Doxorubicin: Weighing the Risks and Benefits

Doxorubicin: Weighing the Risks and Benefits

Alesandra Hlaing
Northeastern University

Doxorubicin: Weighing the Risks and Benefits

Abstract
Chemotherapy is a well-known treatment plan for cancer patients. Though it is
very popular, it is notorious for its strongly negative side effects both during and after
completion of the treatments. Each chemotherapy regimen can differ due to a variety of
factors that the patient can exhibit. It can be determined that in certain situations, a
chemotherapy regimen is not always the best choice for a patient. This article explores a
specific chemotherapeutic agent, Doxorubicin, and its negative effects on a patient. One
of the main negative effects of this drug is its cardiotoxicity, which can be a fatal side
effect of this drug. This article is meant to look into deeper detail of the risk factors of
patients interested in starting this regimen. By exploring the previous health conditions of
the patient prior to this treatment, it is possible to determine if the therapy will be a good
fit for the patient.

Doxorubicin: Weighing the Risks and Benefits

Introduction
Cancer is a prominently widespread illness involving the abnormal and
uncontrolled growth of mutated cells in the body. Cancer takes the lives of roughly 1,600
people each day, with new types of cancers appearing rapidly. With the growing numbers
of types of cancers and people affected by cancer, it is hard to fathom how many people
have dedicated their lives to researching new ways to combat cancers. A commonly
associated area of study that usually shortly follows the mention of cancer is the topic of
chemotherapy. Chemotherapy is a treatment regimen for cancer patients that usually
involves anticancer drugs that are used to destroy the abnormal cells. However,
chemotherapy, though effective, is a largely questionable practice due to the multitude of
negative side effects that occur both during treatment, and even on a long-term basis after
termination of treatment. One of the most commonly used treatments in cancer is
doxorubicin, also known as Adriamycin, which is usually used with a variety of other
anticancer drugs. Doxorubicin has a variety of negative side effects that often make it
notorious in oncology. The main controversy revolving around doxorubicin is the
cardiotoxic effect that it places on the body both during and after the treatment.
Mechanism of Doxorubicin
Doxorubicin is officially classed as an anti-neoplastic agent as well as an
antitumor antibiotic. Doxorubicin is given intravenously, as this is the best method for
rapid administration into the body (Doxorubicin WEBMD). The main purpose of
doxorubicin is to combat cancer by slowing down or stopping the growth of cancer cells
in the body (Doxorubicin WEBMD). It is most one of the commonly used
chemotherapeutic agents because it can work on a variety of different types of cancers

Doxorubicin: Weighing the Risks and Benefits

like leukemia, lymphoma, breast cancer, ovarian cancer, and bone cancer. It is often used
in a combination of drug treatments referred to as ACT(Dunn 2014). ACT, which
stands for adriamycin, cytoxin, and taxotere, uses a combination of chemotherapeutic
agents that are administered over a three to four hour period totaling around eight or nine
administrations total. (Dunn 2014). However, it is important to understand that this is a
general overview of the treatment, and each individual patient will be administered a
variety of different doses of each anticancer drug, and some treatments may last longer
than others.
Doxorubicin belongs to a class of drugs known as Anthracyclines, derived from
the Streptomyces bacterium. When doxorubicin was first released, there was controversy
due to the conclusion that in killing the cancer cells, the drug would also kill some
healthy cells in the process. This is a common concern amongst most chemotherapeutic
agents, and plays a big factor in understanding the necessity for dosing strategies to
combat mostly the cancer cells in the body. There has also been an argument in the field
trying to discover the exact mechanism of Doxorubicin(Patel 2014). Though it is used for
a variety of cancers, the direct method of action for this drug is still relatively unknown.
A current popular proposal made by scientists at the University of Texas Southwestern is
that doxorubicin combats tumors through a method called regulated intramembrane
proteolysis (Patel 2014). The idea of this method is that doxorubicin cleaves a
membrane protein that allows particles to enter the cell and facilitate cell death (Patel
2014). Another method that is regarded is the idea that doxorubicin directly interacts with
DNA in a cell and inhibits topoisomerase II. Topoisomerase II is directly involved in
DNA transcription and replication, therefore disrupting this enzyme would cause a cell to

