Understanding
TRISENOX®
(arsenic trioxide)Therapy
Table of Contents
Introduction
5
What Is TRISENOX®,
and How Does It Work?
6
Clinical Studies Show TRISENOX®
Is Active in Patients With Myeloma
8
What Is Next for TRISENOX®?11
What Are Some of the Possible
Side Effects of TRISENOX® Therapy?
12
Who Should Not Take TRISENOX®?14
How Is TRISENOX® Given?
15
What Questions Should I Ask
My Doctor About TRISENOX®?15
Where Can I Get More Information?
15
Will Insurance Cover the Cost
of TRISENOX® Therapy?
16
About the IMF
17
Glossary
20
Sponsored by an unrestricted educational grant from
Cell Therapeutics, Inc.
©2004, International Myeloma Foundation,
North Hollywood, California
Introduction
You have been given this booklet to learn more
about a new drug called TRISENOX® (arsenic
trioxide)*. After reading this booklet, you
should know:
What TRISENOX® is and how it works,
The possible side effects of TRISENOX®, and
What the basic types of TRISENOX®- based
treatment are and how they are given.
This booklet is meant to provide you with
general information only. It is not meant to
replace the advice of your doctor, nurse, or
pharmacist, who can answer questions related
to your specific treatment plan.
*Words appearing in italics are described in the glossary at
the back of the booklet.
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5
What Is TRISENOX®, and How Does
self-destruct by a natural biologic process called
It Work?
apoptosis. When activated, apoptosis pro-
grams cells (in this case, cancer cells) to destroy
TRISENOX® (arsenic trioxide) is a type of anti-
themselves. This promotion of apoptosis is the
cancer agent that is derived from arsenic, a
most direct and essential action for TRISENOX®
naturally occurring compound that has been
to inhibit the growth of cancer cells.
used for thousands of years in Chinese and
TRISENOX® may also prevent cancer cells
western medicine to treat a wide range of
from performing another biologic process
called
disorders. In the 1930s, naturally occurring
angiogenesis (the growth of new blood
vessels). As a result, cancer cells are unable
arsenic was found to be effective for treating a
to obtain nutrients for survival and growth
type of leukemia known as chronic myelogenous
from the bloodstream.
leukemia(CML). Recently, interest was renewed
TRISENOX® stimulates immune system "killer
in this agent as an anticancer agent when
cells" called LAK (lymphokine-activated killer)
researchers reported promising results in
and NK (natural killer) cells. Once activated,
patients receiving it for the treatment of acute
LAK and NK cells target cancer cells for
destruction.
promyelocytic leukemia (APL). In 2000,
TRISENOX® was approved by the FDA for the
TRISENOX® may also inhibit the growth of
cancer cells by inhibiting molecules that
treatment of APL, and researchers have contin-
promote cellular growth.
ued to explore the use of TRISENOX® in the
treatment of other cancers of the blood.
Laboratory and clinical trials continue to
Figure. TRISENOX® fights cancer cell growth in
investigate whether TRISENOX® is safe and
several ways.
effective in the treatment of other blood
TRISENOX®
disorders including myeloma.
Although the exact mechanism for how
TRISENOX® works continues to be explored, its
Stimulates
anticancer activity is believed to arise from
Promotes
Inhibits
Immune System
Apoptosis
Angiogenesis
multiple processes.
Killer Cells
TRISENOX® appears to cause cancer cells to
Cancer Cell Death
6
7
Clinical Studies Show TRISENOX® Is
that have been demonstrated to be tolerable
and active are listed below.
Active in Patients With Myeloma
Laboratory and Single-Agent Trials Show TRISENOX® Is
TRISENOX® With Ascorbic Acid (Vitamin C)
Active and Tolerable
The ability of TRISENOX® to destroy cancer cells
Although some people immediately consider
is enhanced when levels of a compound called
naturally occurring arsenic to be a toxic
glutathione are lowered in cancer cells. Because
substance, laboratory experiments and clinical
ascorbic acid (more commonly known as
trials have shown that TRISENOX® is a safe and
vitamin C) has this ability, researchers have
effective anticancer agent when used as recom-
performed laboratory experiments in myeloma
mended by physicians. Although some patients
cells and have conducted clinical trials to
have shown little or no response, some patients
evaluate whether giving patients TRISENOX®
treated solely with TRISENOX® in trials of single-
and ascorbic acid together would result in
agent therapy can experience a reduction in
improved outcomes in patients with myeloma.
tumor cell numbers.
