Transcript Slide 1
Ms. Cindy Manchulenko, RN, BN
Clinical Research Nurse
Vancouver General Hospital
Objectives
Provide an overview of the most common
side effects in multiple myeloma:
Peripheral Neuropathy
Constipation/Diarrhea
Rash
Thrombosis (Blood clots)
Anemia and Fatigue
Learn how to manage these side effects
Peripheral Neuropathy
Peripheral Neuropathy
Presenting signs and
symptoms
Numbness
Weakness (usually mild)
Autonomic symptoms
Balance concerns
Neuropathic pain
Peripheral Neuropathy
What causes PN?
Velcade (bortezomib)
Thalidomide (Revlimid – rare)
Spinal cord compression
Other co-morbidities - diabetes
PN : Symptom Management
For Velcade, Thalidomide or Revlimid
Hold drug until nerve pain resolves, then dose reduce
Velcade : can switch to once weekly dose instead of
twice weekly
Spinal Cord Compression
Your doctor will do a CT scan to check for this, and
radiation treatment may be needed
Other Co-Morbidities : Diabetes
Monitor your blood sugar regularly especially if you’re
also taking steroids
PN : Symptom Management
Medications
Drugs will be useful in patients who have
neuropathic pain
Symptomatic treatment, does NOT reverse
the neuropathy
Three classes of drugs are typically used
Antiepileptics
Antidepressants
Analgesics (cannabinoids, opioids, tramadol)
PN : Symptom Management
Medications : Antiepileptics
Gabapentin (Neurontin)
Pregabalin (Lyrica)
Both have the SAME mechanism of action
One is not better than the other
The switch from one to the other is useful
when patient is intolerant to one molecule
Gabapentin Titration Schedule
Initiation of Treatment
Day Day Day
1
2
3
TID
schedule
AM
PM
hs
Day Day Day
6
9
12
300
300
300
600
300 300
300
600
600
300 300 300
600
600
600
Maintenance (mg) 1800 mg / day = AVERAGE effective dose!
Can further titrate to 3,600 mg/ day
PN : Symptom Management
Medications : Pregabalin (Lyrica)
Titration similar to gapapentin
Start with 25-50 mg twice daily and increase
by 25-50 mg/day every 1-3 days
Typical dose 100-150 mg twice daily (Max
300 mg twice daily)
Peripheral edema common with pregablin,
less frequent with gabapentin
Beware of renal failure (CrCl < 60 mL/min)
Medications:
Gabapentin and Pregabalin
Common side effects
Drowsiness
Dizziness
Nausea / Vomiting / Constipation
Peripheral edema
Asthenia
These drugs CANNOT be stopped abruptly
as withdrawal symptoms will appear
Taper slowly over a few weeks
Elderly patients (>65) are more susceptible
to adverse effects
Medications:
Tricyclic Antidepressants (TCA)
Amitriptyline, nortriptyline, imipramine,
desipramine, doxepin
Doses range from 10 to 150 mg/day
Typically given at bedtime when once a
day dosing used (up to 50 mg), otherwise
given in multiple doses
Medications:
Tricyclic Antidepressants
Side effects:
Drowsiness, dry mouth, urinary retention,
confusion, nausea, vomiting, constipation
Elderly are at high risk for side effects
May cause cardiac toxicity
Best used when both psychiatric symptom
(insomnia, depression, anxiety) AND
neuropathic pain are present
Medications: Analgesics
Topical analgesics: do not work effectively,
do not use for this indication
Cannabinoids:
Nabilone (Cesamet®), Dronabinol (Marinol®),
Dronabinol/cannabidiol (Sativex®), Marijuana
Cesamet® and Marinol® are approved as
antiemetics
Sativex® for cancer pain
Should be prescribed by pain care specialists
