Ms. Cindy Manchulenko, RN, BNClinical Research Nurse

Vancouver General Hospital

ObjectivesProvide an overview of the most

common side effects in multiple myeloma:

Peripheral Neuropathy Constipation/DiarrheaRashThrombosis (Blood clots)Anemia and Fatigue

Learn how to manage these side effects

Peripheral Neuropathy

Peripheral Neuropathy Presenting signs and

symptomsNumbnessWeakness (usually mild)Autonomic symptomsBalance concerns Neuropathic pain

Peripheral NeuropathyWhat causes PN?

Velcade (bortezomib)Thalidomide (Revlimid – rare)Spinal cord compressionOther 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 CompressionYour doctor will do a CT scan to check for this,

and radiation treatment may be needed

Other Co-Morbidities : DiabetesMonitor 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

Day 1

Day 2

Day 3

Day 6

Day 9

Day 12

TID schedule

AM 300 300 300 600

PM 300 300 300 600 600

hs 300 300 300 600 600 600Maintenance (mg) 1800 mg / day = AVERAGE effective dose!

Can further titrate to 3,600 mg/ day

Initiation of Treatment

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 - OtherCocoa 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

ConstipationCauses:

Velcade, Thalidomide, RevlimidSedentary lifestyleDehydration

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.

DiarrheaCauses :

VelcadeRevlimidDexamethasoneChemotherapy

Symptom Management:DiarrheaPlenty of fluids – with electrolytes (salts)

Gatorade, Pedialyte BRAT Diet : bananas, rice, applesauce and

toastFiber or natural bacterial flora

supplements (Benefiber, Activia yogurt, acidophollus)

Medications: Immodium 2mg up to max 8mg per day.

RashesCauses:

VelcadeRevlimid ThalidomideShingles 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 GuessWhat 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%

ThalidomideDexamethasone

3%3%

Thal/dexMPT vs MPMPT vs MP vs iv MelphalanThal/anthracyclines

10-20%17% vs 2%

12% vs 4% vs 8%10-58%

Lenalidomide/dexLenalidomide/dex + ESA

16%23%Zonder JA. Hematology. (Am Soc Hematol Educ Program) 2006:348–355

Rodeghiero et al. Pathophysiol Haemost Thromb 2003;33(suppl 1):15–18Niesvizky et al. ASCO 2006 (abstract 7506)

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: Evidence-based 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

1. NCCN-Cancer-Related Fatigue and Anemia Treatment Guidelines for Patients-Version III/Nov.2005: pg MS-4

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

NCCN Practice Guidelines in Oncology – v.1.2007. Cancer-and Treatment Related Anemia.

Defining Chemotherapy-Related Anemia Caused by the

myelosuppressive effects of chemotherapy

ANEMIA

NORMAL

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

self-care burden

NCCN-Cancer-Related Fatigue and Anemia,Treatment Guidelines for Patients-Version III/Nov.2005:pg 10; All about Anemia, Fatigue and Cancer p. 17

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

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 beveragesHillman RS, Ault KA & Rinder HM. (2005) Hemotology in Clinical Practice (4th Ed.) Toronto, Ontario, McGraw-HillOh 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

chemotherapy-related anemia Glycosylated erythropoietin (has extra

carbohydrate moieties on the molecule) Dosed 2.25 mcg/kg QW by subcutaneous

injection or 500 mcg Q3W

All About Anemia, Fatigue and Cancer. p.18

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

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 6662. 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

SummaryMost Common Side effects in

MyelomaPeripheral Neuropathy Constipation/DiarrheaRashThrombosis (Blood clots)Anemia and Fatigue

SummaryIf you are experiencing any side

effects, tell your doctor and/or nurseListen to your bodyWhen people offer to help you, take

it!Hydrate, hydrate, hydrate