K. Simon Yeung

Randomized, Controlled Trial of Acupuncture for the Treatment of Hot Flashes in Breast Cancer Patients

PURPOSE To determine the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer. PATIENTS AND METHODS Seventy-two women with breast cancer experiencing three or more hot flashes per day were randomly assigned to receive either true or sham acupuncture. Interventions were given twice weekly for 4 consecutive weeks. Hot flash frequency was evaluated at baseline, at 6 weeks, and at 6 months after initiation of treatment. Patients initially randomly assigned to the sham group were crossed over to true acupuncture starting at week 7. RESULTS The mean number of hot flashes per day was reduced from 8.7 (standard deviation [SD], 3.9) to 6.2 (SD, 4.2) in the true acupuncture group and from 10.0 (SD, 6.1) to 7.6 (SD, 5.7) in the sham group. True acupuncture was associated with 0.8 fewer hot flashes per day than sham at 6 weeks, but the difference did not reach statistical significance (95% CI, -0.7 to 2.4; P = .3). When participants in the sham acupuncture group were crossed over to true acupuncture, a further reduction in the frequency of hot flashes was seen. This reduction in hot flash frequency persisted for up to 6 months after the completion of treatment. CONCLUSION Hot flash frequency in breast cancer patients was reduced following acupuncture. However, when compared with sham acupuncture, the reduction by the acupuncture regimen as provided in the current study did not reach statistical significance. We cannot exclude the possibility that a longer and more intense acupuncture intervention could produce a larger reduction of these symptoms.

Acupuncture for Pain and Dysfunction After Neck Dissection: Results of a Randomized Controlled Trial

PURPOSE To determine whether acupuncture reduces pain and dysfunction in patients with cancer with a history of neck dissection. The secondary objective is to determine whether acupuncture relieves dry mouth in this population. PATIENTS AND METHODS Patients at a tertiary cancer center with chronic pain or dysfunction attributed to neck dissection were randomly assigned to weekly acupuncture versus usual care (eg, physical therapy, analgesia, and/or anti-inflammatory drugs, per patient preference or physician recommendation) for 4 weeks. The Constant-Murley score, a composite measure of pain, function, and activities of daily living, was the primary outcome measure. Xerostomia, a secondary end point, was assessed using the Xerostomia Inventory. RESULTS Fifty-eight evaluable patients were accrued and randomly assigned from 2004 to 2007 (28 and 30 patients on acupuncture and control arms, respectively). Constant-Murley scores improved more in the acupuncture group (adjusted difference between groups = 11.2; 95% CI, 3.0 to 19.3; P = .008). Acupuncture produced greater improvement in reported xerostomia (adjusted difference in Xerostomia Inventory = -5.8; 95% CI, -0.9 to -10.7; P = .02). CONCLUSION Significant reductions in pain, dysfunction, and xerostomia were observed in patients receiving acupuncture versus usual care. Although further study is needed, these data support the potential role of acupuncture in addressing post-neck dissection pain and dysfunction, as well as xerostomia.

Evaluation of widely consumed botanicals as immunological adjuvants.

BACKGROUND Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with seven botanicals purported to have immune stimulant effects. METHODS Groups of 5-10 mice were immunized with globo H-KLH or GD3-KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. three times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus versicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co. Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast beta-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semisynthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH. RESULTS Consistent significant adjuvant activity was observed after s.c. vaccination with the Coriolus extracts (especially PSK), a 95% ethanol extract of Astragalus and yeast beta-glucan, and (to a lesser extent) Maitake. Antibodies against KLH in all cases and against globo H in most cases were induced by these botanicals. Little or no adjuvant activity was demonstrated with H-48 or Echinacea extracts or the Astragalus water extract. Experiments with GD3-KLH as immunogen confirmed the adjuvant activity of the Coriolus, yeast beta-glucan and Astragalus extracts. While extraction with ethanol concentrated the active ingredients in Astragalus, it had no impact on Coriolus where the 90% ethanol precipitate and solute were equally active. CONCLUSIONS Some, but not all, botanicals purported to be immune stimulants had adjuvant activity in our model. PSK and Astragalus were surprisingly active and are being further fractionated to identify the most active adjuvant components.

Acupuncture in the Treatment of Upper-Limb Lymphedema: Results of a Pilot Study

Current treatments for lymphedema after breast cancer treatment are expensive and require ongoing intervention. Clinical experience and our preliminary published results suggest that acupuncture is safe and potentially useful. This study evaluates the safety and potential efficacy of acupuncture on upper‐limb circumference in women with lymphedema.

Herbs and other botanicals in cancer patient care.

Opinion statementNon-prescription herbal remedies are commonly used by cancer patients in efforts to control their disease or to manage symptoms associated with cancer and cancer treatments. We address the issues surrounding the use of herbs, herbal compounds, and other botanical agents in the oncology context. Botanicals are biologically active agents that can be useful under appropriate circumstances, but they may be counterproductive when used by patients on chemotherapy or on other prescription medications. Herbs and other botanical agents, despite common public belief, are not benign. They should be understood as unrefined pharmaceuticals, with the capacity to produce physiologic change for better or worse. Indeed, many prescription drugs, chemotherapeutic agents among them, were derived from plants and other natural agents, and the search for additional constituents of plants, animals, and minerals for use as pharmaceutical agents remains an active effort on many fronts. Cautions, appropriate application, and potential utility of botanical agents are discussed below, and sources of reliable information are provided.

