Ms. Cindy Manchulenko, RN, BN
Clinical Research Nurse
Vancouver General Hospital
Objectives
 Provide an overview of the most common
side effects in multiple myeloma:
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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
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Numbness
Weakness (usually mild)
Autonomic symptoms
Balance concerns
Neuropathic pain
Peripheral Neuropathy
 What causes PN?
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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

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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

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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

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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

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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
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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
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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:


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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:
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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
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
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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

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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
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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