Medications: Analgesics
Opioids
Morphine, fentanyl, hydromorphone, codeine
Less effective than antiepileptics for PN
Unfavourable side effect profile
Tramadol
Interesting option, has opioidergic effect and an
effect on neuropathic pain
No dependency
Less constipation than with typical opioids
Tramacet (tramadol 37.5 mg/acetaminophen 325
mg) 1-2 tablets every 6-8 hours, maximum 8
tablets/day
PN : Symptom Management
Nutritional Supplements
Data are anecdotal, prospective studies are needed
Multi-B complex vitamins
Folic acid to facilitate B12 action
Vitamin E to assist vascular integrity and blood flow
to extremities
Amino acids (i.e., acetyl L-carnitine or alpha lipoic
acid)
Cramps: Mg & K+ if low
Tonic Water
PN : Symptom Management - Other
Cocoa Butter: Rich in Vitamin E and other emollients,
apply to affected area twice a day with gentle massage
Creams with menthol or spearmint
Keep feet elevated during the day if sitting
Constipation
Causes:
Velcade, Thalidomide, Revlimid
Sedentary lifestyle
Dehydration
Symptom Management:
Constipation
Diet (e.g. high-fiber foods, such as flaxseed meal,
prunes, prune juice, blueberries)
Plenty of fluids – at least 1.5 liters/day (or eight 8oz
glasses of water/day)
Exercise – walk!
Medications:
Colace (docusate) 100-200mg once or twice per day
Senokot 1 or 2 tabs at bedtime
Lactulose or Milk of Magnesia 15mL’s – 30mL’s up to 3 times per
day.
Diarrhea
Causes :
Velcade
Revlimid
Dexamethasone
Chemotherapy
Symptom Management:
Diarrhea
Plenty of fluids – with electrolytes (salts)
Gatorade, Pedialyte
BRAT Diet : bananas, rice, applesauce and toast
Fiber or natural bacterial flora supplements
(Benefiber, Activia yogurt, acidophollus)
Medications: Immodium 2mg up to max 8mg per
day.
Rashes
Causes:
Velcade
Revlimid
Thalidomide
Shingles infection
Shingles (Herpes Zoster)
Maculopapular (flush to
skin & also raised lifted off
the skin) vesicular
eruptions
Tends to be very painful
Can occur at any time
®
Velcade
Rash
Truncal and upper extremity
maculopapular rash
Not painful, some pruritus
Biopsy by derm confirms
diagnosis
May wax and wane
throughout treatment
Bortezomib treatment can
continue
®
Revlimid
Rash
Maculopapular, or scaly red
erythema
Tends to start out in the legs
and move up
Pruritus usually associated;
not painful unless Gr.3 or
more
Symptom Management : Rashes
Prophylaxis for shingles
Valtrex® (valacyclovir) or acyclovir during Velcade®
treatment
Shea butter or cocoa butter or other
moisturizer for extreme dryness
Dose reduce medication if more than 50%
of body surface area is affected
Symptom Management : Rashes
Treatment of itchiness associated with
rash
Antihistamine
Benadryl® 25-50mg PO Q 4-6h as needed
Atarax® 10-25mg PO Q 6-8h as needed
Side effects : drowsiness, dry mouth, may
exacerbate glaucoma; elderly more susceptible
Hydrocortisone cream (0.5-1%) or other topical
steroid to affected areas
OTC formulation available
Thrombosis
Virchow’s Triad
Venous stasis
Hypercoagubility
Trauma to vessel wall
Virchow’s Triad
Thrombosis
Identified by Professor Armand Trousseau
in 1865
Incidence of VTE varies in tumor type and
treatment
exacerbated by central lines
chemotherapy
hormonal therapy
surgery
erythropoiesis stimulating agents (ESAs)
Take a Guess
What is the background incidence of
thromboembolic events in patients with
multiple myeloma?
