Understanding
Doxil®
in Myeloma
International Myeloma Foundation
12650 Riverside Drive, Suite 206
North Hol ywood, CA 91607 USA
Telephone:
800-452-CURE (2873)
(USA & Canada)
818-487-7455
Fax: 818-487-7454
TheIMF@myeloma.org
www.myeloma.org
2/08
Table of Contents
Introduction
5
What Is Multiple Myeloma?
5
What Are the Stages of Multiple Myeloma?
7
What Is Doxil® and How Does it Work?
8
What Are the Possible Side Effects of Doxil®
with VElcADE®?
9
can Doses of Doxil® or VElcADE® Be Reduced
If Necessary?
15
How Is Doxil® Plus VElcADE® Given?
15
Questions to Ask Your Healthcare Provider
15
About the IMF
17
Glossary
20
References
22
©2008, International Myeloma Foundation, North Hollywood, California
Introduction
You have been given this booklet to learn
more about a new drug called Doxil® (doxo-
rubicin HCl liposome injection). After read-
ing this booklet you should know:
n What Doxil® is
n How Doxil® works
n The possible side effects of Doxil®
n Why Doxil® is administered in combina-
tion with VELCADE®
n The possible side effects of Doxil® given in
combination with VELCADE® (bortezomib)
for injection
n How Doxil® Plus VELCADE® is given
This booklet is meant to provide you with
general information only. This booklet does
not take the place of discussions with your
doctor or nurse. Your doctor or nurse can
answer questions related to your specific
treatment plan. All words that appear in bold
type are defined in the glossary at the end
of the booklet.
What Is Multiple Myeloma?1,2
Multiple myeloma (also known as myeloma
and as plasma cell neoplasm) is a malig-
nancy of the immunoglobulin- (antibody)
producing plasma cells found in the bone
marrow. It is a hematologic malignancy
resembling leukemia. However, the malig-
nant plasma cel s, or myeloma cel s, rarely
enter the bloodstream as in a true leukemia.
4
5
Instead, the myeloma cells accumulate in the
The Stages of Multiple Myeloma2,3
bone marrow, causing:
Stage I (low cell mass): Early disease.
n Disruption of normal bone marrow func-
The bone structure appears normal or close
tion, most commonly giving rise to anemia
to normal on x-ray images; the number of
(a low level of red blood cells in the blood-
red blood cells and amount of calcium in the
stream), although reduction in white blood
blood are normal or close to normal, and the
cell and platelet counts can also occur
amount of M protein is very low.
n Damage to bone surrounding accumulated
Stage II (intermediate cell mass): An
myeloma cells
intermediate stage between stage I and III
n Release of an abnormal protein, mono-
clonal protein (M protein), into the blood-
Stage III (high cell mass): More
stream
advanced disease. One or more of the
following are present:
n Suppression of normal immune function,
observed as reduced levels of normal
n Anemia
immunoglobulins and increased suscepti-
n A high level of calcium in the blood
bility to infection
n More than 3 areas of advanced lytic bone
Myeloma cells can also grow in the form
lesions
of localized tumors or plasmacytomas.
n A high level of M protein in the blood or
Plasmacytomas may be single or multiple
urine
and either medullary (confined within bone
Multiple myeloma is a serious malignancy,
marrow and bone) or extramedullary (out-
but it is treatable. Many patients experience
side of the bone). When there are multiple
a series of responses, relapses, and remis-
plasmacytomas inside or outside bone, this
sions. With new treatments, the average sur-
condition is also called multiple myeloma.
vival of 5 years for patients diagnosed with
multiple myeloma may be extended.1
Following diagnosis, several options are
available for initial or frontline therapy.
For patients who may be candidates for
high-dose therapy with transplant, var-
ious induction regimens can be consid-
ered, including Thalomid® (thalidomide)
with dexamethasone,4 dexamethasone
alone, or other dexamethasone-containing
6
7
combinations.2 The combination of the alky-
lating agent melphalan plus prednisone,
a simple oral therapy, is an option for
patients not considering bone marrow (stem
cell) transplant with intravenous high-dose
melphalan.2 At the time of relapse, newer
agents are frequently required to achieve
further response. Revlimid® (lenalidomide) is
available for use in this setting.2,5 VELCADE®
(bortezomib) is also available for relapsed
myeloma.2,6 VELCADE® is discussed in a
separate booklet, Understanding VELCADE®,
which is available from the International
Myeloma Foundation.7 Doxil® given in com-
multiple myeloma who have not previously
bination with VELCADE® is an important new
received VELCADE® (bortezomib) and have
treatment option available.
