ScienceDaily (Oct. 26, 2009) — Antioxidant extracts of the leaves of the Gingko biloba tree may protect cells from radiation damage, according to a study published in the International Journal of Low Radiation. The discovery may one day be used to help reduce side effects in cancer patients undergoing radiotherapy.

Chang-Mo Kang of the Korea Institute of Radiological and Medical Sciences in Taegu and colleagues are interested in the protective effects of well-known herbal remedies of which Gingko biloba is one. G. biloba is a unique tree species with no close living relatives and extracts of its leaves contain antioxidant compounds including glycosides and terpenoids known as ginkgolides and bilobalides.

These compounds are thought to protect cells from damage by free radicals and other reactive oxidizing species found in the body. These are generated continuously by the body’s normal metabolism, and in excess in some diseases or after exposure to pollution or radiation. They damage proteins, DNA and other biomolecules and left unchecked can kill cells.

As such, extracts of certain plants that contain antioxidants, including G. biloba, have attracted interest for their pharmacological activity. G. biloba is currently sold as a herbal supplement and there are numerous claims for health benefits, including the possibility of preventing the onset of dementia or Alzheimer’s disease.

Kang and colleagues have now collected human white blood cells, lymphocytes, from healthy donors aged 18 to 50 years. They treated half of these cells with commercially available G. biloba extract in the laboratory and doused the other half with salt solution as an experimental control. They then compared the effects of gamma radiation from radioactive cesium on the white blood cells compared to the untreated control samples.

The team uses a light microscope to look for lymphocytes undergoing programmed cell death, or apoptosis, as a result of radiation exposure. They found that there was a significant increase in apoptosis in the untreated cells compared with those treated with G. biloba extract. Almost a third of the untreated cells underwent apoptosis compared with approximately one in twenty of the treated cells. Parallel studies with laboratory mice also demonstrated a similar protective effect against radiation poisoning.

The results suggest that the extracts can neutralize the free-radicals and oxidizing agents produced in the cells by the radiation and so prevent them from undergoing apoptosis.

1. Shin et al. Protective effect of Gingko biloba against radiation-induced cellular damage in human peripheral lymphocytes and murine spleen cells. International Journal of Low Radiation, 2009; 6 (3): 209 DOI: 10.1504/IJLR.2009.028889

ScienceDaily (Sep. 29, 2008) — Gecko is a Chinese traditional medicine. It has definite effect on malignant tumor, especially on digestive system tumor. The incidence and mortality of tumor keep ascending all over the world. However, there was no study on the pharmacological studies of Gecko and its mechanisms of anti-tumor action remained unclear.

Now a research group in China has found that Gecko powder can inhibit EC9706 and EC1 growth and proliferation.

Gecko can also decrease vascular endothelin growth factor and basic fibroblast growth factor expression in tumor tissue and induce tumor cell apoptosis.

As is known, the effect on anti-tumor of traditional Chinese medicine (TCM) is related to more pathways and more targets. Most studies on action mechanisms of TCM in anti-tumor showed that TCM could inhibit tumors though supporting the healthy energy and strengthening the body resistance.

The research team, led by Prof. Wang from Henan University of China, showed that Gecko could not only reinforce immunity of organism but also induction of tumor cell apoptosis and the down-regulation of protein expression of VEGF and bFGF.

Chemotherapy, one of the major methods to treat cancer in Western medicine at present, has a poor selectivity and strong toxic and side effects, thus influencing its anticancer effect. In the past 40 years, Chinese experts have gained remarkable achievements in cancer treatment by integrating TCM with chemotherapy. This article gives us pharmacological studies of Gecko about antitumor and thus may provide foundation for its effective constituent.

1. Liu et al. Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice. World Journal of Gastroenterology, 2008; 14 (25): 3990 DOI: 10.3748/wjg.14.3990

ScienceDaily (Dec. 31, 2008) — Medicinal plants have been used as traditional remedies for hundreds of years. Among them, S. barbata has been traditionally used in treatment of hepatitis, inflammation, osteomyelitis and gynecological diseases in China. Studies indicate that extracts from S. barbata have growth inhibitory effects on a number of human cancers. Reports are available on the treatment of lung, breast and digestive system cancer, hepatoma, and chorioepithelioma with S. barbata extracts.