Doxorubicin: Weighing the Risks and Benefits

be unable to divide and spread (Patel 2014). The mechanism of action of Doxorubicin is
necessary in understanding why certain negative effects occur with this treatment.
Risks
Doxorubicin has gained a reputation as being referred to as the red devil or red
death chemotherapy among patients because of the negative side effects that occur
during treatment. Like most chemotherapeutic agents, the most common side effects
associated with doxorubicin occur in various parts of the body. The white blood cell
count in the body decreases, often leading to necessary surgery to replace bone marrow
(Doxorubicin WEBMD). There are major changes in the patients diet, as nausea,
vomiting, and a loss of appetite is common. A major side effect of chemotherapy is the
loss of hair, also known as alopecia, which is almost always expected and associated with
this type of treatment. With doxorubicin in particular, mouth sores and a sore throat are
very common. Though its most notable side effect is its cardiotoxicity, it is necessary to
note that there is also a significant effect that takes place in the arteries, which increases
the chances for clotting in the body (Uhm 2014). Another important factor that occurs
during administration is the major dermatological effects on the body that occurs due to
the chemotherapeutic agents. In a study conducted by Springer, it was determined that
undesirable dermatological effects occur in women after treatment of a variety of cancers
due to chemotherapeutic agents (Hackburth 2008). This is relevant because many studies
simply focus on hematologic toxicology of chemotherapeutic drugs, and not on
dermatological effects. The study showed that changes in the nail buds, as well as
fingertips were a prevalent commonality. Almost half of the patients tested in this study

Doxorubicin: Weighing the Risks and Benefits

also attested to the effects saying that it was the most unpleasant of side effects
(Hackburth 2008).
One of the most notably associated side effects with doxorubicin is the
cardiotoxicity that occurs both during and after administration. This occurs due to the
production of free radicals in the body after administering this drug(Patel 2012). There
are a variety of types of this toxicity that can be observed. One of the first cardiotoxic
effects that can occur is during administration. After a single dose of this
chemotherapeutic agent, arrhythmias, which are irregular heartbeats, can occur
(Chlebowski 1979). However, arrhythmias that occur due to doxorubicin are rarely fatal
and rarely need any drug treatment unless onset of arrhythmia appears to be a risk factor
in the patient (Bressler 1997). Both myocarditis and pericarditis have been known to
occur in patients taking doxorubicin. Myocarditis and Pericarditis are inflammations of
the myocardium and pericardium respectively, and can either be early symptoms or have
a delayed onset (Doxorubicin Cancer Care Ontario). A long-term effect that can occur
due to the use of this treatment is thromboembolism, which usually only occurs later after
administration. Thromboembolism is the formation of blood clots. This is a precursor to
congestive heart failure, one of the most disputed and recognized cardiotoxic effects that
doxorubicin can have on the body.
Congestive heart failure is another largely researched effect of doxorubicin use.
Though there are many factors that are involved with this type of effect, it has been noted
that upon first release of this drug, congestive heart failure occurred in half of patients
that the therapy was administered to (Chlebowski 1979). This effect is most common
after administration of the last dose of the drug, after a small period of time of no dose,

Doxorubicin: Weighing the Risks and Benefits

which is estimated to be around one to two months afterwards (Chlebowski 1979).