received at least one prior therapy.8
A large clinical phase III study looked at the
What Is Doxil® and How Does it
safety and efficacy of Doxil® in combina-
Work?
tion with VELCADE® in 646 patients with
myeloma who had not previously received
Doxil® is a prescription medication given to
VELCADE® and whose disease had pro-
you by your doctor. Doxil® is a different form
gressed during or after at least one prior
of the chemotherapy agent doxorubicin.
therapy. Patients were randomly assigned to
Doxil® is made by coating doxorubicin with
receive either Doxil® plus VELCADE® (324
lipid (fat). The fat bubble containing doxoru-
patients) or VELCADE® alone (322 patients).
bicin is called a liposome. The liposome is
The median time to disease progression for
surrounded by another layer of a rubber-like
patients treated with Doxil® plus VELCADE®
material cal ed methoxypolyethylene glycol
was 9.3 months compared with 6.5 months
(MPEG). This textured MPEG layer around
for patients treated with VELCADE® alone.8
the liposome may increase the time that
Doxil® circulates in the bloodstream by
What Are the Possible Side Effects
protecting it from detection and destruction
of Doxil® with VELCADE®?8
by the immune system. The FDA has recent-
ly approved Doxil® in combination with
This is not a complete list of side effects. Talk
VELCADE® (bortezomib) to treat patients with
to your doctor or nurse for more information,
8
9
or if you experience these or any other side
slowing or stopping the infusion. In some
effects.
patients, these reactions may be serious of
life-threatening. If a reaction occurs, it usual y
Important Safety Information
happens during the first infusion.
You should not take Doxil® if you are nurs-
ing. If you are pregnant or are planning to
Let your doctor or nurse know if you experi-
become pregnant, inform your doctor.
ence any of these or other symptoms during
your infusion.
Heart-related Side Effects Cardiotoxicity
n Flushed feeling
Symptoms of heart-related side ef ects may
n
include the following:
Dizziness or light-headedness
n Shortness of breath
n Irregular heartbeat
n Chills
n Shortness of breath
n Back pain
n Fatigue
n Facial swel ing
n Ankle-swel ing, which is caused by excess
n Tightness in the chest or throat
fluid
n Headache
In some cases, these heart-related side ef ects
may be serious and possibly permanent.
Decreased Blood Cel Counts
Serious and possibly permanent heart-relat-
You may experience significant reduction in
ed side effects which may lead to congestive
the number of blood cells in your body. This
heart failure.
can cause other unwanted ef ects. Decreased
white blood cell counts (neutropenia) can
Your doctor will monitor your heart function
lead to fever and infections. Decreased red
and closely watch the dosage of Doxil® and
blood cell counts (anemia) can make you feel
any related chemotherapy agents. Inform
tired and fatigued. Decreased platelet counts
your doctor of any history of heart disease,
(thrombocytopenia) can lead to impaired
radiation to your chest, or prior chemo-
blood clot ing and prolonged bleeding. Your
therapy. Notify your doctor or nurse imme-
doctor wil check al of your blood cel counts
diately if you experience any of the above
regularly, and may give you medication that
symptoms.
may help increase blood cel counts. Your
Infusion-related Reactions
doctor may also manage your blood cel
Infusion-related reactions have been seen in
counts by delaying and/or reducing your
some patients treated with Doxil®, so you
Doxil® and VELCADE® doses.
wil be closely observed for reactions during
Notify your doctor or nurse immediately
your infusion. In some patients, infusion-
if you develop a fever of 100.5°F or higher.
related reactions can be managed by either
10
11
Skin-related Reactions
You may experience a skin reaction cal ed
hand-foot syndrome (HFS), also called pal-
mar-plantar erythrodysesthesia (PPE). It usu-
al y occurs on the palms of the hands and
soles of the feet. HFS is generally observed
after 2 or 3 cycles of treatment, but may
occur earlier, Skin-related reactions may
also occur on other parts of the body where
your clothes may be tight or where friction,
pressure, rubbing, warmth, and/or sweating
occur.
