company, Oncoherb. The drug, called Kanglaite injection, is an extract distilled from the seeds of the herb Coix lachryma-jobi (yi yi ren). It has demonstrated efficacy against lung cancer in clinical trials with over 200,000 cancer patients conducted in China. Studies have indicated that it may also be useful in the treatment of other types of cancer, including stomach and cervical cancers, and solid tumors. The preliminary findings of research conducted in the US support the Chinese trials. The new drug significantly improves the efficacy of radiation therapy and chemotherapy treatments in late-stage, lung cancer patients. It is far less toxic than existing chemotherapeutic agents and is effective in patients for whom existing treatments did not show any improvements.90

In the November 2001 issue of Life Sciences, Henry Lai from the University of Washington reported on the cytotoxic activity of artemesinin, a compound from Artemesia annua (quing hao). Artemesinin kills human breast cancer cells in vitro by interfering with their iron metabolism. It was first discovered to be an effective anti-malarial agent in chloroquine-resistant cases. Malarial parasites depend on high iron concentrations for reproduction, as do cancer cells, and any micro-organisms. Excess iron
is associated with increased cancer notes. Breast cancer cells have
up to 15 times more transferrin receptors than healthy cells. Acute leukemia and pancreatic cancers have also been responsive to this agent in vitro, with no apparent adverse effects upon healthy tissue. The Breast Cancer Fund in San Francisco is supporting this research. Earlier studies showed that Artemesia annua and capillaries have direct cytotoxic effects in vivo without causing immunosuppression.91

While Debu Tripathy was an oncologist at the University of California at San Francisco (UCSF), he conducted an on-going placebo-controlled randomized trial for women with breast cancer, using a formula containing 21 Chinese herbs to investigate the alleviation of common side effects of chemotherapy, namely nausea, vomiting, fatigue, marrow suppression, risk of infection, and hair loss.92

Safety and Herb-Drug Interactions

Herb safety and herb-drug interactions are complex and controversial issues. With the increasing use of herbs by Westerners has come legitimate concern for potential abuse and toxicity. The safety of a drug, herb, or food is always relative and contextual. Safety is determined by defining the conditions under which a substance is considered to be safe or dangerous, and weighing potential benefits against possible short and long-term adverse effects. Herb-drug interaction is a similar puzzle: all
substances that enter the body interact with each other, ultimately affecting all body processes. The issue again is determining the benefit or detriment of such interactions.

Compared to the record of approved pharmaceutical drugs, with a few well-known exceptions such as Aconitum carmichaelie (fu zi), Cinnabaris (zhu sha), Aristolochia fangchi (guang fang ji), and Ephedra sinica (ma huang), Chinese medicinal herbs are safer.93 Aconite contains aconitine, a recognized poison, that is traditionally detoxified by boiling and then
combined with other herbs such as Zingiberis officinale (jiang), Ziziphus jujuba (da zao), and Glycyrrhiza uralensis (gan cao) that further mitigate its toxicity, yielding important therapeutic benefits. For example treated Aconite is combined with Panax ginseng in the treatment of acute cardiac failure. Cinnabaris, a crude ore, contains mercuric oxide and although considered unsafe by American standards, is still utilized in small doses in China for the short-term treatment of acute mental agitation without negative consequences. Many Aristolochia species have recently been shown to exert carcinogenic effects when used continuously for longer than 6 months, yet these species continue to be used in China with good results in the treatment of cancer and nephropathy, the very conditions for which they have been considered causative agents in the West. Ephedra
sinica (ma huang)
has appropriately been used as an anti-asthmatic,
antitussive diaphoretic and vasodilating component of numerous pulmonary and anti-arthritic formulas for centuries.

In the US over the past two decades, Ephedra has been inappropriately
marketed over-the-counter as a natural energy and weight loss stimulant, resulting in incidences of high blood pressure, palpitations, agitation, and insomnia. It is unfortunate that abuse and misuse have caused herbs such as these to become less available to professional health care providers, and have cast a dark shadow over the credibility and safety of Chinese medicinal herbs in general.

The hundreds of herbs that are in common use in China and the West are rarely associated with adverse effects that are not easily reversible. These effects are seldom serious and include such transient reactions as: nausea, indigestion, diarrhea, headache, dizziness, hot flashes, chills, and rashes that are rapidly abated by discontinued use or dose reduction. The preponderance of evidence shows that when used as an adjunct to
conventional medicine, Chinese herbs both enhance the desired effects and mitigate the harmful ones.