Congestive heart failure can occur due to doxorubicin administration but it is mostly
determined by the dose. The maximum cumulative life dose of the clinical use of
doxorubicin is 550 mg/m^2. This is because at 560 mg/m^2, the probability of a patient
developing chronic cardiomyopathy, which is permanent damage to the heart and can
lead to heart failure, is at thirty percent (Bressler 1997). There are many risk factors
associated with the cardiotoxic effect of heart failure, and therefore patients should be
examined on an individual basis to determine what risk factors the patient has before
starting this regimen.
Combatting the Risks
It is important to note that not all patients who undergo treatments with
doxorubicin and other drugs on the ACT treatment plan will have all side effects
associated with these drugs. Some patients are more at risk than other patients for the
cardiotoxic effects that occur. Patients who already had heart complications before
beginning treatments are more at risk to have heart failure during or after the treatment
(Chlebowski 1979). As already stated, the dose plays a major role in the cardiotoxicity of
doxorubicin. Another important risk factor when looking at doxorubicin negativity is age.
Younger-aged patients who begin a doxorubicin-based chemotherapeutic regimen are
more at-risk for cardiotoxic effect (Lipshultz 2014). Women are also at a higher risk for
congestive heart failure due to the weakening of the heart muscle (Lipshultz 2014).
Patients with obesity or dietary problems after treatment are also put at a higher risk for
heart problems with this drug (Lipshultz 2014). Patients who have had previous
experience with radiation therapies are also at risk, or those who are much later in age

Doxorubicin: Weighing the Risks and Benefits

that begin the treatment(Chlebowski 1979). Though there are many risk factors
associated with this drug, it is not possible to directly determine to what extent there will
be a cardiotoxic effect until administration begins, despite not having any common risk
factors associated with the patient.
There are many ways to combat the cardiotoxic effects of doxorubicin. The most
obvious mechanism for stopping the cardiotoxic effects is to control the doses given of
the drug. By determining the least necessary dose of the drug needed to have a anticancer
effect on the patient, it is possible to lower the dose enough to avoid the 550 mg/m^2
biomarker for cardiotoxicity. Since doxorubicins main mechanism for causing
cardiotoxicity is its production of free radicals in the body, drugs such as Dexrazoxane
can be used to block the formation of these free radicals in the body by creating
complexes between the doxorubicin and iron, which would reduce the number of free
radicals in the body (Bressler 1997). Another way to allow doxorubicin to have
significant effect on the body but minimal cardiotoxicity is to change the schedule that
the drug is administered during (Chlebowski 1979). By choosing to have this drug
administered on a weekly basis rather than having a longer period of time in between
administration has been shown cause a decrease in risk of cardiotoxicity (Chlebowski
1979). Overall, health care professionals have continued to make substantial changes in
learning more about the ways cardiotoxicity can be decreased in doxorubicin.
Doxorubicin continues to be both a highly beneficial anticancer drug that also has
many negative side effects associated with it. Though the short term and long-term
effects of this drug can be overwhelming in patients, there are many ways to combat
these issues in order to successfully remove the cancer from a patient. It is important that

Doxorubicin: Weighing the Risks and Benefits

health care providers let patients know the risks that are associated with doxorubicin
before administration in order to bring to light any risk factors that the patient may be
associated with before starting treatment. With the right amount of alteration in cancer
treatment, certain toxicities in the body can be avoided. Overall, doxorubicin serves to be
a beneficial drug that will continue to have detrimental side effects. It is important to
understand that the risks and benefits of a cancer regimen will differ from patient to
patient. The risks of taking such a harsh treatment plan should always be thoroughly
examined by a patient before they begin their therapy regimen.

Doxorubicin: Weighing the Risks and Benefits

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Works Cited

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CHEMOTHERAPY-INDUCED CARDIAC TOXICITY. The University of Illinois,
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<http://www.webmd.com/cancer/doxorubicin>.

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Dunn, Debbie. "How To Go Through First Red Devil Chemo Session." The Examiner, 18
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Personal Reflection:
I decided to refine my topic to focus on a specific chemotherapeutic agent and its
effects. I think that this paper will be a good piece to include in my portfolio. I
believe that though it is hard to write a truly scholarly paper on chemotherapy
due to complexity of the topic, I learned a lot about researching a topic in a
scholarly-based way. I believe that my research manifests itself as an
understandable and interesting topic to read about.