Managing Side Effects of Novel Agents
Kena C. Miller, RN, MSN, FNP
Roswell Park Cancer Institute, Buffalo, NY
A Presentation Developed by the International Myeloma
Foundation Nurse Leadership Board
Introduction to the International Myeloma
Foundation Nurse Leadership
Leadership Board
The IMF has formed a Nurse Leadership Board which
is made up of 20 expert
pp
nurses from around the United
States. Through their affiliation with myeloma
treatment centers, they have been chosen to assist in
dispersing information to
to patients,
patients, families and
and health
care providers dealing with multiple myeloma.
The following information is
is intended
intended to
to help
help you
you
better understand possible treatment options, side
effects to treatments and management of those side
effects. Please
Please be sure to consult your
your provider if you
have any questions or concerns regarding your
diagnosis, symptoms or treatment plan.
1
How Will Your Health Care Provider
Decide on Treatment?
· Treatment is individualized for each patient based
based
upon:
Physical exam and laboratory test results
Disease stage, symptoms and complications
at time of diagnosis
Whether the patient has been treated previousl
pp
y
for multiple myeloma
Age and general health
Lifestyle and quality of
of life
Information from current clinical trials
From International Myeloma Foundation. Multiple myeloma: patient handbook. 2006. IMF, North Hollywood, CA. www.myeloma.org
2
Goals of
of Treatment
Treatment
· Stop disease from damaging organs
· Extend length of time without evidence of disease
· Prolong life expectancy
· Relieve pain and other symptoms
· Maintain normal levels of activity and a good
quality of life
3
Treatments Used for Multiple Myeloma
· Chemotherapy (Drug therapy)
Conventional therapy:
· Steroids (Dexamethasone, Prednisone)
· Alkylating Agents (Melphalan, Cyclophosphamide)
· Anthracyclines (Doxorubicin, Liposomal doxorubicin)
Novel Therapy:
· Bt
Bort
i
ezom b
ib (V
(V l
e
d
ca
e )
· Thalidomide (Thalomid)
· Lenalidomide (Revlimid)
· Drugs are can be given alone or in combination
From International Myeloma Foundation. Multiple myeloma: Concise Review of the Disease and Treatment Options.
4
2006. IMF, North Hollywood, CA. www.myeloma.org
Treatment for Multiple Myeloma
(continued)
continued
· Stem cell transplantati
tion - use ofh
f very i
hi h
g dose
chemotherapy, requiring a stem cell rescue for bone
marrow recovery
· Radiation therapy - use of high-energy external beam
radiation to destroy cancer cells or stop them from
growing
· Treatments under clinical investigation
From International Myeloma Foundation. Multiple myeloma: Concise Review of the Disease and Treatment Options.
5
2006. IMF, North Hollywood, CA. www.myeloma.org
Why Are Some People Treated in
C?
Clinical Trials?
Your provider may recommend you participate in a
li
c
i
n
l
ca tri l
a . Cli
Clinical trials help fi
find new and safe
treatments. These trials are monitored by the FDA for
safety and effectiveness.
In order to participate in a clinical trial:
· Physicians follow specific instructions, which ensure excellent
care
· Patients are told all of the details of the study and willingly agree
to participate
· Patients need to meet specific eligibility criteria
· Patients can withdraw from a clinical trial at any time
6
Types of Trials
Dose-seeking trial to identify side
Phase 1
effects
Determine response rate for a
Phase 2
particular disease
Compare new treatment to standard
Phase 3
treatment
7
ClinicalTrials.gov Understanding Clinical Trials.