However, the underlying mechanism of the antitumor activity of S. barbata extracts remains unclear.

A research team led by Dr. Zhi-Jun Dai from the Medical School of Xi’an Jiaotong University studied the growth inhibitory effects of S. barbata and determined its mechanism of antitumor activity in mouse liver cancer cell line H22.

They found that ESB could inhibit the proliferation of H22 cell in a time dependent manner. Among the various phases of cell cycle, the percentage of cells in S phase was significantly decreased, while the percentage of cells in G1 phase was increased. Flow cytometry assay also showed ESB had positive effect on apoptosis. Typical apoptotic morphology such as condensation and fragmentation of nuclei and blebbing membrane of the apoptotic cells could be observed through transmission electron microscope and fluorescence microscope. Further investigating the molecular mechanism behind ESB-induced apoptosis, cells treated with ESB underwent a rapid loss of mitochondrial transmembrane potential(delta psi m), release of mitochondrial cytochrome c into cytosol, induction of caspase-3 activity in a dose-dependent manner. This may offer new evidence for S. barbata in the treatment of hepatoma in clinical practice.

1. Dai ZJ, Wang XJ, Li ZF, Ji ZZ, Ren HT, Tang W, Liu XX, Kang HF, Guan HT, Song LQ. Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3. World J Gastroenterol, 14(48): 7321-7328

ScienceDaily (Oct. 18, 2009) — A series of studies have demonstrated that Chrysanthemum indicum possesses antimicrobial, antiinflammatory, immunomodulatory, and neuroprotective effects. Recently, much attention has been devoted to the anticancer activity of Chrysanthemum indicum, especially in hepatocellular carcinoma (HCC). However, its anticancer mechanism of action is still not clear and needs further investigation.

A research article to be published on September 28, 2009 in the World Journal of Gastroenterology addresses this question. The research team, led by Prof. Zong-fang Li from the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, investigated the effects of Chrysanthemum indicum extract (CIE) on inhibition of proliferation and on apoptosis, and the underlying mechanisms, in a human HCC MHCC97H cell line.

They examined viable rat hepatocytes and human endothelial ECV304 cells by trypan blue exclusion and MTT assay, respectively, as normal controls. The proliferation of MHCC97H cells was determined by MTT assay. The cellular morphology of MHCC97H cells was observed by phase contrast microscopy. Flow cytometry was performed to analyze cell apoptosis with annexin V/propidium iodide (PI), mitochondrial membrane potential with rhodamine 123 and cell cycle with PI in MHCC97H cells. Apoptotic proteins such as cytochrome C, caspase-9, caspase-3 and cell cycle proteins, including P21 and CDK4, were measured by Western blotting.

The results showed CIE inhibited proliferation of MHCC97H cells in a time- and dose-dependent manner without cytotoxicity in rat hepatocytes and human endothelial cells. CIE induced apoptosis of MHCC97H cells in a concentration-dependent manner, as determined by flow cytometry. The apoptosis was accompanied by a decrease in mitochondrial membrane potential, release of cytochrome C and activation of caspase-9 and caspase-3. CIE arrested the cell cycle in the S phase by increasing P21 and decreasing CDK4 protein expression.

The researchers drew a conclusion that CIE exerted a significant apoptotic effect through a mitochondrial pathway and arrested the cell cycle by regulation of cell cycle-related proteins in MHCC97H cells without an effect on normal cells. The cancer-specific selectivity shown in their study suggests that the plant extract could be a promising novel treatment for human cancer.

1. Li ZF, Wang ZD, Ji YY, Zhang S, Huang C, Li J, Xia XM. Induction of apoptosis and cell cycle arrest in human HCC MHCC97H cells with Chrysanthemum indicum extract. World Journal of Gastroenterology, 2009; 15 (36): 4538 DOI: 10.3748/wjg.15.4538

ScienceDaily (Sep. 26, 2009) — Huachansu, a Chinese medicine that comes from the dried venom secreted by the skin glands of toads, has tolerable toxicity levels, even at doses eight times those normally administered, and may slow disease progression in some cancer patients, say researchers from The University of Texas M. D. Anderson Cancer Center.

