Chemotherapy and Biotherapy

Hypersensitivity Reactions

Christine E. Coyle, RN, BSN, OCN

Alverno College MSN Student
Spring 2011
[email protected]
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All images are from Microsoft Clipart, 2007.

 Learner Outcomes
At the end of this presentation the
learner will:
• Identify factors that place a patient at risk for
hypersensitivity reactions from cancer therapies,
such as chemotherapy and biotherapy.
• Review pathophysiology of hypersensitivity
reactions, including allergic, anaphylaxis, and
cytokine-release syndrome.
• Discuss the management of hypersensitivity
reactions, emphasizing the oncology nurse’s role.
 Clinical Significance
• Almost all cancer therapy infusions have been
reported to cause HSR’s.
• These reactions can be life-threatening and
requires that nurses are prepared to manage
them.
• Encourages the nurse to consider his/her role
in preventing reactions.
 Hypersensitivity Reaction
(HSR)
An over expressed immune response that
results in tissue harm or changes throughout
the body in response to an antigen or foreign
substance.
This can include an allergic reaction,
anaphylactic reaction or Cytokine-Release
Syndrome.
 Reactions…what’s the
difference?
• Allergic Reaction:
An unpleasant response from exposure to an allergen.

• Anaphylaxis Reaction:
An acute inflammatory reaction which results from the release of
histamine from mast cells, causing a hypersensitivity immune
response. It can presents with shortness of breath (SOB),
lightheadedness, hypotension, and loss of consciousness and can
lead to death.

• Cytokine-release syndrome :
Caused by the release of cytokines- can cause nausea, headache,
tachycardia, hypotension, rash, and SOB. It only occurs with
Monoclonal Antibodies.
National Cancer Institute, 2010
Click on a topic
Immune
Response
Genetics

Risk Factors for

Hypersensitivity
Reactions

Case Study Management

and Nurse Role

Cytokine-
release
syndrome
Reactions References
and Stress
 Risk Factors
• Type of Chemotherapy/Biotherapy Agent
• Previous History with the agent
• Allergies
• Age
• Genetics
 Incidence of Reactions
Agent Overall Grade 3-4
Carboplatin 2% none
(Paraplatin®)
Cetuximab (Erbitux®) 15-20%, dependent on 3%
tumor type

Docetaxel (Taxotere®) 5-12% 2%

Eloxatin (Oxaliplatin®) 15-33% 2-3%

Paclitaxel (Taxol®) 41% 2%
Rituximab (Rituxan®) 77% First infusion, 30% 10%
fourth infusion, 14%
eighth infusion

Vogel, 2010
 Time out…let’s reflect

Of the drugs previously mentioned, which one

has the highest incidence of HSR’s with the
first infusion?

Correct! Rituxan Incorrect

Paclitaxel

Incorrect Cetuximab Incorrect Paraplatin

 Review Patient’s History
Allergies
Assess your patient for • Food
previous reactions and/or • Drugs
allergies. • Insect stings
• Latex
• Vaccines
Know your patient’s health • Anesthesia Medications
history.
Other
Prior history of HSR’s increases • Female gender
risk to subsequent HSR’s ! • Cardiac, liver, kidney or
pulmonary dysfunction
• Older Age
• Asthma diagnosis

Gobel, 2005
 Time out…let’s reflect!
Which is an example of a drug where previous
and/or multiple exposure increases the risk for
reaction?
Incorrect Incorrect
Docetaxel Rituximab

Incorrect Paclitaxel Correct! Eloxatin

 Is the patient getting Rituximab
for the first time?
CHECK YOUR PATIENT’S LYMPHOCYTE COUNT!
Elevated Lymphocyte count (>40%) =
Increased risk for a reaction
Check your protocol!
 Drug Metabolism and Genetics
• Primary site of drug metabolism is the liver
• Cytochrome P450 (CYP450) is a specific
enzyme that is responsible for drug
metabolism
• Some drugs can induce or increase the action
specific to CYP450 which effects how the
drugs work in the body
• Not all CYP450’s are created equal
 CYP450
There are genetic differences in the way it works