— 5-10%
— 15–20%
— 25–30%
— 35–40%
Myeloma & Thromboembolic
Complications
Incidence of Thromboembolic Events
Background incidence in myeloma
5-10%
Thalidomide
Dexamethasone
Thal/dex
MPT vs MP
MPT vs MP vs iv Melphalan
Thal/anthracyclines
Lenalidomide/dex
Lenalidomide/dex + ESA
Zonder JA. Hematology. (Am Soc Hematol Educ Program) 2006:348–355
Rodeghiero et al. Pathophysiol Haemost Thromb 2003;33(suppl 1):15–18
Niesvizky et al. ASCO 2006 (abstract 7506)
3%
3%
10-20%
17% vs 2%
12% vs 4% vs 8%
10-58%
16%
23%
Bortezomib in Combination?
No VTEs in patients receiving VMPT and VMDT
Preliminary suggestion that bortezomib with
lenalidomide has lower incidence of VTE vs
lenalidomide alone
Further studies are needed to investigate this
possible protective effect of bortezomib
Richardson et al. Blood 2006;108 (Abstract 405)
Palumbo et al. Blood 2006;108 (abstract 407)
Terpos et al. Blood 2006;108 (abstract 3541)
Signs and Symptoms: Thrombosis
Assess for:
pain or swelling in limbs
chest pain (worse with inspiration)
shortness of breath
Symptom Management: Thrombosis
Prevention : baby aspirin once daily (for Revlimid
and Thalidomide only)
Low-molecular weight heparin used as it has half the
risk of recurrence as oral anticoagulant in cancer
pt’s. (9% vs 17%)
Fragmin® 200 IU/kg s/c OD for 1st month
Only LMWH have an indication in cancer patients
Side effects : bleeding, sensitivity at the injection
site
Symptom Management: Thrombosis
Warfarin (Coumadin®) may also be used at the
physician’s discretion
Target international normalized ratio (INR)
Warfarin’s activity is affected by chemo, pulse
dexamethasone, variable food intake
Our patients are NOT the best candidates for
warfarin therapy
Anemia and Fatigue
Cancer Related Fatigue
70-100% of cancer patients are
fatigued1
Most common & distressing
symptom experienced during
treatment2
30 to 75% of cancer survivors
continue to report fatigue
symptoms months to years after
treatment ends3
1 NCCN-Cancer-Related
Fatigue, Clinical Practice Guideline in Oncology- v 2.2005:p.MS-1-2 2 Stricker C, Drake D, Hoyer K et al: Evidencebased practice for CRF management in adults with cancer: exercise as an intervention, Oncology Nurs Forum 32(3): 663-639, 2005.
3.NCCN-Cancer-Related Fatigue and Anemia,Treatment Guidelines for Patients-Version III/Nov.2005:pg6
Defining Cancer-Related
Fatigue
A persistent, subjective sense of tiredness
related to cancer or cancer treatment that
interferes with usual functioning”1
Often unexpected and remains unrelieved by
sleep, or by change in routine2
Caused by the malignancy and by the
treatments for that malignancy2
1.
NCCN-Cancer-Related Fatigue, Clinical Practice Guideline in Oncology- v 2.2005:p.FT-1
2.
Martha E. Langhorn, Janet S. Fulton, Shirley E. Otto, Oncology Nursing, Fifth Edition, Mosby 2007, p 661
Presenting Signs & Symptoms
Patients may describe the following:
Lack of energy
Feeling like “I can’t be bothered to do much”
Problems sleeping
Finding it hard to get up in the morning
Muscle pain
Being short of breath after doing small tasks
Brochure: Your Bank to Energy Savings: Helping people with cancer handle fatigue, Ortho-Biotech, March 2008
Presenting Signs & Symptoms
Patients may describe the following:
Feeling anxious or depressed
Finding it hard to concentrate
Being unable to think clearly or make
decisions easily
Loss of interest in doing things they usually
enjoy
Negative feelings about self or others
Brochure: Your Bank to Energy Savings: Helping people with cancer handle fatigue, Ortho-Biotech, March 2008
Fatigue is under-reported by
Patients
Fear of alteration in treatment
Poor recognition of a slow and gradual change in
personal energy level
Disconnect between physician and patient
perception of fatigue
Believe that physicians have more important
things to worry about
Unaware of treatment availability
1. NCCN-Cancer-Related Fatigue and Anemia Treatment Guidelines for Patients-Version III/Nov.2005: pg MS-4
Defining Chemotherapy-Related
Anemia
Caused by the
myelosuppressive
effects of
chemotherapy
NORMAL
ANEMIA
NCCN Practice Guidelines in Oncology – v.1.2007. Cancer-and Treatment Related Anemia.