The results from the Phase I clinical study, a collaborative research project between M. D. Anderson and Fudan University Cancer Hospital in Shanghai, are reported in the online Early View feature of the journal Cancer. The study marks the first time a formal clinical trial has examined the relationship between huachansu dose and toxicity, although the drug is common in China and approved by the Chinese Food and Drug Administration.

Huachansu is widely used to treat patients with liver, lung, colon and pancreatic cancer at oncology clinics in China. Chinese clinical trials conducted since the 1970s have demonstrated the anti-cancer properties of huachansu, citing total response rates of 10 percent and 16 percent observed in patients with advanced hepatocellular carcinoma and lung cancer, respectively1,2.

“Studying traditional Chinese medicine such as huachansu is new to American research institutions, which have been skeptical and slow to adopt these complementary treatments. However, it is important to understand its potential role in treating cancer,” says Lorenzo Cohen, Ph.D., one of the paper’s authors and director of the Integrative Medicine Program at M. D. Anderson. “We wanted to apply a Western medicine-based approach to explore the role of the toad venom compound in cancer patients and test if it is possible to deliver a more potent dose without raising toxicities or side effects.”

The clinical trial was conducted at the Fudan University Cancer Hospital while M. D. Anderson provided training and ongoing consultation. The institutions collaboratively designed the trial that was approved by both institutional review boards. M. D. Anderson and Fudan University Cancer Hospital signed a sister institution agreement in 2003, creating a framework for research, educational and clinical collaboration.

The typical dose of huachansu used in China is approximately 15 milliliters of drug per meter squared of body mass (mL/m2). In the study, 15 patients with stage III or IV hepatocellular (liver) carcinoma, nonsmall cell lung cancer or pancreatic cancer received one of five dose levels ranging from 10 mL/ m2 up to 90 mL/m2 from January 2005 through July 2006. The treatment was repeated daily for 14 days followed by seven days off (one cycle). After two cycles, most patients received other treatments. Quality control methods were put in place to ensure huachansu of a uniform and consistent lot.

While the dose was up to eight times higher than conventional doses used in China, researchers observed only low toxicities or side effects. Eleven (73 percent) patients had no toxicities greater than the lowest grade measured. Importantly, no significant cardiac toxicity was observed and no significant changes in cancer-related symptoms occurred. Of the 15 patients who completed the treatment, six hepatocellular carcinoma patients (40 percent) had stable disease for a median of six months. One patient had a 20 percent reduction in tumor mass that lasted for more than 11 months.

“Even though we saw no complete or partial response (reduction of disease by 30 percent or more) it is encouraging that the cancer did not progress in a large set of the hepatocellular carcinoma patients,” says Zhiqiang Meng, principal investigator on the trial and an associate professor and deputy chair of the Department of Integrative Oncology at Fudan University Cancer Hospital, “Previous observations from studies conducted in China have shown that huachansu can inhibit tumor cell growth and improve immunologic function3. These findings, coupled with that knowledge, demonstrate the need for further clinical trials of this promising agent.”

A Phase II clinical trial comparing the effects of huachansu combined with gemcitabine (Gemzar®) to gemcitabine and placebo for patients with advanced pancreatic cancer is under way at the Fudan University Cancer Hospital in collaboration with M. D. Anderson.

Both trials are part of the International Center of Traditional Chinese Medicine for Cancer funded by the National Cancer Institute. Anhui Jinchan Biochemistry Company, Ltd. provided the drug for this trial.