The researchers concluded from both labora-
tory and clinical trials that ascorbic acid
TRISENOX® Is More Active When Given in Combination
decreases glutathione in myeloma cells and
With Other Drugs
may enhance the activity of TRISENOX® in
TRISENOX® has successfully and safely
patients with this disease.
demonstrated activity against cancer cells in
patients with myeloma when administered
alone. Researchers speculate that giving
TRISENOX® simultaneously with other drugs
could further improve patient outcomes. This is
a common strategy, called combination therapy,
which doctors often use to treat patients with
cancer. In clinical trials evaluating this possi-
bility, patients with myeloma who have been
given TRISENOX® in combination with one or
more agents have demonstrated an improved
response to treatment, often experiencing a
complete
or
near-complete
remission.
Additionally, when given to patients as part of
a combination regimen, TRISENOX® has
demonstrated safety and tolerability compa-
rable to TRISENOX® when given alone.
Specific TRISENOX® combination regimens
8
9
MAC Therapy: Melphalan With TRISENOX® and Ascorbic Acid
What Is Next for TRISENOX®?
Because laboratory experiments have shown
Research is ongoing to evaluate TRISENOX® for
that TRISENOX® sensitizes myeloma cells to the
the treatment of myeloma. Current and future
cytotoxic effects of an anticancer drug known
clinical trials will continue to focus on combining
as melphalan, a series of case studies has
TRISENOX® with other agents. The goal of these
evaluated the possibility of giving 10 patients
trials is to develop new treatment regimens that
ascorbic acid and melphalan with TRISENOX®
improve the response of patients to therapy,
(a combination known as MAC therapy).
maintaining or improving their quality and
Results have been encouraging, showing that
length of life.
the MAC regimen is active and very well toler-
In addition to being evaluated in myeloma,
ated, with no serious side effects reported. All
TRISENOX® continues to be investigated in
patients treated responded to therapy, and
other blood disorders, including several forms
6/10 (60%) patients remained disease free for
of leukemia, lymphoma, and myelodysplastic
a median of 42 weeks. The results from this trial
syndromes, as well as solid tumor cancers such
indicate that TRISENOX® can be combined with
as prostate cancer and melanoma.
other drugs to aid in the treatment of myeloma.
Based on these promising results, a clinical trial
is in development to evaluate the safety and
activity of MAC therapy in a much larger group
of patients with myeloma.
TAD Therapy: TRISENOX® With Ascorbic Acid and Dexamethasone
TRISENOX® has also been shown in labor-
atory studies to sensitize myeloma cells to
dexamethasone, a synthetic steroid often used
to treat leukemia, lymphoma, and several
other diseases. Based on this finding,
researchers investigated whether a combin-
ation of TRISENOX®, ascorbic acid, and
dexamethasone (known as TAD therapy) is a
possible therapeutic option for patients with
myeloma. Based on data obtained from 20
patients, the investigators concluded that TAD
therapy is a valid treatment regimen for
patients with myeloma that will be investigated
further in additional clinical trials.
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11
What Are Some of the Possible Side
Common side effects that may arise while
Effects of TRISENOX® Therapy?
receiving TRISENOX® include dizziness, light-
Generally, most of the side effects associated
headedness, and low blood pressure. Should
with TRISENOX® are manageable and pre-
these symptoms occur, the rate at which a
dictable. Doctors, nurses, and pharmacists can
patient receives his or her infusion of
provide more information in greater detail
TRISENOX® may be altered.
about these and other possible side effects.
Some patients receiving TRISENOX® experience
Side effects associated with TRISENOX®
QT prolongation, which means that the heart
therapy are unlike typical chemotherapy-related
takes a longer than usual time to relax in
side effects. TRISENOX® may therefore be less
between beats. In severe QT prolongation
likely to impact the patient's daily life compared
situations, fainting or other more serious side
with other cancer medications the patient
effects may occur. To monitor potential changes
may have previously received. For example,
in heart rhythm, the doctor may perform
few patients receiving TRISENOX® have experi-
electrocardiograms and test the patient's blood
enced hair loss or pain and inflammation of
more frequently. If blood tests indicate low
mucous membranes.
levels of magnesium or potassium, daily doses
of these electrolytes may be prescribed, since
adequate levels of magnesium and potassium
help prevent heart rhythm changes.
Other, less serious side effects that may occur
while receiving TRISENOX® include:
Skin problems or rash
Headache
Nausea
Fatigue
Bone and joint pain
Fluid retention
Constipation or diarrhea
Insomnia
In general, patients should consult a doctor or
health care professional if they experience any
of these or other less common side effects.
12
13
Who Should Not Take TRISENOX®?
How Is TRISENOX® Given?
