* ALLERGIC REACTIONS
TO CHEMOTHERAPY
AMABELLE TRINA B GERONA, MD
* WHAT IS A SYSTEMIC ALLERGIC
REACTION?
* Drug hypersensitivity reaction (HSR)
* Adverse vents resembling allergy which occur at therapeutic dose
* Drug allergy
* When the immunologic mechanism is demonstrated
* PSEUDOALLERGIC REACTIONS / ANAPHYLACTOID REACTIONS
* Not directly immune mediated, but may be severe
* Due to indirect activation of immune system by the drug or by
excipient
Type DESCRIPTION MECHANISM PRESENTATION
I IgE mediated, immediate IgE mediated Anaphylaxis,
hypersensitivity angioedema,
bronchospasm
II Antibody dependent Tissue or cell Hemolytic
injury due to anemia,
binding of an Ag thrombocytopeni
or hapten to and a, neutropenia
Ab
III Immune complex disease complement Serum sickness
IV Cell mediated/delayed Activation of T Contact
hypersensitivity cells by Ag with dermatitis, SJS,
resultant tissue drug induced
damage hypertension
* WHAT IS A SYSTEMIC ALLERGIC
REACTION?
* Hypersensitivity (allergic reaction)
* Mild-moderate
* Severe reaction
* Acute infusion reaction (cytokine release)
* WHAT IS A SYSTEMIC ALLERGIC
REACTION?
* Hypersensitivity (allergic reaction)
consistent with type I hypersensitivity
IgE-mediated release of histamines, leukotriene and
prostaglandin from mast cells and basophils
rapid contraction of smooth muscle and dilation of
capillaries (urticaria, rash, angioedema, bronchospasm,
hypotension)
* WHAT IS A SYSTEMIC ALLERGIC
REACTION?
* Acute infusion reaction
interact directly with mast cells and basophils,
producing anaphylactoid response indistinguishable from IgE
mediated response
due to direct effects on immune cells
* AGENTS ASSOCIATED WITH SYSTEMIC
ALLERGIC REACTIONS
• Hypersensitivity (allergic reaction)
• Platinum
• carboplatin
• oxaliplatin
• Acute infusion reaction (cytokine release)
• Taxane
• Paclitaxel
• Docetaxel
• Monoclonal antibodies
* AGENTS ASSOCIATED WITH SYSTEMIC
ALLERGIC REACTIONS
• Hypersensitivity (allergic reaction)
• Platinum
• Carboplatin
• Occur in <1% if undergone <5 cycles of carboplatin
• 6.5% 6
• 7% 7
• 19.5% 8
• Usually, mild, itching, localized erythema, facial flushing and respond to oral
antihistamine
• 30-40% have severe reactions- occuring 30 mins after start of infusion
• Facial swelling, abdominal cramps, diarrhea, dyspnea
Annals of oncology. Prevention and handling of acute allergic and infusion reactions in Oncology. Joerger. 2012
* AGENTS ASSOCIATED WITH SYSTEMIC
ALLERGIC REACTIONS
• Hypersensitivity (allergic reaction)
• Platinum
• Oxaliplatin
• Causes HSR 0.5-25% -mild-mod
<1% severe/life-threatening
Causes itching, diffuse erythrodermia, bronchospasm, and evolve into
anaphylaxis in 1% of cases
Occur at 7-8th cycle of administration, 5-10mins after start
• Cisplatin
• Causeds HSR in 1-5%
• Mild reaction usually few mins after start of chemo, occur >6cycles after
Annals of oncology. Prevention and handling of acute allergic and infusion reactions in Oncology. Joerger. 2012
* AGENTS ASSOCIATED WITH SYSTEMIC
ALLERGIC REACTIONS
• Hypersensitivity (allergic reaction)
• Acute infusion reaction (cytokine release)
• Taxane
• Paclitaxel
• Due to type 1 cremophor (polysorbate 80)
• HSR occur in 30% without premedications
• <4% with premeds (antihistamine, steroids)
• Dose and rate dependent; occur at first exposure
• Disappear on rechallenge and premedications
• Sx: dyspnea, urticaria, hypotension
Annals of oncology. Prevention and handling of acute allergic and infusion reactions in Oncology. Joerger. 2012
* AGENTS ASSOCIATED WITH SYSTEMIC
ALLERGIC REACTIONS
CARBOPLATIN PACLITAXEL
Hypersensitivity Cytokine related
Provokes HSR after several cycles HSR after 1st or 2nd dose
Vary in timing and appearance of More uniform
severity
Hours to resolve Quickly resolve after discontinuation
No effective premends Effective premeds
Dexamethasone 3 days starting 1 day Dexamethasone 8mg 12 and 6 hrs
before chemotherapy before infusion
Diphenhydramine 2mg
Ranitidine 50mg 30 mins pre infusion
Annals of oncology. Prevention and handling of acute allergic and infusion reactions in Oncology. Joerger. 2012
* AGENTS ASSOCIATED WITH SYSTEMIC
ALLERGIC REACTIONS
• Hypersensitivity (allergic reaction)
• Acute infusion reaction (cytokine release)
• Taxane
• Monoclonal antibodies
• 50% human, >90% humanized antibodies and fully humanized antibodies 100%
