Transcript 00024 - CAM in UME Project

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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
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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
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Natural Health Products- A Taste
Prevention
Green Tea
Soy Products
Generalized Cancer Treatment
Mistletoe
Reishi Mushrooms
Specific to Cancer
Pain and Other
Symptoms
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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
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Inhibit inflammatory cytokines
related to carcinogensis
Inhibition of angiogenesis
Inhibition of urokinase involved
in metastases
Antioxidant reducing DNA
damage
Evidence Based
Efficacy
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Cochrane Collaboration Systematic
Review (2009)
51 studies reviewed, 1.6 million
participants
Mainly observational studies with medium
to high methodological quality
Evidence based Efficacy
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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
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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
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Bottom Line
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Inhibition of proliferation
Apoptotic effect
Induction of cell cycle arrest
Inhibition of invasive behaviors
Anti-angiogenesis
Immunostimulating, Antioxidant
properties
Evidence based Efficacy
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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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
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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)
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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
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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?