Before administering TRISENOX®, doctors or
TRISENOX® is given intravenously over one
health care professionals should evaluate the
to two hours. If low blood pressure, light-
patient, including history of response to other
headedness, or dizziness occurs when
drugs used to treat myeloma.
TRISENOX® is first given, administration may
be slowed down and extended over a four-
The following subsets of patients should not take
hour period to alleviate these symptoms. In
TRISENOX®:
almost all cases, TRISENOX® can be given on
Patients with documented hypersensitivity to
an outpatient basis.
arsenic or who are intolerant of TRISENOX®
What Questions Should I Ask My
therapy should not take TRISENOX®.
Doctor About TRISENOX®?
Women who are pregnant should not take
Questions you may want to ask your doctor or
TRISENOX®. Laboratory studies indicate
health care professional before receiving
that TRISENOX® is potentially harmful to
TRISENOX® include:
developing fetuses.
How often and how long will I be taking
Because arsenic may be present in excreted
TRISENOX®?
human milk, women who are breast-feeding
are advised to discontinue either breast-feeding
What side effects may occur while I am
or TRISENOX® therapy.
receiving TRISENOX®?
Women of childbearing potential are advised
Is there anything I should avoid while taking
to avoid pregnancy while taking TRISENOX®.
TRISENOX®?
Will Taking Other Drugs or Medications Affect TRISENOX®?
Can you provide me with additional patient
Before taking TRISENOX®, the attending
education information about TRISENOX®?
physician or health care professional should
Where Can I Get More Information?
be notified of any other prescription or
over-the-counter medications, vitamins, diet
Your doctor or health care provider may have
supplements, or herbal products the patient
written
information
available
regarding
may be taking, as these or other compounds
TRISENOX®. Additional information can be
may interact or interfere with TRISENOX®
obtained by visiting the Cell Therapeutics, Inc.,
treatment. This is particularly important for
website at www.cticseattle.com or by contact-
patients taking heart medications or other
ing the company at 800-715-0944.
medications that may affect heartbeat, as
these drugs may adversely interact with
TRISENOX® and increase the risk of potentially
harmful irregular heartbeats.
14
15
Will Insurance Cover the Cost of
About the IMF
TRISENOX® Therapy?
"One person can make a difference.
Because TRISENOX® has been approved by the
Two can make a miracle."
FDA for relapsed/refractory APL, Medicare and
Brian D. Novis
most insurance programs are likely to provide
IMF Founder
reimbursement. Individual insurance coverage
may vary, however, so patients are advised to
Myeloma is a little-known, complex, and often
contact their individual insurance companies
misdiagnosed bone marrow cancer that attacks
regarding TRISENOX® coverage. To obtain
and destroys bone. Myeloma affects approxi-
additional information or should problems arise
mately 75,000 to 100,000 people in the United
with compensation, contact Cell Therapeutics,
States, with more than 14,500 new cases diag-
Inc., at 866-261-7730.
nosed each year. While there is presently no
known cure for myeloma, doctors have many
approaches to help myeloma patients live better
and longer.
The International Myeloma Foundation (IMF) was
founded in 1990 by Brian and Susie Novis shortly
after Brian's myeloma diagnosis at the age of 33.
It was Brian's dream that future patients would
have easy access to medical information and
emotional support throughout their battle with
myeloma. He established the IMF with the three
goals of treatment, 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 100,000. The IMF was the first
organization dedicated solely to myeloma, and
today it remains the largest.
The IMF provides programs and services to aid in the
research, diagnosis, treatment, and management of
myeloma. The IMF ensures that no one must brave
the myeloma battle alone. We care for patients
today, while working toward tomorrow's cure.
16
17
How Can the IMF Help You?
SUPPORT
MYELOMA HOTLINE: 800-452-CURE
PATIENT EDUCATION
Toll-free throughout the United States and
INFORMATION PACKAGE
Canada, the IMF Hotline is staffed by specialists
Our free IMF InfoPack provides comprehensive
trained by the National Cancer Institute (NCI).
information about myeloma, treatment options,
disease management, and IMF services.
SUPPORT GROUPS
It includes our acclaimed Patient Handbook.
A worldwide network of more than 100 myeloma
support groups hold regular meetings for
INTERNET ACCESS
members of the myeloma community. The IMF
Log on to www.myeloma.org for 24-hour
conducts annual retreats for myeloma support
access to information about myeloma, the IMF,
group leaders.
education, and support programs.
RESEARCH
ONLINE MYELOMA FORUM
Join the IMF Internet Discussion Group at
BANK ON A CURE®
www.myeloma.org/listserve.html to share your
This DNA bank will provide genetic data
thoughts and experiences.
research in new drug development.