Evidence-Based Botanical Research: Applications and Challenges

Use of herbal supplements is on the rise around the world, but limited data exist on the safety and efficacy of botanical products. Efforts to subject botanicals to rigorous scientific research began recently. There are many problems associated with botanicals research, however. These include procuring the study agents, selecting appropriate study method and clinical trial design, navigating through regulatory obstacles, and obtaining funding. Evidence-based botanical research can help to validate traditional uses and to facilitate new drug development. Concerted efforts of governmental agencies and industry are essential to ensure continuance of high-quality botanicals research.

The known immunologically active components of Astragalus account for only a small proportion of the immunological adjuvant activity when combined with conjugate vaccines.

The 95 % ethanol extract of Astragalus has been demonstrated to have potent activity as an immunological adjuvant when administered with vaccines of various types. We endeavor here to identify the components of this extract that are responsible for this adjuvant activity. Mice were immunized with KLH conjugated to cancer carbohydrate antigens globo H and GD3 and cancer peptide antigen MUC1 combined with different Astragalus fractions or with commercially available Astragalus saponins and flavonoids. The antibody responses against cancer antigens and KLH were quantitated in ELISA assays, and toxicity was calculated by weight loss. Astragalosides II and IV were the most active components, but the toxicity of these two differed dramatically. Astragaloside II was the most toxic Astragalus component with 5-10 % weight loss at a dose of 500 µg while astragaloside IV showed no weight loss at all at this dose, suggesting that astragaloside IV might be utilized as an immunological adjuvant in future studies. Several flavonoids also had significant adjuvant activity. However, when the activities of these known immunologically active components of Astragalus (and of endotoxin) are calculated based on the extent of their presence in the 95 % ethanol extract, they provide only a small proportion of the immunological activity. This raises the possibility that additional uniquely active components of Astragalus may contribute to adjuvant activity, or that the adjuvant activity of Astragalus is greater than the activity of the sum of its parts.

An Evidence-based Review of Astragalus membranaceus (Astragalus) for Cancer Patients

Astragalus membranaceus (astragalus), originally described in the Shennong’s Classic of Materia Medica two thousand years ago, is used as a Qi-tonifying herb in traditional Chinese medicine. It is an important ingredient in many herbal formulas used to treat a variety of symptoms and ailments including fatigue and rectal prolapse. The root of astragalus is rich in saponins and polysaccharides. Modern research suggests antioxidant, immunomodulatory, and cytostatic properties. Animal and anecdotal human data show that astragalus reduces immunosuppression, a side effect of chemotherapy and it may also enhance the effects of such treatments. Whereas oral and parenteral preparations have been developed in Asia, products containing astragalus are consumed as dietary supplements in the West. Several formulas containing astragalus have been studied in cancer patients. Data indicate that they are safe to use in conjunction with chemotherapy and reduce treatment associated adverse effects. Based on existing evidence, there is also substantial interest in developing astragalus-based preparations for certain cancers. Although all products studied to date contain astragalus as the main ingredient, the variation across formulas makes it difficult to draw definitive conclusions. Future studies should address this issue. Astragalus is generally considered safe for traditional use, but the potential for herb-drug interactions exists because botanicals contain biologically active compounds. This chapter presents information about the use of astragalus in traditional medicine and summarizes existing scientific evidence of its benefits and limitations as an adjuvant cancer treatment.

Herbal medicine for depression and anxiety: A systematic review with assessment of potential psycho-oncologic relevance

Anxiety and depression are prevalent among cancer patients, with significant negative impact. Many patients prefer herbs for symptom relief to conventional medications which have limited efficacy/side effects. We identified single‐herb medicines that may warrant further study in cancer patients. Our search included PubMed, Allied and Complementary Medicine, Embase, and Cochrane databases, selecting only single‐herb randomized controlled trials between 1996 and 2016 in any population for data extraction, excluding herbs with known potential for interactions with cancer treatments. One hundred articles involving 38 botanicals met our criteria. Among herbs most studied (≥6 randomized controlled trials each), lavender, passionflower, and saffron produced benefits comparable to standard anxiolytics and antidepressants. Black cohosh, chamomile, and chasteberry are also promising. Anxiety or depressive symptoms were measured in all studies, but not always as primary endpoints. Overall, 45% of studies reported positive findings with fewer adverse effects compared with conventional medications. Based on available data, black cohosh, chamomile, chasteberry, lavender, passionflower, and saffron appear useful in mitigating anxiety or depression with favorable risk–benefit profiles compared to standard treatments. These may benefit cancer patients by minimizing medication load and accompanying side effects. However, well‐designed larger clinical trials are needed before these herbs can be recommended and to further assess their psycho‐oncologic relevance.

Correction: Integrative medicine: complementary therapies and supplements

Cassileth, B. et al. Integrative medicine: complementary therapies and supplements. Nat. Rev. Urol. 6, 228–233 (2009). In the April 2009 issue of Nature Reviews Urology, the following Acknowledgment should have been included: “This work was supported in part by Award Number P50AT002779 from the National Center for Complementary & Alternative Medicine.