CYP2D6
CYP450 Possible Genetic
Mutations
Metabolizers

CYP2C19 -Poor
-Intermediate
CYP2C9
-Extensive
-Ultra-rapid
Paclitaxel is
metabolized
by the This provides a possible explanation as
CYP450 to why some patients tolerate drugs
pathway better than others
Immune Response

Cytokine-Release
Syndrome, allergic
reaction, and anaphylaxis
reaction all equate to an
Immune Response
Immune Response
-A coordinated response to
cells and molecules in the
immune system
-The body’s protection from
bacteria, viruses and
foreign substances
-Is normally protective but
can cause unfavorable
effects

Porth & Matfin, 2009

 Innate Immunity (non-specific)
• The body ’s primary line of
defense

• Contains compliment
proteins, granulocytes, mast
cells, macrophages, dendritic
cells and natural killer cells
 Adaptive Immunity (specific)
• Responds less rapidly than innate immunity but
more effectively
• Includes lymphocytes , T cells (in cell mediated
immunity and B cells (in humoral immunity)
• Immunologic memory; more rapid and efficient
with subsequent exposure
Innate and Adaptive Immunity Cells
Click on the pictures to learn more…
Innate
Dendritic cell Mast Cell
Adaptive

B Cell
Compliment
Macrophage Protein

T Cell

Natural Killer Granulocytes

Cell
 Adaptive Immunity: Two Types

Cell-Mediated
Humoral Immunity
Immunity
Functions to get rid of One of the main parts of the
pathogens. T-cells develop immune system that triggers
receptors that identify the specific B-cells to produce and
viral peptides displayed on secrete large amounts of
specific antibodies. These are
the surface of infected cells created to fight a particular
and then turn on the microorganism or virus.
destruction of infected cells

Porth & Matfin, 2009

 Time out…let’s reflect!

Adaptive immunity has to do with which cells…

Mast Cells
Nope, think B-Lymphocytes
again! You’re correct! Is
there another
one?

Macrophages T-Lymphocytes
Sorry, this is r/t Way to go! Is
innate there another
one?
 Normal Immune Response vs.
Hypersensitivity Reaction (HSR)
HSR’s are different from the normal immune response. There are
four different types of immune responses. The Type 1 (IgE
response is related to HSR’s.
Type of Mechanism of Action
Immune
Response
1 Immediate Immunoglobulin E-mediated (IgE)
reaction

2 Antibody-mediated reaction resulting in antibody

–antigen complexes

3 Immune complexes form in the circulation and

deposit in various tissues

4 Delayed reaction which involves activation of T-

cells in the immune system

Gobel, 2005
 IgE Mediated Response
Allergen Now What!?!?
Eosinophils

Histamines
Antigen Presenting Cells Leukotrienes

T cytokines
Dendritic B Mast
Helper Cells
cells & B Cells Cells
cells
Present T cells are Isotypes are Mast cells bind
processed activated and induced , to antigen via
peptides from release IL-4, IL- generates IgE IgE antibody
the allergen 13
 What does this really mean?…your
patient is in TROUBLE!!!
Chemotherapy (Antigen)
Infusing

The body says, “HOLY MOLY, something is not right!”

IgE antibodies Mast

are produced Cells Histamines
and bind to Leukotrienes, &
receptors on prostaglandins
Mast cells start to circulate
basophils
 Time out…Let’s reflect

An allergic reaction is caused by an

IgE response in cell-mediated
immunity
True or False?
 What’s the problem?
The first mediator to be released during and acute
Histamines inflammatory reaction. Causes dilation of the arterioles and
increases vascular permeability. Stimulates H1 and H2
receptors.