Use of Novel Agents for
Treatment of Multiple Myeloma
Thalidomide (Thalomid)
Lenalidomide (Revlimid
(Revlimid)
Bortezomib (Velcade)
Novel Agents
What is Targeted Therapy
Normal
Cells
Cancer
Cells
·Drugs
·
targeted at pathways, processes and physiology which are
are
uniquely disrupted in cancer cells:
Receptors
Genes
Angiogenesis
Tumor pH
·New agents improve
gp
outcomes either alone or combined with
chemotherapy and/or radiation
9
Novel Treatments for Multiple Myeloma -
Thalidomide and Lenalidomide
· These medications are called Immune-Modulating
therapies because they act to improve the
immune system
· Oral administration
· Strong evidence that these drugs kill cancer cells
in two ways
Improve body's immune system response to cancer
Block the blood supply to cancer cells, so that tumors
cannot grow
· Indications
Thalidomide: newly diagnosed and relapsed disease
Lenalidomide: combination with
with dexamethasone for patients
who have received at least one prior therapy
From Understanding Thalidomide. The International Myeloma Foundation, North Hollywood, CA. 2006
10
Potential Side Effects - Thalomid
(thalidomide)
()
· Blood clots, particularly in combination with steroids or
ht
chemo h
therapy
· Peripheral neuropathy numbness or tingling in your
hands or feet
· Sedation, fatigue
· Constipation
· Rash, usually on trunk, back, arms, legs
· Teratogenic - severe birth defects if taken during
pregnancy
11
Potential Side Effects - Revlimid
(lenalidomide)
· Blood clots, particularly in combination with steroids or
chemotherapy
· Low blood counts
· Rash
· Itchy scalp
yp
· Diarrhea
· Fatigue
· Muscle cramping
12
Novel Treatments for Multiple Myeloma
Velcade (bortezomib)
(bortezomib)
· Bortezomib is the first
first drug in a class
class called Proteasome
Inhibitors which inhibit cancer cell growth
· Normal cells can recover from effects of proteasome
inhibitor, whereas
whereas myeloma cells are more
more likely to
to be
be
effected
· Administered by intravenous injection (IV) several days
during a month
· Indications
Approved for use
use in previously untreated patients (June
(June, 2008)
Used to treat patients who have received at least 1 previous
therapy for multiple myeloma
San Miguel, J. F., et al NEJM; August, 2008
13
Potential Side Effects - Velcade
(bortezomib)
· Peripheral neuropathy numbness or tingling in your
hands or feet
· Low platelet counts
· Weakness and fatigue
· Loss of appetite, nausea, vomiting, diarrhea, or
consti ti
pa on
· Fever
· Joint pain, muscle cramps
· Shortness of breath, dizziness, blurred vision,
hypotension
14
Managing Side Effects of
Myeloma Treatment
Gastrointestinal
Ml
Myelosuppression
Thromboembolic
Peripheral Neuropathy
Steroids
Possible Side Effect of Treatment:
Gastrointestinal (GI)
GI side effects can happen individually or in
combination and commonly include:
· Nausea
· Vomiting
· Diarrhea
· Constipation
16
Possible Gastrointestinal Side Effect of
Treatment - Managing Nausea/Vomiting
Things that may help - Nausea and Vomiting
· Concentrate on staying hydrated
hydrated · Restrict fluids with meals
· Eat before getting too hungry
· Chew food thoroughly
· Eat bland food, cold or at room
· Suck on mints or hard candy;
temperature
popsicles or ice chips.
· Find fresh air when possible
· Try peppermint or ginger tea
· Use relaxation
relaxation techniques
techniques
· Apply a cool compress to the
· Try hypnosis or acupuncture
forehead, neck, wrists
Medications to control nausea may be ordered by your health care
provider. Take as directed.
17
Possible Gastrointestinal Side Effect of
Treatment - Managing Nausea and Vomiting
Vomiting
Things
g to avoid - Nausea and Vomiting
· Avoid strong odors
· Avoid favorite foods (they
· Do not lie flat after eating
may become associated
associated with
· Avoid sweet, salty, fatty,
nausea or vomiting)
spicy, heavy foods
· Avoid citrus and tomatoes
· Do not exercise after eating
If nausea and vomiting
vomiting continue
continue, your health care provider
provider
may add more anti-nausea medication and/or lower the
dose of treatment medication.