In addition to Cohen, other M. D. Anderson faculty contributing to this study include Peiying Yang, MD, the Integrative Medicine Program in the Department of Medical Oncology; David Z. Chang, MD, Department of Gastrointestinal Medical Oncology; Zongxing Liao, MD, Department of Radiation Oncology; and Razelle Kurzrock, MD, Department of Investigational Cancer Therapeutics. In addition to Meng, other Fudan University researchers contributing to this study include Yehua Shen, MD; Wenying Bei, MD; Ying Zhang, MD; Yongqian Ge, MD; and Luming Liu, MD, PhD. Formerly of M. D. Anderson, Robert A. Newman, MD, now of New Chapter Inc. and Bob Thornton, MD, now of Merck & Co, Inc. also contributed to this study.

—Heather S. Oliff, PhD

Maitake (Grifola frondosa) is an edible mushroom used in East Asian traditional medicine. Laboratory and animal studies suggest that polysaccharides extracted from maitake have immune modulating and antitumor properties. Many cancer patients use maitake extract to boost their immune function. However, well-designed trials evaluating clinical benefits in people with cancer have not been conducted. Before such trials can be conducted, the optimal dose of maitake must be determined. The purpose of this trial was to evaluate the safety, tolerability, and immunological effects of a range of doses of maitake extract on women with breast cancer.   

This phase I/II dose-escalating trial was conducted at Memorial Sloan-Kettering Cancer Center in New York City. The trial included 34 postmenopausal women who had completed treatment for breast cancer and were cancer-free. The women were enrolled sequentially into 1 of 5 dose cohorts and took 0.2, 1.0, 3.0, 6.0, or 10 mg/kg per day of oral maitake extract (taken in 2 divided doses) for 21 days. The extract was prepared by extracting fruit bodies of maitake mushrooms with hot water and alcohol. The extract was provided by Yuikiguni Maitake Corporation through the Tradeworks Group (Brattleboro, Vermont). The extract was formulated in liquid form and packaged by Gaia Herbs (Brevard, North Carolina).

The women completed an interview and physical examination at the beginning and end of the study. They were instructed to report any adverse side effects or new symptoms immediately. Blood samples were collected before the women started taking the maitake extract and again at 7, 14, and 21 days after starting the extract. The blood samples were analyzed for cell type, cell markers, and intracellular production of cytokines, including several interleukins (IL), interferon-gamma (INF-γ), and tumor necrosis factor alpha (TNF-α).

The 34 women ranged in age from 38 to 77 years, with a median age of 55 years. Two women withdrew from the study because of adverse side effects. One woman in the 1.0 mg/kg cohort experienced nausea and joint swelling, and 1 woman in the 10 mg/kg cohort had a mild allergic reaction. No serious side effects were reported by any of the women.

There was a statistically significant relationship (P < 0.005) between the dose of maitake and the immunological response for 25 of the 146 measured parameters, which represented an overall statistically significant association between maitake and immunological function (P < 0.0005). Increasing the dose of maitake increased some immunologic parameters and depressed others. The largest increases were seen in granulocyte (a type of white blood cell) response; IL-10 production from certain types of cells (CD14+ and CD3+); IL-2 production from certain types of cells (CD56+ CD3+); and TNF-α production from CD3+ cells. All of these parameters had the largest increase at an intermediate dose of maitake (5-7 mg/kg per day, based on dose-response curves). For many of the immunologic parameters, intermediate doses had greater effects than higher or lower doses.

In summarizing the results of this trial, the authors state that maitake extract is associated with significant changes in certain immunologic parameters in the blood, that maitake extract has a stimulatory effect on some parameters and a suppressive effect on other parameters, and that the “optimal” dose of maitake extract varies for different immunologic parameters. The finding that maitake extract also increases some immune-suppressing cytokines in the blood contradicts the public perception that maitake boosts the immune system. In this study, maitake extract was well-tolerated, and no dose-limiting toxicity was observed. It is unclear if the tested extract is a marketed, and therefore available, extract.

The clinical significance of these immunological changes is unknown, particularly in the setting of cancer prevention and cancer treatment. Since maitake’s effects on immune function are complex, it should be viewed as an immune modulator rather than an immune enhancer.

Reference:

Deng G, Lin H, Seidman A, et al. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin Oncol. 2009 Sep;135(9): 1215-1221.