-trigger contractions in the smooth muscles lining the trachea;

their overproduction is a major cause of inflammation during
a reaction. Leukotrienes are produced in the body from Leukotrienes
arachidonic acid. Enhance vasodilatation, increase mucous
production, and contraction of smooth muscle

Induce vasodilatation, viscous mucous production,

Prostaglandins hypotension, increased platelets begin to stick
together
Signs/Symptoms of HSR’s Quiz yourself by
clicking on the system
Chest pain, palpitations, to see how each can
hyper/hypo-tension, be affected
edema, cardiac arrest
Cough, dyspnea, nasal congestion,
wheezing, bronchospasms,
Headache, dizziness, hypoxemia, chest tightness,
confusion, LOC, anxiety, tacypnea
Impending doom

Incontinence, uterine cramping,

Nausea/Vomiting, pelvic pain, renal impairment
Diarrhea, abd
cramping, bloating

Skin Rash, pruritis, urticaria,

flushing, tearing
 “I have a tickle
in my throat.” “I don’t know
“Hey, Nurse could you what is wrong,
get me a blanket, it’s I just don’t
freezing in here!” feel right.”

Other signs that

your patient may
be reacting…
Confusion Anxiety
Restlessness
 Time out…let’s reflect
Your patient is midway through the infusion on her
ninth cycle of carboplatin for ovarian cancer. She
begins to complain of a “scratchy throat,” palmar
itching and slight shortness of breath. Based on
her symptoms, you would suspect:

A. Paresthesia of her vagus nerve cause by

carbolatin
B. An impending pulmonary embolus
C. An hypersensitivity reaction to carboplatin
Grade Allergic Reaction Anaphylaxis
1 Transient flushing or rash, drug N/A
fever <38 degrees C (<100.4
degrees F); intervention not
indicated
2 Intervention or infusion N/A
interruption indicated; responds
promptly to symptomatic
treatment (e.g., antihistamines,
NSAIDS, narcotics);
prophylactic medications
indicated for <=24 hrs
3 Prolonged recurrence of symptoms Symptomatic bronchospasm, with or
following initial improvement; without urticaria; parenteral intervention
hospitalization indicated for indicated; allergy-related edema;
clinical sequelae (e.g., renal Hypotension
impairment)
4 Life-threatening consequences; Life-threatening consequences;
urgent intervention indicated urgent intervention indicated
5 DEATH DEATH

National Cancer Institute, 2010

 Cytokine-Release Syndrome
(CRS)
A cluster of symptoms associated with the
use of monoclonal antibodies. It results
from the release of cytokines from cells
targeted by the antibody. As tumor cells
are destroyed levels of cytokines and
histamines increase.

Breslin, 2007
 Cytokines
• A group of polypeptide proteins that are made
and released by most cells in the body
• Organize communication between cells
• Manage responses among the innate and
mediated immune responses
• Trigger lymphocytes and other immune effector
cells
• Synchronize the damaged of cells targeted by
Monoclonal Antibodies (MOAB’s)

Breslin, 2007
 Cytokine-Release Syndrome
Monoclonal Cancer
Antibody Cell

Immune Compliment
effector cells
Cytokines release
into blood stream
Cancer
Cell
Cell Death

Breslin, 2007
Cytokines Release can cause…
• Fever
• Chills
• Rigors
• Nausea
• Vomiting
• Dyspnea
• Hypotension
 Time out…let’s reflect!
True or False, CYTOKINES:
Are a group of polypeptide proteins that
True! are produced and secreted by
most cells in the body.

True!
Act as chemical messengers, facilitating
communication between cells.

True! Coordinate responses among the innate

and mediated immune responses.
Clinical Symptoms of CRS
Cytokine-Release
Syndrome can present
almost the same as type
one (IgE) reactions and
can develop into
anaphylaxis-like
reactions…the difference
is the pathophysiology!
 Grades of Cytokine-release syndome
Grade 1 Mild reaction; infusion interruption not indicated; intervention not
indicated

Grade 2 Therapy or infusion interruption indicated but responds promptly

to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV
fluids); prophylactic
Grade 3 Prolonged (e.g., not rapidly responsive to symptomatic medication and/or
brief interruption of infusion); recurrence of symptoms following initial
improvement.