18
Possible Gastrointestinal Side Effect
fT
of Treat
t
men - Mi
Managing Di
Diarrhea
Medications that may cause diarrhea
· Laxatives
· Antibiotics
· Antacids with magnesium
· Antidepressants
· Prescription medications: check with your provider
Herbal supplements that may cause diarrhea
· Milk thistle
· Aloe
· Cayenne
· Saw palmetto
· Ginseng
19
Possible Gastrointestinal Side Effect
of Treatment - Managing Diarrhea
Et
Ea i
ting hi
hi t
n s for di
diarrhea
· Increase fluid intake (water, Ricelyte ®, Pedialyte®, sports
drinks, diluted fruit
fruit juice, and broth)
· Avoid caffeinated, carbonated, or heavily sugared beverages
Take anti-diarrheal medication
· Imodium® or Lomotil® if recommended by a clinician
· Fiber binding agents Metamucil®, Citracil®
20
Possible Gastrointestinal Side Effect
of Treatment - Managing Constipation
Eating hints for constipation
· Increase fluid intake
· Drink warm/hot beverage prior to normal timing for bowel
movement
· Eat foods high in fiber, for example....
Other techniques to manage constipation
· Ensure comfort, privacy, and convenience during bowel movement
· Increase physical activity
· Use stool
stool softeners or
or laxatives
laxatives or fiber binding agents
Metamucil®, Citracil®
Contact your provider if symptoms continue
continue. Your
Y
medications may need to be changed.
21
Possible Side Effect of Treatment:
Myelosuppression (low blood counts)
· The healthy bone marrow cells include:
Red Blood Cells (RBC) transport oxygen
White Blood Cells (WBC) fight against infection
Platelets protect against bleeding and bruising
· These cells can be effected by active disease, myeloma
treatment, and other
other medications or medical conditions.
· Decreased function of the bone marrow is called
"Myelosuppression"
· Your health care provider will monitor blood counts
regularly during therapy
22
Miceli, Colson, Gavino, Lilleby CJON Supplement, June, 2008. In press
Anemia (low red blood cells)
Commonly seen with myeloma. May also be a
result of decreased kidney function, myeloma
tt
treat
t
men or t
o h
ther
d
me i
di
t
ca i
tions.
Symptoms of anemia
Ft
Fa itigue, low energy l
l
eve
Unable to do regular activities
Shortness of breath or chest pain with activity
Pale appearance
Treatment
· Use of red bl
bl d
oo
ll
ce
l
supp
t
emen s, ith
w
t
cau ition
· Possible red blood cell transfusion
· "Energy-sparing" activities
· Reduced dose of
of medications
medications
23
Miceli, Colson, Gavino, Lilleby CJON Supplement, June, 2008. In press
Neutropenia (low white blood cells)
May be a result of myeloma disease, treatment or other
medications.
The greatest concern with this side effect is infection.
Symptoms to watch for
· Fever and shaking chills
· Dizziness or fainting
· Redness or swelling of skin or open wound
· Respiratory symptoms such
such as
as cough
cough or sinus congestion
Precautions
· Thorough hand washing to reduce contact exposure
· Use of mask as instructed
· Avoid crowds and potential contagion
· Preventative antibiotic therapy
therapy as prescribed
24
Miceli, Colson, Gavino, Lilleby CJON Supplement, June, 2008. In press
Thrombocytopenia (low platelets)
May be a result of myeloma disease, treatment or other
medications.
Wth
Watch for
t
symp oms tht
that may include
· Frequent or large bruises
· Blood in urine or stool
· Spontaneous nosebleeds
· Small red or purple spots on the body (petechiae)
· Bleeding that does not stop with pressure
To reduce risk of bleeding these practices are recommended:
· Do not take aspirin, ibuprofen or naproxen unless instructed
· Avoid activities that can cause bruising or bleeding such as contact
sports and heavy lifting
· May need platelet transfusion at signs of bruising or bleeding or
before any necessary invasive procedure
25
Miceli, Colson, Gavino, Lilleby CJON Supplement, June, 2008. In press
Possible Side Effect of Treatment: Deep
Vein Thrombosis and Pulmonary
Pulmonary Embolism
Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)
develop by
py a blood clot partiall
p
y or completel
p
y blocking a
blood vein or artery.
