TREATMENT INTERACTIONS &TODAY’S MYELOMA PATIENT
Timothy Tyler, Pharm.D., FCSHPDirector of Pharmacy Services
Comprehensive Cancer Center
Desert Regional Medical Center
Objectives
Understand at a basic level, the complexity of current treatments for Multiple Myeloma
Review major interactions and cautions with standard and complementary treatments
Review specific oral supplements of concern Focus on appropriate sources of information Have Fun (that’s okay – really!)
Comprehensive Cancer CenterDesert Regional Medical CenterComprehensive Cancer CenterDesert Regional Medical Center
Comprehensive Cancer Center Established in 1990 – 21st year of operation Part of 5 cancer center chain (CA / FL / NY / NJ) DRMC-CCC began a CAM team in 1999 Presented 6 month study at ISOPP VII (Prague) CAM team established weekly meetings 2000 Team is composed of a Physician, Physiologist,
Pharmacist, Dietician, Social Worker Patient satisfaction survey results demonstrate
ongoing satisfaction with service
CAM = Complementary & Alternative Medicine
The Desert Experience 108 cancer patients from a single physician
surveyed from 1/99 through 6/99 Brief patient interview with a questionnaire Overall 85% prevalence rate in CAM usage About 50% of which was multivitamins or
multivitamin w/ mineral supplement Information not volunteered prior to survey
CAM = Complementary & Alternative Medicine
The Desert Experience
85% used at least one form of CAM (includes multivitamin, +/- mineral combination)
52% of those using CAM take only a multi-vitamin, +/- mineral combination
29% used herbal preparations 13% used food derivatives/supplements 9% used (other) complementary therapies
CAM = Complementary & Alternative Medicine
Possibly Unrealistic Goals …According to the late Varro Tyler, Ph.D., Sc.D. and professor emeritus of pharmacognosy at the School of Pharmacy at Purdue University, people do set somewhat unrealistic treatment goals. If people do set unrealistic goals for themselves as it pertains to herbal products, many time they verge on “paraherbalisim – the belief in the superiority of anything natural and organic”. The most dangerous misconception that this concept brings is that natural substances cannot cause harm. Tyler warns that “some highly toxic substances are derived from plants.”
Foreman J. The Boston Globe 3/17/97
Traditional Oriental Medicine (TOM) “Traditional” medical in such places such as:
China, Japan, Cambodia, Korea, and Vietnam Basic principles:
Five elements of wood, fire, earth, metal, and water. Tao = “the way”, significance of change & process Yin & Yang = 2 opposing forces that drive change Ch’i = invisible universal energy force that is believed to flow
through all living organisms. Acupuncture = opens the meridians and/or directing the flow of
ch’i to promote health
Combines diet, acupuncture, meditation, physical exercise, healing exercise, herbal medicine, and massage to promote health.
Acupuncture NIH supports efficacy in the control of:
Chemotherapy-related nausea & vomiting Palliation of chronic pain
Studies suggest that it is reasonable to accept the use of acupuncture in conjunction with a standard antiemetic to control chemotherapy-related nausea and cancer-related pain.