Anemia of Myeloma
Inadequate red blood cell (RBC) production
Shortened RBC survival
Bone marrow failure to compensate by increasing RBC
production
Depressed RBC production is multifactoral
Common Causes:
cytokine inhibition of erythropoiesis
low serum erythropoietin levels (often caused by
associated renal impairment) are the common causes
Goals of Interventions
Detect & correct underlying problem
Chemotherapy-induced anemia
Treat infection
Correct fluid and electrolyte problems
Correct hormone imbalances
Correct metabolic and nutritional problems
Treat clinical depression
Optimize management and minimize selfcare burden
Nutritional Counselling
Individuals with cancer may experience
changes in nutrition
Their ability to process nutrients
Their need for increased energy
requirements
Decreased intake of food, fluids and certain
nutriments
Iron, vitamin B12 and folic acid are
important
NCCN-Cancer-Related Fatigue and Anemia,Treatment Guidelines for Patients-Version III/Nov.2005:pg 10; All about Anemia, Fatigue and Cancer p. 17
Iron Supplementation
Iron rich foods
Hemoglobin could increase significantly if
vitamin C is added to iron-rich food
Iron-rich foods to improve diet:
Red meat (beef, pork, game), poultry, fish,
clams, oysters
Dark green leafy vegetables
Whole grains, iron fortified breads and
cereals
Hillman RS, Ault KA & Rinder HM. (2005) Hemotology in Clinical Practice (4th Ed.) Toronto, Ontario, McGraw-Hill
Iron Supplementation
Pros and cons of oral iron therapy
Advantages
Easy to administer (oral)
Disadvantages
Nausea, vomiting, dyspepsia, constipation,
diarrhea, drug interactions , dark stools
Patients should take iron on an empty
stomach
Continue Treatment for 6-12 months after
normalization of Hb
Vitamin B12 Supplementation
Vitamin B12 Deficiency
Deficiency usually due to malabsorption
2.0 - 2.5µg daily needed
Meat/diary are main sources
Animal products (poultry, beef liver, cheese,
eggs)
Crustaceans (clams, crab, shrimp)
Fish (salmon, sardines)
Vitamin B12 fortified breakfast cereals and soy
beverages
Hillman RS, Ault KA & Rinder HM. (2005) Hemotology in Clinical Practice (4th Ed.) Toronto, Ontario, McGraw-Hill
Oh RC & Brown DL. Vitamin B12 Deficiency. American Family Physician, 2003;67(5)
Vitamin B12 Supplementation
Treatment
Vitamin B12 – Find out why (Vegan, GI tract
pathway inability to absorb)
Usually requires lifelong supplementation
Parenteral supplementation 100-10,000ug
IM monthly
Hillman RS, Ault KA & Rinder HM. (2005) Hemotology in Clinical Practice (4th Ed.)
Toronto, Ontario, McGraw-Hill
Folate Supplementation
Nutritional Deficiency Factors
Consider excessive alcohol intake,
malabsorption,
50µg daily needed
Folate obtained from fruits/vegetables
Oral folate; 1mg po daily; OTC
Severe deficiency in hemolytic anemia
Treat for 3-6 months beyond normal
hemoglobin
Erythropoietins
Epoetin alfa (EprexTM)
Recombinant human erythropoietin, identical to
the endogenous molecule
Dosed at 40,000 U QW by subcutaneous
injection.