Risk factors for developing blood clots:
- Multiple myeloma
- Diabetes
- Recent surgery
- Immobility
- Obesity
-Smoking
- Family history of clots
- Current use of
of oral
oral contraceptives
contraceptives or hormones
- Cardiac problems
- Varicose veins
- Some combination treatments such as steroids
ith
w
th
th lid
a
id
om e or lenalid
lidomide
26
Possible Side Effect of Treatment:
Deep Vein Thrombosis and Pulmonary
Pulmonary Embolism
Symptoms of DVT
Symptoms of PE
·Sl
Swo l
llen, warm
i
extrem ty
· Shortness of b
h
reat , diffi
difficult
·Dull ache, pain or tight feeling
or labored breathing
·Rapid heart rate
· New onset of chest or
shl
hou d
lder bl
blade/arm pain
·Abnormal redness of skin
· Anxiety
·Bluish color and cool skin
· Rapid heart rate
Report DVT and PE sy
pymptoms
p
immediately
These events are considered a medical emergency
and require immediate care
27
Managing Side Effects of Treatment:
Deep Vein Thrombosis and Pulmonary
Pulmonary Embolism
Strategies to reduce risk of clots:
· Anti-em
e bo
b li
o sm stockings (elast
eastic stoc
stockings
gs)
· Exercise regimen
· Low-dose aspirin
· Moving frequently when sitting long periods
· Travel precautions (Foot/leg exercises, walking, ASA if not
already on blood thinner)
When taking Thalidomide or Lenalidomide, medications
may be adjusted to reduce the risk of a a clot from
occurring:
g
· Lower drug doses
· Different dosing schedule
· Blood thinning with warfarin or heparin therapy
28
Possible Side Effect of Treatment:
Peripheral Neuropathy
Peripheral Neuropathy develops by injury, inflammation,
or degeneration to the peripheral
peripheral nerve
nerve fibers of one's
extremities
Symptoms of peripheral neuropathy include:
· Numbness
· Tingling
· Prickling sensations
· Sensitivity to touch
· Muscle weakness
· Burning Pain or Cold Sensation
Report symptoms of peripheral neuropathy to
your health care provider early
29
What to Do in Case of Numbness or Pain
Due to
to Peripheral
Peripheral Neuropathy
If you experience numbness, tingling, freezing, throbbing or
shooting pain
pain due to peripheral neuropathy,
neuropathy, you might:
might:
· Massage the affected area with cocoa butter regularly
· Take B-complex vitamins (B1, B6, B12) supplements
· Take folic acid supplements
· Take amino acid supplements
If these symptoms worsen you should call your health care
provider, who may recommend:
· To stop treat
t
men or reduce the dose f
o Thalidomide,
Lenalidomide, or Bortezomib
· A pain medication like gabapentin or Lidoderm® patch
· Physical therapy
ypy
Proper management of PN will promote safety, increase
mobility, and prevent unnecessary pain and discomfort.
30
Steroid Therapy
Steroids are a very important part of the treatment for
multiple myeloma. Dexamethasone and prednisone are
ld
commonly used.
They have been used as a single drug or in
combination with other drugs for many
gy years.
y
Steroids target the myeloma cells for programmed cell
death.
- A recent study found benefit in using lower doses of
steroids over the conventional higher doses. Using
lower doses represented better overall survival and
less side effects. (Rajkumar, et al, 2007)
31
Potential Side Effects - Steroids:
Increase in blood sugar levels this can cause or worsen
diabetes
Fatigue/Hyp
gy eractivit
p
y
Difficulty sleeping (Insomnia)
Flushing/Sweating
Irritability, mood swings, depression
depression
Increased in risk of gastrointestinal complications including
stomach bloating, hiccups, heartburn, ulcers or gas.
Body image changes
changes - Weight gain, hair thinning/loss
thinning/loss, skin
rashes
Increase in blood pressure and water retention
Increased susceptibility to
f
in ections
Sexual dysfunction
Muscle weakness or muscle cramping
pg
Blurred vision
32
Managing Side Effects to Steroid Therapy
Things to consider while taking steroids:
Take with food
O
th
ver-
t
e-coun er or prescri ti
p on medications are
recommended to prevent stomach discomfort
Steroid schedule (am vs. pm
(p )
Medications to prevent shingles, thrush or other
infections may also be prescribed
Report signs
signs and symptoms of
of infection
infection (fever f
o more
than 100.5 ° F, shaking chills even without fever, dizziness,
shortness of breath, low blood pressure)
Do not stop or adjust steroid doses without
discussing it with your health care provider.
33
Let me hear from you
Questions & Comments
Comments
34