Another skin-related reaction is stomatitis, a
mouth irritation characterized by inflamma-
In most patients, the reaction is mild and
tion or sores.
improves in 1 to 2 weeks without a delay
in Doxil® therapy. However, in some cases,
Hand-Foot Syndrome (HFS)
hand-foot syndrome can be serious and
You or a friend or family member should
may impact your daily activities, which may
check regularly for signs of skin irritation
require either delaying or stopping Doxil®
and hand-foot syndrome. If you already have
therapy.
peripheral neuropathy (numbness or tingling
Stomatitis
in the hands and feet). If you already have
peripheral neuropathy, you may not feel the
Stomatitis may be managed with proper
symptoms of HFS.
care of your mouth and by avoiding certain
foods and beverages. Your doctor or nurse
Notify your doctor or nurse if you experi-
can provide you with guidelines that may
ence any of the following common signs and
symptoms of HFS:
help control stomatitis. For example, you
might be told to rinse your mouth daily with
n Redness
salt water.
n Rash
Notify your doctor or nurse if you experi-
n Pain or tenderness
ence any of the following:
n Swelling
n Mouth sores
n Tingling, burning, or itching
n Dry, swollen tongue
n Flaking or peeling of the skin
n Dry, cracked lips
n Smal blisters or smal sores on the palms
n Pain or burning in the mouth
of hands or soles of feet
12
13
n Inability to eat or drink
Can Doses of Doxil® or VELCADE®
n Difficulty swallowing
Be Reduced If Necessary?
Talk to your healthcare provider for sug-
Possible dose reductions of your medication(s)
gestions that may help manage hand-foot
are decisions best made by your physician.
syndrome or stomatitis.
Therefore, it is important to communicate
Nausea and Vomiting
openly with your doctor or healthcare pro-
Nausea and vomiting are usual y mild and
fessional and keep regular appointments to
may be managed with medication. Notify
maintain your treatment schedule. Your doc-
your doctor or nurse if you experience either
tor may choose to modify your dose of either
of these symptoms.
Doxil® or VELCADE® or both drugs as part of
Fluid Discoloration
an overall plan to manage a particular side
Because of its color, Doxil® may cause urine
effect that you experience.8
and other body fluids to turn reddish-orange.
This side effect is nontoxic and will disap-
How is Doxil® Plus VELCADE®
pear as Doxil® is eliminated from the body.
Given?
Other Most Common Side Effects
Notify your doctor or nurse if you experience
Both Doxil® and VELCADE® are given as
any of the following:
intravenous (I.V.) infusions, and must be
n
administered by a healthcare professional in
Nausea
a supervised environment, such as a doctor's
n Vomiting
office or clinic. VELCADE® is administered
n Tiredness
on days 1, 4, 8, and 11 of a 21-day cycle.
n Weakness
Doxil® is administered on day 4 only of the
VELCADE® schedule, and is given after the
VELCADE® dose.8
[Doxil Prescribing Information Section 2.4]
Questions to Ask Your Healthcare
Provider9
n How can I prepare for my treatment?
n Why do you recommend Doxil® plus
VELCADE®
14
15
n Wil my treatment keep me from doing
About the IMF
certain things?
n Will I be able to work and exercise
"One person can make a dif erence,
during treatment?
Two can make a miracle."
n How often wil I need to be checked
Brian D. Novis
IMF Founder
after my treatment?
n Can I go back to my normal daily
Myeloma is a lit le-known, complex, and
activities after treatment?
often misdiagnosed bone marrow cancer
that at acks and destroys bone. Myeloma
n What can I do to manage side effects?
af ects approximately 75,000 to 100,000
n Can I talk to any of your patients who
people in the United States, with more than
are currently receiving this treatment?
20,000 new cases diagnosed each year
n What other drugs or treatments might
according to recent data. While there is
I have to take?
presently no known cure for myeloma, doc-
n What symptoms or problems should
tors have many approaches to help myeloma
I report right away?
patients live better and longer.
The International Myeloma Foundation (IMF)
IMF Hotline:
was founded in 1990 by Brian and Susie
USA & Canada only: 800-452-CURE (2873)
Novis shortly after Brian's myeloma diagno-
Elsewhere: 818-487-7455
sis at the age of 33. It was Brian's dream that
IMF Web site: www.myeloma.org
future patients would have easy access to
medical information and emotional support
throughout their battle with myeloma. He
established the IMF with the 3 goals of treat-
ment, education, and research. He sought
to provide a broad spectrum of services for
patients, their families, friends, and health
care providers. Although Brian died 4 years
after his initial diagnosis, his dream didn't.
Today the IMF reaches out to an international
membership of more than 165,000. The IMF
was the first organization dedicated solely to
myeloma, and today it remains the largest.
16
17
The IMF provides programs and services to
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Log on to www.myeloma.org for 24-hour
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On our website and in print, this document is a
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comprehensive guide to drugs in development
for myeloma.