Hardy ML. Dietary supplement use in cancer care: help or harm. Hematol Oncol Clin N Am. 2008;22: 581-617.

Studies consistently show that most cancer patients use dietary supplements (DS) in all phases of treatment, most often without revealing use, or revealing it only partially, to oncologists. Most oncologists recommend complete avoidance of DS, reducing patients’ willingness to disclose use and thereby potentially increasing risks. Overall, physicians and patients do not share the same perceptions of possible benefits from complementary and alternative medicine (CAM) or agree on what evidence to use for CAM therapy.

Some risks cited by oncologists for CAM use are not fully supported by research. These include fears that patients using CAM may refuse or delay conventional treatment or that CAM products may be contaminated or adulterated, and risk of liver toxicity from DS. The author states that these risks are relatively small and would be best guarded against by physician-patient communication. In one study, only 8% of advanced cancer patients were receiving alternative care alone. According to the author, contaminated or adulterated DS should be substantially reduced under new rules from the Food and Drug Administration. Not all evidence of liver toxicity for herbs is equally compelling; in particular, reports involving black cohosh (Actaea racemosa syn. Cimicifuga racemosa) were insufficiently persuasive for the National Institutes of Health to halt or modify clinical trials.

Herb-drug interactions, another risk cited by oncologists, have been the subject of several reviews, but only two studies. In one, of 76 chemotherapy patients, three were using botanical DS that could interfere with the chemotherapeutic agent: St. John’s wort (SJW; Hypericum perforatum) and garlic (Allium sativum). In another, of 318 chemotherapy patients also taking herbs, 11% took DS in higher-than-recommended doses. Potential interactions were inferred for 12%, mostly with echinacea (Echinacea spp.) on the presumption that it might adversely affect immune stimulation. However, neither study confirmed any interactions. In screening tests, herbal preparations have shown the ability to up- or down-regulate activity of P450 isoenzymes, but relatively few clinical trials have verified this. One review assessed in vitro, in vivo, and human data for common herbs concluding that, in chemotherapy, interactions with black cohosh, milk thistle (Silybum marianum), saw palmetto (Serenoa repens), cranberry (Vaccinium macrocarpon), and bilberry (Vaccinium myrtillus) were not expected. Mostly preclinical research suggests that for garlic, ginkgo (Ginkgo biloba), soy (Glycine max), Asian ginseng (Panax ginseng), valerian (Valeriana officinalis), and kava (Piper methysticum), precautions should be taken. Human studies with SJW and imatinib found reduced levels and increased clearance of the drug; similar results were found for SJW and irinotecan. Induction of CYP450 enzymes is thought to be caused by hyperforin, one constituent of SJW. In no pharmacokinetic study cited was composition of the SJW extract described or independently confirmed by investigators.

Reduced blood coagulation, perhaps due to antiplatelet action or interference with warfarin, is also cited as a risk for cancer patients using DS. Evidence for either effect is mixed with mostly poor quality case reports unsupported by in vivo research.

Some herbs’ phytohormonal effects cause concern for oncologists with regards to hormone-sensitive cancers, particularly breast, ovarian, endometrial, or prostate. Research has focused on estrogenic activity in menopause. Both soy and red clover (Trifolium pratense) extracts are phytoestrogenic, with uncertain significance for estrogen receptor-positive breast cancer patients. Black cohosh, however, does not appear to be estrogenic. Activity on serotonergic neutrons in the hypothalamus may account for its effects on symptoms of menopause.

While eating antioxidant-rich foods is associated with reduced risk of many cancers, using antioxidant DS to prevent cancer is not supported by large randomized trials and has at times been found to increase risk. However, a large amount of preclinical data and some human trials support use of some antioxidants, e.g., high-dose vitamin C for possible tumor response; and vitamins C, E, and coenzyme Q10 to reduce chemotherapy-related toxicity. Some evidence for harm exists for vitamin E use in head and neck cancers.