Grade 4 Life-threatening consequences; pressor or ventilatory support indicated

Grade 5 DEATH

National Cancer Institute, 2010

 What else is going on during a
reaction?
Generalized Adaptation Syndrome
(GAS)
General: the effect has to do with a general
systemic reaction
Adaptation: the response is due to a stressor
Syndrome: the physical manifestations are
dependent on each other.

Porth & Matfin, 2009

 GAS and Reactions
Three Stages
Alarm: generalized
stimulation of the This response is triggered by
Sympathetic Nervous a stressor. For cancer
System (SNS) patients this could be
Resistance: the body selects external or internal factors
the most optimal way to such as medication, anxiety,
respond environment, social support,
Exhaustion: stressor is &/or life experiences.
extended, start to see
possible signs of systemic
damage

Porth & Matfin, 2009

 GAS and Reactions

Have you ever thought

that your patient’s stress
or anxiety may have
caused a reaction?
Stress response depends
on what a person
expects to happen in a
given situation based
on previous learning
experiences.
 SNS in Stress!!
Adrenal Medula releases
Epinephrine and Norepinephrine

Increased
Increased
Blood
Heart Rate
pressure
Results in

Blood vessels increase

Increased pressure muscle tissue to
Glucose, fat, cholesterol control increased
can damage artery
in blood clump together blood flow
lining
and create plaque

All can lead to

stroke/ MI
 Time out…let’s reflect…

What effect does the release of

norepinephrine and epinephrine cause?
Select all that apply:

Correct! Increase in BP Correct! Increase in HR

Incorrect Decreased in HR
incorrect! Decrease in BP
Management and the Role
of the Oncology Nurse
 Nursing Interventions

Are you ready to Preventative Measures

administer the • Obtain baseline assessment &
vitals
Chemotherapy or • Assess for risk factors
Biotherapy infusion? • Educate the patient about
signs/symptoms of a HSR?
• Make sure emergency
medication/equipment
supplies are readily available?
• Confirm that the patient took
their pre-treatment
medications if ordered?
• Administer pre-medications as
ordered?
 Emergency Supplies
Equipment Medications
• Code Cart • Normal Saline
• Oxygen supplies • Epinephrine
• Ambu Bag • Albuterol Inhaler
• Stethoscope • Diphenhydramine
• Suction set-up • Famotidine
• Syringes/Needles • Dexamethasone
• Hydrocortisone
 Medications:
Histamine Antagonist
A histamine antagonist, commonly referred to as
antihistamine, is a drug that inhibits action of
histamines by blocking it from attaching to
histamine receptors.
Bind to H1 and H2 receptors and act competitively
to antagonize many effects of the inflammatory
response.
It may be necessary to give H1 and H2 antagonists
may be necessary to counteract the histamine
release.
 Medications: IV Fluids
• Maintain IV line with Normal Saline (NS)
• IV fluids should be given to maintain a
systolic BP above 90 mmHg

Watson, 2010
 Your patient is reacting!...
now what?
Stay in Control!!!!
-Stop the infusion
-Maintain IV line with NS or appropriate solution
-Stay with the patient and have co-worker activate
emergency team or notify physician
-Maintain Airway (administer O2 if needed)
-Monitor vital signs Q2 minutes until patient the patient
reaches near baseline vital signs
-Administer emergency medications
-Place the patient in supine position (if not vomiting or
SOB)
-Offer emotional support of patient and family