NIH = National Institute of Health
Acupuncture Caution should be exercised in patients with:
A compromised immune system Affected limb of someone who has a lymph node
dissection (impaired lymphatic drainage)
Avoid insertion of needles in patients who are: Thrombocytopenic (low platelet counts) Using anticoagulant therapy (warfarin, aspirin, etc)
Manual Healing Methods Touch and manipulation, used for hundreds of
years in the medical profession Hippocrates discussed the benefits of therapeutic
touch with students Three types:
Massage Bodywork Chiropractic
Use with extreme caution with bone pain and bone disease – particularly with Multiple Multiple MyelomaMyeloma
Massage Involves manipulation of soft tissues Benefits may include:
stress aches & pain Improved circulation Lymph movement & motility Enhanced digestion & intestinal function General relaxation
Massage Studies Results … Inconclusive for relief from cancer-related pain Evidence does not indicate promotion of tumor
metastasis at this time 1 trial showed that massage reduced nausea in
patients undergoing autologous (self) BMT 2 trials found manual lymph drainage to be
effective with compression bandaging or sleeves in patients with arm lymphedema after surgery for breast cancer
BMT = Bone Marrow Transplant
Massage Studies have shown that massage can be helpful
in treating pain, anxiety, depression, and lethargy Concerns:
Patients who are prone to bleed, thrombocytopenic or receiving anticoagulation therapy
Deep abdominal massage has been associated with internal bleeding
Avoid over stents or other prosthetic devices Multiple Myeloma patients have greater fracture risk
Agents Used in Multiple Myeloma IV CHEMOTHERAPY Bortezomib (Velcade) Carmustine (BCNU) Cyclophosphamide (Cytoxan) Doxorubicin, Lipo. (Doxil) Melphalan (Alkeran) Vincristine (Oncovin)
ORAL CHEMOTHERAPY Dexamethasone (Decadron) Lenadiomide (Revlamid) Melphalan (Alkeran) Prednisone (Deltasone) Thalidomide (Thalamid)
SUPPORTIVE CARE Pamidronate (Aredia) Zolendronic Acid (Zometa)
NOTE = Agents Listed are FDA-Approved (excluding compendia) for the treatment of Multiple Myeloma
Antioxidants vs. Chemotherapy
To date, no definitive studies in humans have demonstrated long term effects of combining oral antioxidants and chemotherapy. There is sufficient cause for concern regarding potential interactions and it should be possible to predict obvious interactions and suggest where caution should be exercised. Improving short-term tolerance should not come at the expense of decreased effectiveness.
Oncology – July 1999
Bortezomib + Green Tea = Bust Green tea contains powerful polyphenols such as
epigallocatechin gallate (EGCG) Preliminary research in vitro and in vivo shows green
tea polyphenols interact with Bortezomib (Velcade) and other proteasome inhibitors.
The result is blocking the proteasome inhibitory effects such that cell death is not induced in multiple myeloma or glioblastoma cancer cell lines.
Patients taking boronic acid-based proteasome inhibitors like Bortezomib (Velcade) should not take green tea.
Source = Natural Medicines Database
St. John’s Wort = No Way Jose St. John's Wort induces liver enzymes thus making it
problematic and somewhat patient variable Drugs that might be affected include Chemotherapy
agents Etoposide, Paclitaxel, Vinblastine, Vincristine. In addition, pain medications, steroids, antiemetics,
antidepressants, OTC acid blockers and numerous others are impacted
Interaction Rating = Major (Do not take) Severity = High Occurrence = Probable Level of Evidence = B
Source = Natural Medicines Database
Cyclophosphamide + Astragalus = ? Be cautious with taking Cyclophosphamide (Cytoxan) + Astragalus
in combination Some evidence suggests astragalus might reduce
immunosuppression caused by Cyclophosphamide Astragalus seems to stimulate immune function so theoretically,
taking Astragalus might decrease the effects of immunosuppressive therapy such as steroids and chemotherapy like Cyclophosphamide
The problem stems from when the treating clinician does not know the patient is taking an immunomodulator
In addition to Astragalus, Alfalfa, Ashwagandha, Cat’s Claw, Echinacea and about 38 other immunostimulants should be used only after gaining approval from your doctor
Source = Natural Medicines Database
Chemotherapy + Alpha Lipoic Acid
Theoretically, use of Alpha Lipoic Acid (ALA) might decrease the effectiveness of chemotherapy.
Preliminary evidence from an unpublished study suggests antioxidants may decrease the effectiveness of chemotherapy
Natural Medicines Database listed this for Bortezomib, Carmustine, Doxorubicin, Cyclophosphamide, Melphalan, Vincristine
Source = Natural Medicines Database
Chemotherapy + Enzyme CoQ10 Theoretically, taking Coenzyme Q-10 supplements
might prevent cardiotoxicity induced by Doxorubicin & Cyclophosphamide
But there is also concern that coenzyme Q-10 might lower effectiveness of doxorubicin by protecting tumor cells from chemotherapeutic agents that work by inducing oxidative stress
Similar concerns exists for the alkylating agents such as Cyclophosphamide and radiation therapy
Source = Natural Medicines Database
Vitamin C and The Big ‘C’ Dr. Linus Pauling
advocated in the 1970’s 3 trials to date using
10,000 mg daily No difference in patient
survival has been seen Therapy with mega doses
are not benign
Oncolink Website 3/17/2000
Vitamin C and The Big ‘C’ The use of antioxidants like Vitamin C during chemotherapy
remains controversial There's concern that antioxidants could reduce the activity of
chemotherapy drugs which generate free radicals Mechanisms other than the antioxidant effects of vitamin C might
be involved. This might include prevention of the damaging to the cell powerhouse (mitochondria) caused by many chemotherapy drugs, which is involved in regulating cell death
In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells
More evidence is needed to determine what effects vitamin C has on chemotherapy. Advise patients to consult their oncologist before using vitamin C supplements, especially in high doses.