                                                                * * *

While most perceived risks remain theoretical or even unlikely, benefits are found for cancer patients from many CAM products in overall quality of life and reduced side effects of conventional treatment. The author omits discussion of lectin compounds from mistletoe (Viscum album), and a polysaccharide extract from shiitake mushroom (Lentinus edodes), because both are delivered parenterally or intravenously, and therefore are not DS by US standards; and omits whole-herb cannabis (Cannabis sativa) extracts and isolated compounds because of “legal ambiguity and challenges with standardization.”

Among immunomodulators, mushrooms and mushroom-derived polysaccharides improved quality of life, modified tumor response, and boosted immune response in several cancer models and some clinical trials, mostly in patients with solid tumors. A proprietary extract of turkey tail mushroom (Trametes versicolor syn. Coriolus versicolor), PSK® (JHS Natural Products; Eugene, Oregon), showed those benefits and lower relative risk of regional metastases, in trials of over 1200 subjects with colorectal cancer and over 8000 with gastric cancer. Another turkey tail extract, together with danshen (Salvia miltiorrhiza), improved immunological parameters in nasopharyngeal cancer patients having radiation therapy and in breast cancer patients. A polysaccharide extract of a proprietary hybrid mushroom identified as Basidiomycotina (probably Agaricus blazei), has shown beneficial immune effects in clinical trials, and a highly significant statistical increase in survival in some advanced liver cancer patients. An A. blazei extract given to gynecological cancer patients increased natural killer cell activity and decreased chemotherapy side effects from carboplatin, etoposide, or taxol. Other promising immunomodulators include a proprietary fermented wheat (Triticum spp.) germ extract standardized to methoxy-substituted benzoquinones (Avé® or Avemar®; American BioSciences; Blauvelt, New York), and probiotics. Unexpected and still unexplained deaths in a recent trial of probiotics in patients with severe pancreatitis mandate caution.

Stomatitis or mucositis, a common side effect of cancer therapy, reduces quality of life and caloric intake. Simple natural interventions, such as ice (plain or flavored), honey, and topical vitamin E oil, reduce stomatitis. There is strong evidence, in several cancers and with a variety of chemotherapeutic agents, for glutamine as an oral rinse that is then swallowed; however, results with 5-fluorouracil (5-FU) chemotherapy were generally negative. Zinc supplementation, a proprietary homeopathic remedy (Traumeel®; Heel, Inc.; Albuquerque, New Mexico) containing arnica (Arnica montana), and proteolytic enzymes have all shown benefit. Aloe (Aloe vera) and chamomile (Matricaria recutita) rinses have had mixed results. Chamomile fared better in uncontrolled cases with heterogenous chemotherapy and radiation than in a controlled study with 5-FU. Stomatitis is often associated with disruption of gut mucosa leading to diarrhea or leaky gut syndrome. Glutamine benefited 5-FU-induced intestinal toxicity and diarrhea associated with irinotecan in some studies, but not diarrhea from doxifluridine or neo-adjuvant chemotherapy or radiation in others. Even when no benefit was found, there was no interference with chemotherapy. Probiotics decreased diarrhea when given concurrently with 5-FU chemotherapy or radiation; again, caution is currently warranted. Both glutamine and vitamin E have shown promise in alleviating chemotherapy-induced neuropathies, caused especially by platinum-based drugs and taxanes. Ginger (Zingiber officinale), in doses as low as 1 g/d powdered root, reduces chemotherapy-induced nausea, with no serious adverse effects, and fewer side effects than metoclopramide.

Radiation therapy damages skin contributing to morbidity. So far, few herbal agents have shown benefit. Aloe is often used for radiation-induced burns, but trials have not confirmed a strong benefit. It has delayed onset of damage briefly. A proprietary chamomile cream, compared to almond (Prunus dulcis) oil, delayed onset of dermatitis and reduced damage, though the differences were not statistically significant. Those using a homeopathic calendula (Calendula officinalis) cream compared with trolamine during radiation had significantly less dermatitis and were more satisfied with the calendula cream despite its being more difficult to use.