Darbepoetin alfa (AranespTM)
Indicated for the treatment of chemotherapyrelated anemia
Glycosylated erythropoietin (has extra
carbohydrate moieties on the molecule)
Dosed 2.25 mcg/kg QW by subcutaneous injection
or 500 mcg Q3W
Blood Transfusions
Advantage:
Rapidly corrects severe anemia
Disadvantages:
Short-lasting effect
Transfusion risks & reactions
Time to receive unit/s of blood
Time spent by healthcare providers (nurses,
pharmacists, physicians, other staff) in carrying out
the procedure, and time spent by the patient
Associated cost of the procedure
All About Anemia, Fatigue and Cancer. p.18
Nutritional Support
Assess nutritional intake/appetite or weight
changes
Address electrolyte imbalances
Reinforce the need for proper nutrition and
hydration
Assess needs for supplements
Tell patient not to diet
Consult dietician
1. http://www.bccancer.bc.ca/PPI/copingwithcancer/symptoms/fatigue/pmgt/htm
Patient and Family Education
Patient Education & Information
Provision
Those who learn about fatigue before they
experience it have lower incidences of fatigue and
are able to manage it better1
Instruct patient & family:
factors that contribute to fatigue
recognize the signs of fatigue
how to manage fatigue
1. http://www.bccancer.bc.ca/PPI/copingwithcancer/symptoms/fatigue/pmgt/htm
Energy Conservation
Encouraged to set priorities,
delegate tasks
Schedule activities – Peak hours
Plan daily routines
Identify which activities are most taxing
and which tasks can be postponed
Help identify alternative ways of doing
tasks
Martha E. Langhorn, Janet S. Fulton, Shirley E. Otto, Oncology Nursing, Fifth Edition, Mosby 2007, p 666
Sleep and Rest
Good sleep hygiene
Go to bed at same time every night
Limit sleep interruptions
Avoid stimulants prior to sleep
Use hypnotics appropriately
Relaxation and imagery
http://www.bccancer.bc.ca/PPI/copingwithcancer/symptoms/fatigue/pmgt/htm
Stress Management/
Psychosocial Support
Being anxious/upset about having cancer
is “normal”
You are not alone in your feelings
Encouraged to maintain the patterns you
had prior to diagnosis
Practice meditation, deep breathing, or
relaxation techniques.
http://www.bccancer.bc.ca/PPI/copingwithcancer/symptoms/fatigue/pmgt/htm
Exercise
Exercise improves QOL/reduces fatigue1
Base prescription on individual assessment of
functional capacity and limitations2
Start slowly; increase activity over time
Regular, mild to moderate activity is better than
infrequent, intense workouts3
Choose activities that fit lifestyle3
Plan exercise at regular times, and when you
have the most energy3
1. Martha E. Langhorn, Janet S. Fulton, Shirley E. Otto, Oncology Nursing, Fifth Edition, Mosby 2007, p 666
2. Camp-Sorrell D, Hawkins R A, Clinical Manual for the Oncology Advanced Practice Nurse, Second Edition, Oncology Nursing Society, 2006, pp 131.
3. Your Bank to Energy Savings: Helping people with cancer handle fatigue, Ortho-Biotech, March 2008
Social Support
Family, friends and community groups can
help manage fatigue
Encourage patients to accept offers of help
Delegate tasks
Have someone come with patient to
appointment
Hire someone to do yard work or chores
Home care services
Tell them to talk to their health care team!
http://www.bccancer.bc.ca/PPI/copingwithcancer/symptoms/fatigue/pmgt/htm
Summary
Most Common Side effects in Myeloma
Peripheral Neuropathy
Constipation/Diarrhea
Rash
Thrombosis (Blood clots)
Anemia and Fatigue
Summary
If you are experiencing any side effects, tell
your doctor and/or nurse
Listen to your body
When people offer to help you, take it!
Hydrate, hydrate, hydrate