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The CAM in UME Project http://www.caminume.ca This material is made available through The CAM in UME Digital Resource Repository and is owned and copyrighted by the credited author(s). Materials are provided for educational purposes only. All copied materials must contain clear and proper citation. Complementary Therapies and Cancer Doreen Oneschuk, MD University of Alberta 18 May 2010 URL: http://www.caminume.ca/drr/resources/00024.ppt 59 slides Delivered to 2nd year medical students during Oncology Block The CAM in UME Project does not warrant or assume any legal liability or responsibility for the accuracy, completeness, or usefulness of any information presented herein. Complementary Therapies and Cancer Dr. D. Oneschuk May 18, 2010 Objectives Become familiar with the use of several natural health products for cancer prevention and treatment Be able to discuss the potential for natural health products to interact with other medications including CTX and RTX Be able to describe the use of other complementary therapies such as acupuncture, massage, in cancer and supportive care management Commonly Used Therapies and Their Evidence Base Natural Health Products- A Taste Prevention Green Tea Soy Products Generalized Cancer Treatment Mistletoe Reishi Mushrooms Specific to Cancer Pain and Other Symptoms Acupuncture Mind-Body/Relaxation Therapies (Hypnosis, Guided Imagery, Meditation) Massage and Reflexology Energy Healing Techniques-Reiki and Therapeutic Touch Green Tea Made by steaming fresh cut leaves of an evergreen bush-Camellia sinensis Fermentation process does not occur-no oxidation of active constituents including polyphenols Including Flavanols-Epigallocatechin gallate (EPCG) appears to be most important flavanol Mechanism of Action Inhibit inflammatory cytokines related to carcinogensis Inhibition of angiogenesis Inhibition of urokinase involved in metastases Antioxidant reducing DNA damage Evidence Based Efficacy Cochrane Collaboration Systematic Review (2009) 51 studies reviewed, 1.6 million participants Mainly observational studies with medium to high methodological quality Evidence based Efficacy Conflicting evidence for esophageal, gastric, colon, rectum, and pancreas Studies suggested decreased risk of prostate cancer in men consuming higher quantities of green tea, and green tea extracts Limited to moderate evidence for lung, pancreas, and colorectal cancer Potential for increased risk of bladder cancer Required Amount and Safety No severe adverse effects reported with medicinal use High doses (i.e. 5-6 liters per day)- nausea, vomiting, abdominal bloating, diarrhea CNS stimulation with too much caffeine Safety during pregnancy and lactation-not established Drug Interactions with Green Tea Mainly effect of Caffeine- ↑ BP-watch with those on B-blockers Counteract effects of benzodiazepines In large amounts- Vitamin K effectsantagonize effects of anticoagulants Tannin content may reduce bioavailability of iron Bottom Line Insufficient and conflicting evidence to provide firm recommendations for cancer prevention Appears to be safe with moderate, regular, and habitual use Desirable intake 3-5 cups per day, minimum 250 mg/day catechins Soy Products- Mechanism of Action Active constituents: phytoestrogens, lignans, isoflavones, notable genistein Genistein-shown to inhibit carcinogenesis in animal models Modulates genes that are related to cell cycle control and apoptosis Antioxidant and anti-angiogenesis properties Evidence based Efficacy Decreases risk of breast and prostate cancer Inhibits growth of leukemia, lymphoma, lung, head and neck cancers Potential for increased risk of bladder and prostate cancer Safety Generally considered safe Potential side effects: constipation, diarrhea, bloating, nausea, allergic skin rash Precautions with hormone sensitive malignancies (ovary, uterine), hypothyroidism, renal calculi, bladder cancer, endometriosis Safety High dose not recommended in pregnancy, and breast feeding Soy may increase or decrease effects of estrogen Taken with warfarin, may lower the INR, and decrease iron absorption Safety The Big Controversy? Use in Breast Cancer?! The Issue: Isoflavones may act as mixed estrogen receptor promoters (agonists), may function like SERMstherefore, may stimulate growth of estrogen-sensitive breast tumors (in vitro and rodent data) Safety There is little clinical and epidemiological data to suggest the isoflavones will increase breast cancer risk in healthy women or worsen the prognosis of breast cancer patients American Cancer Society, 2006, breast cancer pts can safely consume up to 3 servings of traditional soyfoods per day, but avoid more concentrated sources of isoflavones such as powders and liquids Bottom Line Soy appears to have protective effects for a variety of cancers, but evidence is not