Reviews and meta-analyses confirm the usefulness of omega-3 fatty acids in preventing cancer-related cachexia, but relatively high doses are required for efficacy: 7.5 g/d fish oil or eicosapentaenoic acid (EPA). Combining fish oil with celecoxib gave significantly more improvement in appetite, fatigue, body weight, and muscle strength than fish oil alone in a small group of patients with advanced lung cancer.

Edema after conventional cancer treatments can be a serious issue and difficult to treat. One randomized trial with selenium selenite reduced upper extremity edema and improved function of breast cancer patients, while an uncontrolled trial showed its benefit for head and neck radiotherapy. Several small studies with flavonoid-rich preparations have shown benefit, including one using a proprietary ginkgo formula.

DS studied for cancer-related fatigue have generally been ineffective, but supplementation with up to 3000 mg/d carnitine decreased fatigue and improved quality of life in carnitine-deficient patients during chemotherapy.

Black cohosh – as discussed earlier, effective against symptoms of menopause but not estrogenic – has been suggested for vasomotor symptoms in cancer therapy, especially in younger women. Not all trials have shown benefits in women with breast cancer, but some have, without serious adverse effects. And, far from increasing breast cancer risk, two studies found a possible protective effect of black cohosh extract (BCE). In a case-controlled study of 949 menopausal breast cancer patients and 1524 menopausal controls, women who took BCE had 50% less risk of developing breast cancer. In a retrospective cohort study comparing 1102 breast cancer survivors who took BCE with a small group who did not, those who used BCE had longer disease-free intervals.

While DS are inappropriate as primary cancer treatments, some show promise in pre-malignant lesions, early cancers usually treated with watchful waiting, and specific treatment-resistant cancers. Subjects with oral leukoplakia received 3 g tea (Camellia sinensis) or placebo. After six months, the treatment group had smaller lesions and fewer micronucleated exfoliated cells. High-grade intraepithelial neoplasia of the prostate (HG-PIN) has responded to oral administration of a green tea extract. Pomegranate (Punica granatum) juice (POM Wonderful®; POM Wonderful, Inc.; Los Angeles, California), given to men with rising prostate-specific antigen (PSA) after surgery or radiation, increased mean PSA-doubling time from 15 to 54 months. Another DS with soy, lycopene, silymarin, and antioxidants increased PSA-doubling time from 445 to 1,150 days. Some tumor response was seen in a trial of 10 mg/d lycopene (Lycored®; LycoRed Natural Product Industries; Beer Sheva, Israel) supplementation, for three months, in men with hormone-resistant or refractory prostate cancer (HRPC). Most were able to reduce the amount of analgesics used. Lycopene with orchiectomy improved outcomes of men with metastatic HRPC. However, given to HRPC patients as tomato (Lycopersicon esculentum) paste or juice, it showed no effect.

Oncologists are urged to become familiar with literature on DS in cancer and to accept that the majority of their patients will use DS, with or without their knowledge or approval. Being able to discuss well-characterized, well-tested products can help minimize risks. Finally, it is critical that additional research examine benefits and risks of DS use in cancer.

 —Mariann Garner-Wizard

By Stephen Daniells, 31-Jul-2009

Using Chinese herbs either alone or in conjunction with chemotherapy may help protect a breast cancer patient’s bone marrow and immune system, as well as improving the woman’s overall quality of life.

Sixty per cent of women undergoing chemotherapy for breast cancer experience a range of significant short term side effects. These include nausea, vomiting and fatigue, as well as inflammation of the gut lining, decreased numbers of red and white blood cells and decreased numbers of blood platelets.

Chinese medicinal herbs include mixtures of herbal compounds or extracts from herbs, and they are prescribed to counteract the side effects of chemotherapy. This Cochrane Systematic Review set out to see if there is conventional evidence indicating that these medicines are safe and whether there is evidence that the medicines are effective.

The researchers identified seven randomised studies involving 542 patients with breast cancer. By analysing these data, the researchers concluded that there was no evidence that the Chinese medicinal herbal treatment caused harm, and some evidence that it might reduce side effects.