• Rare, nonallergic, cytokine mediated HSR within first few hrs of infusion
• Rituximab 77% risk of cytokine release for first application
• Trastuzumab 40%
• Premedications: paracetamol, antihistamine
• Managed by: short-term cessation, antiHistamine blockers, restarting infusion
at slower rate
Annals of oncology. Prevention and handling of acute allergic and infusion reactions in Oncology. Joerger. 2012
Grade 1 Grade 2 Grade 3 Grade 4 Grade
5
Infusion -no -responds -not immediately -life threatening death
related interruption promptly to respond to intervention consequences; needs
reaction -intervention- intervention -symptom recurrence urgent intervention
none -prophylaxis if <24 -hospitalization
hrs indicated IF with
clinical sequelae
Allergic -no responds promptly -not immediately -life threatening death
reaction intervention to intervention respond to intervention consequences; needs
needed -prophylaxis if <24 -symptom recurrence urgent intervention
hrs -hospitalization
indicated IF with
clinical sequelae
anaphylaxis Symptomatic Life threatening death
bronchoscpasm +/- consequences
urticaria; IV
intervention
-allergy related edema
DIAGNOSIS OF SYSTEMIC ALLERGIC
REACTIONS TO CHEMOTHERAPY
Clinical + laboratory
Allergic reaction
(clin) flushing, urticaria, angioedema, shortness of breath,wheeze,
laryngeal edema, hpoxia, tachycardia, vomiting, diarrhea
(lab) IgE mediated immediate reaction with mass cells/basophils---
request for:
serum tryptase- develop serum peak 3 hrs after
development of anaphylactic reaction
-extract blood bet 15 min-3hrs after
development of allergy
DIAGNOSIS OF SYSTEMIC ALLERGIC
REACTIONS TO CHEMOTHERAPY
Clinical + laboratory
Infusion reaction
(clin) development of rashes, flushing, urticaria, hives
(lab) evaluate for fever, hypoxia, dyspnea, diarrhea
DIAGNOSIS OF SYSTEMIC ALLERGIC
REACTIONS TO CEHMOTHERAPY
Anaphylaxis is HIGHLY LIKELY if + in 1/3 criteria
1. acute illness within minutes to several hours with skin or mucosal
membrane involvement (hives, pruritus, flushing, swelling of lips)
AND AT LEAST 1 OF THE FF:
A. respiratory compromise with dyspnea, wheeze, bronchospasm,
stridor, hypoxemia or decreased expiratory flow
B. reduced blood pressure or symptoms of end-organ dysfunction
(syncope, collapse, incontinence)
DIAGNOSIS OF SYSTEMIC ALLERGIC
REACTIONS TO CHEMOTHERAPY
2. LIKELY allergen
a. Involvement of skin/mucosal membrane
b. respiratory compromise with dyspnea, wheeze, bronchospasm, stidor,
hypoxemia
c. reduced blood pressure or symptoms (syncope, collapse, incontinence)
d. persistent GI problems(crampy abdominal pain, vomiting)
3. Reduced blood pressure within minutes to hours after exposure to a known
allergen
SBP < 90mmHg or > 30 % decreased infants
PREVENTION OF SYSTEMIC ALLERGIC
REACTION TO CHEMOTHERAPY
* SKIN TESTING
* Not done for chemotherapy
* Irritative effects of chemo
* Negative results due to hypogranulation of mast
cells and baophiles
* Ideally, done to elicit type I IgE mediated
allergic reactions.
PREVENTION OF SYSTEMIC ALLERGIC
REACTION TO CHEMOTHERAPY
PREMEDICATIONS
NSAIDS prevents mild, non immune hypersensitivity
STEROIDS and severe hypersensitivity
but NOT anaphylactic reaction
MANAGEMENT OF PATIENTS WITH
ALLERGIC REACTIONS TO CHEMOTHERAPY
* ACUTE MANAGEMENT
* to stop the infusion and the intramuscular
administration of EPINEPHRINE 1:1 (most
important)
MANAGEMENT OF PATIENTS WITH
ALLERGIC REACTIONS TO CHEMOTHERAPY
* ACUTE MANAGEMENT
* EPINEPHRINE-
* SUPPLEMENTAL OXYGEN
* BLOOD TRANSFUSION
* IV FLUIDS
MANAGEMENT OF PATIENTS WITH
ALLERGIC REACTIONS TO CHEMOTHERAPY
* DESENSITIZATION
Induction of tolerance to an agent by administering small
amounts of the agent in the incremental up to the
therapeutic dose
Increasing exposure to the amount of allergen over a
prolonged time many over a prolonged time many of the
protocol chemotherapeutic agents require rapid
desensitization and are completed within hours.
*SUMMARY
HYPERSENSITIVITY (ALLERGIC, type I, IgE)
PLATINUM (carboplatin, oxaliplatin)
occur at repeated doses/cycles
mild-moderate reaction: no discontinuation, rechallenge
antihistamine, steroids, rechallenge
anaphylaxis: discontinue
epinephrine
NO rechallenge
ACUTE INFUSION REACTION (cytokine)
TAXANE (paclitaxel, docetaXEL
MONOCLONAL ANTIBODIES
occur within seconds/minutes in first or 2nd cycle
give premeds