clear for any specific dose or cancer type May be associated with a small reduction in breast cancer risk, if commenced in adolescence Mistletoe Most common complementary anticancer therapy prescribed in Germany Plant that lives symbiotically with different trees species such as pine, apple, and oak tree Various types of mistletoe treat different types of cancer Mechanism of Action Stimulates the immune system: increases cytokine production, WBCs, secretion of TNF May have cytotoxic effect on tumor cells Given as a subcutaneous injection into the abdomen wall or into the tumor Toxic when taken orally- do not nip on the bough during Christmas! Evidence Based Efficacy Systematic Review (2009)- 18 clinical trials involving >6,800 participants Internal quality of studies were low Inconsistent findings regarding life expectancy, dosing, and treatment duration However, quality of life (QoL) is improved Evidence Based Efficacy 14/16 trials showed improvement in QoL, psychological measures, performance index, symptom scales, or the reduction of adverse events of chemotherapy-2 studies were of higher methodological quality Safety & Drug Interactions Systematic Review: one serious adverse event Potential multiple adverse effects: skin related (local reactions at injection sites), pain, fatigue, fever, sweating, dehydration, confusion, diarrhea, vomiting, blood pressure changes and others……….. Can enhance effects of antiHTN drugs, cardiac suppressants, and CNS depressants Bottom Line Supportive ‘mistletoe therapy’ seems safe and beneficial for QoL in adult patients with solid tumors However, evidence from RCTs to improve survival, ability to fight cancer, or withstand anticancer treatments is weak Reishi Mushrooms: Mechanism of Action Used as a dietary supplement in Chinese medicine to promote health and longevity Also known as the Ling Zhi or ‘Mushroom of Immortality’ 2 active compounds: triterpenes, and beta-glucan polysaccharides Mechanism of Action Inhibition of proliferation Apoptotic effect Induction of cell cycle arrest Inhibition of invasive behaviors Anti-angiogenesis Immunostimulating, Antioxidant properties Evidence based Efficacy Few human studies 2 studies noted improvement in immune stimulating effects on patients Most evidence is for chemotherapeutic support i.e. reduction in CTX related nausea and vomiting Safety Can cause respiratory allergic reactions, dry mouth, throat, and nasal passages, bloody diarrhea, dizziness, itchy skin Can interact with antibiotics, anticoagulants, antiHTNs, immunosuppressants, CTX agents, and sedatives Bottom Line There are few human studies Reishi mushrooms may have some immune enhancing effect, but more research is required. Risk for multiple drug interactions Natural Health Product Safety & Drug Interactions Interactions with anticancer drugs-all aspects of pharmacokinetics may be affected Importance of P450 cytochrome enzymes, particularly CYP3A4 that oxides many anticancer agents Risk of induction- increase CYP activity or inhibition-lower CYP activity Potential effect on gut wall metabolism and liver 1st pass effect NHPs and CTX and RTX Very controversial—a conundrum! Two divided camps: Cons: we have reviewedPros: Reactive oxygen species (ROS)normal metabolic byproducts essential for life They are essential for various cell defense mechanisms, but can cause oxidative damage to DNA, proteins, & lipids NHPs and Chemotherapy Administration of chemotherapeutic agents results in a greater degree of oxidative stress than is induced by the cancer itself Oxidative stress reduces the rate of cell proliferation-may interfere with CTX which depend on the rapid proliferation of cancer cells for optimal activity High oxidative stress can increase lipid peroxidation which can interfere with CTX NHPs and Chemotherapy Lipid perioxidation generates aldehydes which can inhibit drug induced cell death Proponents suggest use of antioxidants during CTX reduces lipid peroxidation and aldehydes, therefore, is of benefit Must consider the oxidative stress capacity of the CTX agents-some generate high levels of oxidative stress, others low levels. NHPs and Chemotherapy Systematic review (July 2000-January 2002)—individual antioxidant vitamin supplements do not reduce toxicity associated with anticancer therapyMore potent antioxidants or higher doses of individual antioxidants required?