“Further trials are needed before the effects of traditional Chinese medicines for people with breast cancer can be evaluated with any real confidence,” says Assistant Professor Jing Li, who works at the Chinese Cochrane Centre in Chengdu, China.

Ginseng, one of the most widely used herbs in traditional Chinese medicine, may improve survival and quality of life after a diagnosis of breast cancer, according to a recent study by Vanderbilt-Ingram Cancer Center researchers.

Ginseng is a slow-growing perennial herb whose roots have been used in traditional Chinese medicine for more than 2,000 years. The two main classes of ginseng — red and white — have different biological effects, according to traditional Chinese medicine theory. White, or unprocessed, ginseng is used over long periods to promote general health, vitality and longevity. Red, or processed, ginseng provides a much stronger effect and is used for short periods to aid in disease recovery.

Both varieties of ginseng contain more than 30 chemicals, called ginsenosides, which have anti-tumor effects in cell culture and animal studies, suggesting that the herbs may provide specific benefits to cancer patients. In fact, ginseng use has been increasing among cancer patients in recent years, particularly in women diagnosed with breast cancer.

However, despite the encouraging laboratory findings, scientific analysis of ginseng’s health benefits in patient populations has been lacking. “There is a lot of skepticism about herbal medicine,” said Shu. “That is why we are taking the observational approach at this time to see whether there is any efficacy. If so, we can go to the next phase … and eventually go to clinical trials.”

Shu and colleagues assessed the effects of ginseng use in breast cancer survivors as part of a large epidemiological study, the Shanghai Breast Cancer Study, which has followed 1,455 breast cancer patients in Shanghai since 1996. For the current study, Shu and colleagues evaluated breast cancer patients for ginseng use both before and after their diagnosis of breast cancer. All patients who used ginseng had received at least one type of conventional cancer therapy (e.g., surgery, chemotherapy and/or radiotherapy).

Information on ginseng use prior to cancer diagnosis, which was available for every subject, was used to determine whether prior ginseng use predicted survival. At follow up — about three to four years after diagnosis — the researchers asked about ginseng use since diagnosis. That information, which was available only for survivors, was used to look at quality of life measurements — i.e., physical, psychological, social and material well-being.

Before diagnosis, about a quarter of patients (27.4 percent) reported using ginseng regularly. After diagnosis, that percentage jumped to 62.8 percent, the researchers found. They also found significant improvements in both survival and quality of life measures in patients who used ginseng. “When patients used ginseng prior to diagnosis, they tended to have higher survival,” Shu explained. “Ginseng use after cancer diagnosis was related to improved quality of life.”

The findings suggest that ginseng may provide tangible benefits to breast cancer survivors, but there are limitations to the study. The varieties and the methods of ginseng use and the use of other complementary and alternative therapies could not be fully accounted for in the analysis. Also, the quality of life measures exclusively relied on patient self-reporting.

Although side effects of ginseng use were not recorded in this study, Shu warned that the seemingly innocuous root can create problems when improperly used and should be taken with caution. “It’s not a ‘drug’ in terms of being managed by the FDA, but it was used as a drug in traditional Chinese medicine,” she said. “Any drug may have some side effects and may interact with other drugs. So, discuss with your primary care doctor before you decide to take ginseng roots or products.”

Shu hopes to confirm and expand the current findings through continued collection of data in this patient population, from another ongoing study of 4,000 breast cancer patients, and eventually, in randomized clinical trials. Scientific study of complementary and alternative medicines is tricky though, said Shu. “Chinese traditional medicine is very individualized. It gives you different drugs based on your symptoms and your overall health. There is much to be learnt.”

 The large epidemiological study, led by Xiao-Ou Shu, M.D., Ph.D., was published online recently in the American Journal of Epidemiology.

Other authors on the paper were Yong Cui, M.D., Hui Cai, M.D., Ph.D., Meng-Hua Tao, M.D., and Wei Zheng, M.D., Ph.D., from Vanderbilt and Yu-Tang Gao, M.D., from the Shanghai Cancer Institute. The research was supported by grants from the National Cancer Institute.