Sophisticated monitoring with biological testing, sterilization, and spectrographic analyses by manufacturers in the United States is insuring that herbal products are free of chemical contaminants, adulterants, pathogens, and substitutions. This heightened awareness along with stringent standards is encouraging Chinese manufacturers to adopt the good manufacturing practices (GMP) required by the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC).

There is a paucity of data that describes the interactions between pharmaceutical agents, and even less between herbs and drugs. A few herbs and foods have well understood interactions with drugs. Tetracycline absorption can be impeded by milk-based foods, whereas grapefruit juice increases the blood volume of certain drugs (antidepressants, antihistamines, antihypertensive) by inhibiting a drug-metabolizing enzyme (cytochrome P450). Hypericum perforatum (St. John’s Wort, tian ji huang) reduces blood levels of protease inhibitors by increasing their metabolism, while potentiating the effects of MAO and SSRI antidepressants by elevating seratonin levels. Green vegetables high in Vitamin K can oppose the blood-thinning action of drugs like
Heparin, Coumadin, or Warfarin. Because Gingko biloba (yin guo ye),
Salvia miltiorrhiza (dan shen)
and Angelica sinensis (dang gui) promote
microcirculation and inhibit platelet aggregation, they can potentiate the effects of anti-coagulants, as can Allium sativum (garlic)(da suan) and Zingiberis officinale (ginger, jiang). Astragalus membranaceus (huang qi), because of its immuno-stimulating properties, may counter the immunosuppressive action of anti-rejection drugs like Cyclosporin. In high doses, Glycyrrhiza uralensis (licorice)(gan cao) can mimic the action of cortisol, elevating blood pressure and increasing fluid retention.94 These findings are based on the use of these herbs as single agents.

When Angelica sinensis is incorporated into a formula such as Shi Quan Da Bu Tang, which supplements qi and blood and activates circulation, its hematopoietic properties are enhanced and its anticoagulant properties are reduced by the inclusion of herbs such as Rehmannia glutinosa (di huang) and Peonia lactiiflora (bai shao), making it an effective treatment for the anemia, bruising, and bleeding caused by radiation and chemotherapy. One of the side effects of standard anti-coagulant therapy is anemia. To solve this problem with Chinese medicine, the herbs Panax pseudoginseng (tian qi) and Millettia reticulata (ji xue teng) are used because of their triple hematopoietic, circulation-activating, and anti-hemorrhagic properties. Glycyrrhiza uralensis (licorice, gan cao) is ubiquitous, appearing in countless formulas in part because of its ability to modulate adrenal function. For example, the Decoction of Bupleurum chinense (chai hu) and Poria cocos (fu ling, Chai Ling Tang) contains many herbs, including Glycyrrhiza uralensis (gan cao), and is used to aid in the withdrawal from corticosteroid dependence.95

Rather than suggesting that people stop eating grapefruit or green vegetables, new information is broadening our understanding of the complexity of drug-food and drug-herb combinations, enhancing our ability to make prudent choices. Biologist Subhuti Dharmananda, PhD, suggests, “Herb-drug interactions may be minimized by having patients take the herbs and drugs at different times (one hour apart to avoid direct interaction in the digestive tract; 1.5 hours to avoid maximum blood levels of drug and herb at the same time). The dosage of herbs that are aimed therapeutically at the same function as the drugs (eg both are sedatives; both are hypoglycemics; both are anti-coagulants) should be reduced to
alleviate concerns about additive or synergistic effects that are too great. A certain level of additive effects might be desired in cases where the drug therapy is not producing the desired response.”96

Fundamentally, Chinese medicine is concerned with the behavior of qi. Consequently, all of the major modalities of Chinese medicine (acupuncture, herbal medicine, dietetics, qi gong) are employed to provoke the qi to reorder itself once a pathological process has begun and, ideally, before it has become clinically manifest. While Chinese medicine has developed its own sophisticated repertoire of treatments for specific diseases, its primary emphasis is ultimately upon restoring and preserving the healthy function of the body.

Acknowledgments

The authors wish to thank John Boik, Subhuti Dharmananda, PhD,
Stephen Cowan, MD, Ken Rose, Mary Tagliaferri, LAC,MD, Debu Tripathy, MD, Issac Cohen, LAC, and Larry Baskind, MD, for their help in contributing to this article. This article honors Elisabeth Targ, MD, and the mysteries.

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