MYELOMA MINUTE
THE INTERNATIONAL STAGING SYSTEM (ISS)
Subscribe to this free weekly email newsletter
This updated staging system for myeloma will
for up-to-the-minute information about myeloma.
enhance physicians' ability to select the most
appropriate treatment for each patient.
PATIENT & FAMILY SEMINARS
Meet with leading experts in myeloma treatment
RESEARCH GRANTS
to learn more about recent advances in therapy
Leading the world in collaborative research and
and research.
achieving extraordinary results, the IMF Grant
Program supports both junior and senior
MYELOMA MATRIX
researchers working on a broad spectrum of
New to our website and in print, this program
projects. The IMF has attracted many young
is a comprehensive guide to drugs in develop-
investigators into the field of myeloma, and they
ment for myeloma.
have remained in the field and are actively pur-
suing a cure for this disease.
MYELOMA TODAY NEWSLETTER
Our quarterly newsletter is available free of
charge by subscription.
18
19
Electrocardiogram: A test used to evaluate heart
Glossary
rhythm, in which electric conductors are placed on the
Acute promyelocytic leukemia (APL): A subtype of
body to produce an electrical reading of the heart's con-
the cancer known as acute myeloid leukemia (AML). APL
tractions.
is characterized by abnormal promyelocytes, a type of
Killer cell: A white blood cell that is part of the immune
white blood cell. When APL occurs, these abnormal
system and kills cancer cells. See lymphokine-activated
promyelocytes accumulate in the bone marrow and
killer (LAK) cell and natural killer (NK) cell.
peripheral blood and replace normal blood cells.
Lymphokine-activated killer (LAK) cell: A type of
Angiogenesis: The growth and formation of new blood
white blood killer cell that, when stimulated, destroys
vessels, often stimulated by cancer cells to obtain nutrients.
cancer cells.
APL: See acute promyelocytic leukemia (APL).
MAC therapy: A type of combination chemotherapy
Apoptosis: The programmed death of cells through
that treats myeloma patients with the drugs melphalan,
biologic processes. Although it occurs naturally and
TRISENOX®, and ascorbic acid.
normally in several biologic functions, apoptosis can be
Melphalan: An anticancer drug that belongs to a class
stimulated in tumor cells by certain cancer drugs.
of drugs called alkylating agents. Alkylating agents work
Ascorbic acid: The scientific name for vitamin C.
by damaging DNA and inducing the death of tumor cells.
Vitamin C/ascorbic acid is required for healthy teeth and
Myeloma: A type of cancer that appears in plasma
gums, helps in the absorption of iron, aids in the mainte-
cells, which are white blood cells that produce antibodies
nance of normal connective tissue, and promotes wound
to fight infection. Cancerous plasma cells are called
healing. It also is an antioxidant that contributes to a
myeloma cells. Myeloma cells damage bones and pre-
healthy immune system. In certain cases, ascorbic acid
vent the bone marrow from creating normal plasma cells,
may be given to patients taking TRISENOX® to improve
other white blood cells, and red blood cells. Also known
their response to TRISENOX® therapy.
as multiple myeloma.
Chemotherapy: The treatment of cancer by means of
Natural killer (NK) cell: A type of white blood cell
chemical substances and/or drugs.
that releases proteins capable of destroying cancer cells.
Chronic myelogenous leukemia (CML): A slowly
QT prolongation: An increase in the amount of time it
progressing blood disorder in which too many white
takes the heart to relax in between beats.
blood cells are made in the bone marrow, eventually
Single-agent therapy: A type of therapy where only
replacing normal white blood cells.
one drug is given to patients.
CML: See chronic myelogenous leukemia (CML).
TAD therapy: A type of combination chemotherapy
Combination therapy: Treatment that uses two or
that treats myeloma patients with the drugs TRISENOX®,
more drugs.
ascorbic acid, and dexamethasone.
Cytotoxic: An agent or process with the ability to kill cells.
TRISENOX® (arsenic trioxide): An anticancer drug
Dexamethasone: A synthetic steroid similar to steroid
that is used in the treatment of several types of leukemia
hormones produced naturally in the adrenal gland.
and other types of cancer. A derivative of naturally occur-
Dexamethasone is used to treat leukemia, lymphoma,
ring arsenic, TRISENOX® can reduce or eliminate cancer
and certain problems caused by other cancers and their
cells from patients through several mechanisms.
treatment.
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Appointments
Date
Time
Important Notes
International Myeloma Foundation
12650 Riverside Drive, Suite 206
North Hollywood, CA 91607 USA
Telephone:
800-452-CURE (United States and Canada)
818-487-7455
FAX:
818-487-7454
TheIMF@myeloma.org
www.myeloma.org
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