18
19
Glossary9,10
Alkylating agent: A chemotherapy agent that prevents the
Multiple myeloma: A cancer arising from the plasma cel s
growth and division of new cancer cel s by inhibiting their
in the bone marrow. The plasma cells in patients with
ability to replicate DNA.
multiple myeloma form abnormal antibodies, possibly
damaging the bone, bone marrow, and other organs.
Alopecia: Hair loss.
Neoplasm: Cancer.
Anemia: A low level of red blood cells in the blood-
stream.
Neutropenia: A low level of white blood cells in the
bloodstream.
Antibody: A protein produced by some of the body's white
blood cells that helps fight infection.
Peripheral neuropathy: Numbness, tingling, and/or pain in
the hands, feet, legs, and/or arms.
Bone marrow: A soft, spongy tissue found in most large
bones that produces red and white blood cel s and
Plasma cell: A type of white blood cel that produces
platelets.
antibodies.
Cardiotoxicity: Side effects affecting the heart.
Plasmacytoma: A tumor made up of cancerous plasma
cells.
Chemotherapy: Use of chemicals to treat or control cancer.
Platelet: An element in the blood that helps with clotting,
Congestive heart failure: Also known as heart failure; a
which in turn helps repair damaged blood vessels.
condition in which the heart is unable to pump blood to
the body's organs effectively.
Pulmonary embolism (PE): A blood clot that circulates in the
bloodstream and ends up in the lungs.
Deep vein thrombosis (DVT): A blood clot in the deep veins
of the lower part of the body
Red blood cell: A blood cell that carries oxygen from the
lungs throughout the body.
Hand-foot syndrome (HFS) or palmar-plantar erythrodysesthe-
sia (PPE): a skin irritation typical y occurring on the palms
Side effect: An effect caused by treatment with a drug. The
of the hands and soles of the feet or other parts of the
term usually refers to an unwanted effect, but some side
body where friction, rubbing, or sweating occurs.
effects may be beneficial.
Immune system: The system of white blood cel s and their
Stage I (low cell mass): Early myeloma disease.
products that helps the body resist infection and some
Stage II (intermediate cell mass): Stage of myeloma disease
cancers.
intermediate between stages I and III.
Immunoglobulin: An antibody.
Stage III (high cell mass): More advanced myeloma
Intravenous (I.V.) infusion: Delivery of a drug or fluid into
disease.
the body using a needle inserted into a vein.
Stomatitis: Mouth discomfort, including inflammation or
Lipid: Fat.
sores in the mouth.
Liposome: Fat bubble containing a drug or other sub-
Thrombocytopenia: A low level of platelets in the blood.
stance.
These low levels can cause bruising or bleeding as wel
as delay in the injury healing process.
Lysis (lytic): Dissolution or destruction of cells.
Time to disease progression: The length of time from the
Median: In the middle; the middle value of a series of
beginning of treatment until the disease begins to get
values in order from lowest to highest.
worse.
Monoclonal protein (M protein): An abnormal protein
White blood cell: A cel made by the bone marrow that
produced by myeloma cel s that accumulates in and
helps fight infection and/or disease.
damages bone and bone marrow. A high level of M
protein indicates that myeloma cells are present in large
numbers.
20
21
References
1. Kyle RA, Rajkumar SV. Multiple myeloma.
New Engl J Med 351:1860-1873
2. Durie BGM, Kyle RA, Belch A, et al. Myeloma
management guidelines: a consensus report from
the Scientific Advisors of the International Myeloma
Foundation. The Hematology Journal 4:379-398,
2003
3. Durie BGM, Salmon SE. A clinical staging system for
multiple myeloma. Correlation of measured myeloma
cell mass with presenting clinical features, response to
treatment, and survival. Cancer 36:842-854, 1975
4. Thalomid® (thalidomide) Prescribing Information,
Celgene Corporation, 2006
5. Revlimid® (lenalidomide) Prescribing Information,
Celgene Corporation, Thompson PDR, 2007
6. Velcade (bortezomib) for Injection® Prescribing
Information, Millennium Pharmaceuticals, 2006
7. Understanding Velcade (bortezomib) for Injection;
International Myeloma Foundation, 2006
8. Doxil (doxorubicin HCl liposome injection)
for intravenous infusion Prescribing Information,
Ortho Biotech, May 2007
9. Questions and Answers About Doxil; Ortho Biotech,
2007
10. Stedman's Medical Dictionary, 26th Ed. 1995
22