-role of timing? NHPs and Chemotherapy Increasing studies on Chinese medical plants that contain phenolic compounds such as phenolic acids, flavonoids, tannins, coumarins, lignans, quinines, stilbenes, curcuminoids Many showing positive effects on carcinogenesis Image removed due to copyright NHPs and Radiotherapy Minimal studies on same Mixed opinions similar to CTX i.e. ConRT relies on free radical generation and ROS for its effect—antioxidants may reduce ROS Pro—radiotherapy is most effective in well oxygenated tissues-antioxidants may improve blood flow within tumors and surrounding tissues NHPs-Drug Interactions Some herbs possess antiplatelet activity, interact with corticosteroids, CNS drugs, product hepatotoxicity, nephrotoxicity, plus have additive effects with opioids **Anticoagulant effects-Gingko, Garlic, Ginseng Avoid with thrombocytopenia, other anticoagulants, in the perioperative period Acupuncture According to Traditional Chinese Medicine (TCM)- one of the most common causes of pain is the ‘stagnation of qi, blood, and phelgm’ along the acupuncture meridians or channels acupuncture attempts to unblock the stagnation Acupuncture Acupuncture analgesia may be initiated by stimulation of the small afferent sensory nerve fibers in muscle-----> spinal cord------> midbrain-------> pituitary gland Results in release of endogenous opioids such as endorphins, enkephalins, and monoamines Acupuncture Most patients appears to obtain moderate to above average effects from acupuncture, although duration of response varied, ranging from hours to several months, tx frequencies and duration of tx were also variable--multiple txs often required to sustain pain relief Acupuncture Patients reporting relief: malignant abdominal pain, bone metastases, and myofascial pain In some studies, patients used fewer analgesics, with improved mobility and ability to complete their activities of daily living Electroacupuncture appears to be of benefit for bone metastases Image removed due to copyright Image of man with multiple needles in head Image removed due to copyright Image of acupuncturist with needles Image removed due to copyright Image of patient receiving electroacupuncture Image removed due to copyright Image of man receiving cupping on back Image removed due to copyright Image of man after cupping Image removed due to copyright Image of man receiving moxibustion Acupuncture for other symptoms Nausea and Vomiting: best evidence for CTX related- Electroacupuncture for CTX acute vomiting Acupressure for CTX acute nausea Minimal effect on delayed CTX nausea and vomiting Dyspnea, Fatigue-few studies-mixed results Mind-Body Therapies/Relaxation Therapies Include Hypnosis, Meditation, and Guided Imagery These techniques, as a group, alter sympathetic activity (likely via changes in catecholamine levels or other neurochemical systems) with decreases in oxygen consumption, respiratory and heart rates, and blood pressure Hypnotherapy and Guided Imagery Strong evidence for use of hypnosis in alleviating cancer pain, CTX induced nausea and vomiting, anxiety, surgical and procedural pain May do so by immune enhancement due to a change in psychological state, a change in neurological arousal (relaxation response) and change in consciousness Meditation including Mindfulness Based Stress Reduction (MBSR) Effective for cancer pain, psychosocial distress, sleep problems, improve QoL Much work done at the Tom Baker Cancer Centre in Calgary on MSBRinvolves staying focused on the present, breathing exercises—Dr. J. Kabat-Zinn Massage +/Aromatherapy Multiple studies in cancer patients have found that massage appears to alleviate pain, reduce anxiety, depression, stress, and fatigue But, lack of rigorous research prevents drawing definitive conclusions Research on aromatherapy and aromatherapy/massage in cancer pain has yielded mixed results Reflexology Is a form of foot massage designed to harmonize bodily functions and thus have a healing and relaxing effect. Based on the premise that there are reflex areas in the feet and hand that correspond to all the glands, organs and parts of the body Is used to relieve stress, tension, improve blood supply and promote homeostasis Reflexology Few studies Cancer pain studies suggest that foot massage and reflexology both appear to decrease perceptions of pain and induce relaxation Energy Healing Techniques: Reiki and Therapeutic Touch (TT) Involves placement of hands (Reiki) or no touch (TT) on the body to detect and unblock areas of stagnant qi or blocked energy Practitioners hypothesize that this therapy re-establishes the energy balance in areas of the body experiencing disease and discomfort---> promotes healing, reduces pain and improves QOL Reiki An Edmonton study! Randomized trial compared pain, QoL, and analgesic use in 24 patients with cancer pain Received standard opioid management plus rest or with Reiki Results: Patients who received Reiki experienced improved pain control, and QoL but with no change in opioid use between the groups What we covered….. 1. Reviewed several natural health products for cancer prevention and treatment 2. Discussed the potential for NHPs to interact with other medications including CTX and RTX 3. Reviewed the use of and evidence base for other complementary therapy modalities in cancer and supportive care management Thank you Questions or Comments?