Polovich et al, 2009

 Documentation of HSR
• Pre-infusion assessment
• Initial symptoms and
• Prompt and accurate course of progression
documentation of a HSR
is critical • Timing of reaction and
duration
• Accurate grading will
allow the prescriber to • Grade and type of HSR
decide the next • Timing of interventions
appropriate steps for and patient response
treatment • Did the symptoms
resolve?: when/how?
Vogel, 2010
 Let’s apply what you’ve learned!
Case Study
Mrs. Jones, age 68, arrives at the Hematology/Oncology
clinic to receive her first chemotherapy for stage IV
ovarian cancer. Her baseline vitals are: BP: 148/62, pulse:
80, respirations: 20, oxygen saturation: 98%. You
administer premedications: dexamethasone 20mg IV,
diphenhydramine, 25mg IV, famotidine, 20 mg IV, and
zofran 8 mg, IV. The following chemotherapy was
ordered: paclitaxel 175mg/m2 infusion over 3 hours and
carboplatin AUC 6 (750 mg) over one hour. Five minutes
after you begin the infusion, Mrs. Jones complains of
itching, SOB and she is nauseated.
Vital signs are now: BP: 92/52, pulse: 120, Respirations:
30 and oxygen saturation is 82%. What is your immediate
response?

Incorrect Continue to monitor the patient

Incorrect Slow the infusion down

Incorrect Assure the patient she will feel better in no time

Correct! Stop the infusion

Myers, 2000
 In conclusion…
• How does this tutorial encourage you to
change your practice when thinking about
HSR’s?
• Nurses play a key role in preventing HSR’s
• Continue to be advocate for your patients!

THANK YOU FOR VIEWING THIS

TUTORIAL!!!
 References
• Bonosky, K. (2005). Hypersensitivity reactions to oxaliplatin: what nurses need to
know. Clinical Journal of Oncology. 9 (3), 325-330.
• Breslin, S. (2007). Cytokine-release syndrome: overview and nursing implications.
Clinical Journal of Oncology. 11(1), 37-41.
• Gobel, B. H. (2005) Chemotherapy-induced hypersensitivity reactions. Oncology
Nursing Forum, 32, 1027-1035.
• Gleich, G.J., & Leiferman, K.M. (2009). Oncology infusion reactions associated with
monoclonal antibodies. Oncology. 23 (2), 7-13.
• Labovich, T.M. (1999). Acute hypersensitivity reactions to chemotherapy. Seminars
in Oncology Nursing. 15 (3), 222-231.
• Lemos, M.L. (2006). Acute reactions of chemotherapy agents. Journal of
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• Liebermann, P., Nicklas, R., Oppenheimer, J., Kemp, S., & Lang, D. (2010). The
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reactions. The Oncologist. 12:601-609
• Myers, J.S. (2000). Chemotherapy-induced hypersensitivity reaction. American
Journal of Nursing. 100(4), 53-55.
 References
• National Cancer Institute. Common Terminology Criteria for Adverse Events v4.03
(CTAE). Published date June 14, 2010. Available at
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf. Accessed March 9, 2011.
• Polovich, M., Whitford, J. M., & Olsen, M. 2009. Chemotherapy and Biotherapy
Guidelines and Recommendations for Practice. 3rd edition. Oncology Nursing
Society.
• Porth, C.M., 2009. Pathophysiology, 7th edition. Lippincott.
• Scripture, C.D., Sparreboom, A., & Figg, W. (2005). Modulation of cytochrome p450
activity: implications for cancer therapy. The Lancet. 6;780-789.
• Timoney, J., P., Eagan, M., M., & Sklarin, N. T., Establishing clinical guidelines for the
management of acute hypersensitivity reactions secondary to the administration
of chemotherapy/biologic therapy. Journal of Nursing Care Quality, 18(1) 80-86.
• Vogel, W.H. (2010). Infusion reactions: diagnosis, assessment and management.
Clinical Journal of Oncology Nursing. 14, 10-14.
• Viale, P.H., & Yamamoto, D.S. (2010). Biphasic and delayed hypersensitivity
reactions: implications for oncology nursing.
• Watson, L.E. (2010). Recognition, assessment and management of anaphylaxis.
Nursing Standard. 24 (46), 35-39.