Source = Natural Medicines Database
Chemotherapy + Vitamin E The use of antioxidants like vitamin E during chemotherapy remains
controversial. There's concern that antioxidants could reduce the activity of
chemotherapy drugs which generate free radicals, such as Cyclophosphamide, Carmustine, and Doxorubicin
However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells
More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy
Natural Medicines Database advises patients to consult their oncologist before using vitamin E supplements, particularly when considering high doses especially with bleeding risks or surgery
Source = Natural Medicines Database
Acceptable CAM Treatments Nutrition – Fluid, Protein, Fat, MVI (RDA)
Variety of fish (Omega 3 FA) 2-3 servings/day Soy in form of food 1-2 tablespoonfuls daily ground Flaxseed
Certain herbal products – consulted & supervised Acupuncture for N/V and pain Massage for anxiety and pain (Physician willing) Moderate exercise (Physician willing) Psychological and mind-body therapies
Source = Comprehensive Cancer Center CAM Team
Top 12 Notes on Medicinal Herbs
Doctors should be asking you about your use of herbs/supplements If they don't – volunteer the information especially when on
treatment Natural does not mean safe (strychnine is natural) Lack of standardization: contents and efficacy may vary with brands Lack of quality control/regulation: contamination Do not use more than the recommended dose Herbals generally should not be used for more than several weeks Infants, children, and elderly should use with professional guidance Medicinal herbs should not be taken during pregnancy and lactation Avoid herbals that are known to have toxic/adverse side effects Accurate diagnosis and discussion of proven treatments are essential Stop all herbs at least 10 days prior to surgery
CAM or SHAM? Many have adopted a
“whatever works”“whatever works” philosophy of medicine
There are products that have documented aid
There are products with documented harm
There are products we don’t know much about
Web Surfing: Watch Four Red Flags One study suggests to avoid sites with one or more
of the following red flags: 1. Online purchase of described product is available.
2. Treatment description includes patient testimonials.
3. The treatment is described as a “cancer cure.”
4. The treatment is described as “having no side effects.”
The authors also point out that the absence of red flags isn’t necessarily a guarantee of scientific accuracy.
http://nccam.nih.gov
Created by congressional mandate in 1992 to “facilitate the evaluation of alternative medical treatment modalities”. Originally called the Office of Alternative Medicine, it was renamed the National Center for Complementary and Alternative Medicine in 1998. It is a division of the National Institute of Health, which is under the auspices of the Department of Health and Human Services.
Reasons People with Cancer Choose CAM Making Choices What is Complementary and Alternative Medicine Types of Complementary and Alternative Medicine Talk with Your Doctor Before You Use CAM Natural Does Not Mean Safe! Choose Practitioners with Care Getting Information from Trusted Sources Resources
Questions to ask about a Web site: Who runs and pays for the site? Does it list any credentials? Does it represent an organization that is well-known & respected? What is the purpose of the site, and who is it for? Is the site selling or promoting something? Where does the information come from? Is the information based on facts or only on someone's feelings / opinions? How is the information chosen? Is there a review board or is the content reviewed by experts? How current is the information? Does the site tell when it was last updated? How does the site choose which other sites to link you to?
Elements of good information:
Also Known As (AKA) Scientific Names (geekius herbifora) People Use This For (you’d be amazed) Safety Profile (MANDATORY):
Likely SafeLikely UnsafeDefinitely Unsafe
More good Elements: Effectiveness:
Likely Effective for…Likely Ineffective for…Unknown efficacy ?
Mechanism of Action Adverse Reactions Dosage and Administration References
Nothing Exists in a Vacuum Interactions with Herbs & Supplements Interactions with Drugs Interactions with Foods Interactions with Lab Tests Interactions with Diseases or Conditions Interactions with pocketbook!!!pocketbook!!!
Good CAM/Drug Information
Until there is a cure … There is the IMF
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