Cancer Treatment Infusion Reactions

Introduction

Cancer treatments have the potential to cause infusion reactions (IRs). It is important to manage IRs because they may cause treatment disruption and require costly medical interventions. Both cytotoxic and biological agents cause IRs. In general, IRs can be anaphylactic or anaphylactoid.

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Anaphylactic IRs: Anaphylactic IRs are allergic in nature and are usually mediated by immunoglobulin E (IgE). Clinical symptoms do not vary widely among the agents, but the time course and severity of IRs differ among chemotherapeutic agents and range from mild to severe reactions. Severe reactions are rare but the incidence of mild to moderate reactions is quite high. IRs may affect any organ system in the body and range in severity from a mild rash to systemic anaphylaxis. Mild-to-moderate IRs usually cause flushing, rash, fever, rigors, chills, dyspnea, and mild hypotension. Severe reactions are typically characterized by hypotension, bronchospasms, cardiac dysfunction, anaphylaxis, and other symptoms.
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Anaphylactoid IRs: Anaphylactoid IRs present in a similar fashion as anaphylactic reactions; however, they are not IgE-mediated and are characterized by non–immune-mediated release of cytokines and immune mediators.

IRs from cancer treatments can be due to age-related factors, concomitant diseases, cardiovascular diseases, or concurrent medications. Apart from being aware of the potential risk of an IR from a specific drug, it is imperative for clinicians to recognize their symptoms, understand their pathology, and use optimal risk assessment and prophylactic regimens. Inappropriate assessment of the nature and severity of the reaction could negatively affect treatment decisions. This chapter reviews the features and management strategies of severe IRs for some, commonly used chemotherapy drugs and monoclonal antibodies.

Recognition of Infusion Reactions

Prompt recognition and immediate medical attention are needed to reduce the risk from IRs. IRs can have a significant negative impact on both patients and clinicians because these reactions usually occur while treatment is being administered or shortly thereafter.

Based on patient symptoms and status and available emergency resources, management of patients who suffer an IR from an anticancer agent is very individualized and varies with the severity of the reaction. Severe reactions are less frequent and may be fatal without appropriate intervention. IRs can also lead to significant anxiety in patients, distress to staff, and the use of substantial resources. It is important for clinicians to be aware of the possibility of IRs and have protocols in place to prevent and manage these reactions. Mild and moderate infusion reactions are characterized by transient symptoms without any signs or symptoms of anaphylaxis. Severe infusion reactions, by definition, are associated with any features of anaphylaxis such as respiratory compromise, angioedema, hypotension, or generalized urticaria.

Prevention and Treatment of Infusion Reactions

In general, antihistamines, histamine (H)2 blockers, and steroids are used to prevent infusion reactions. The most commonly used drugs are diphenhydramine (50 mg), ranitidine (50 mg), and dexamethasone (4–10 mg). Once an infusion reaction is suspected, consideration should be given to the severity of the reaction. True anaphylactic reactions should be treated just like anaphylaxis of any cause, with prompt airway management, administration of epinephrine, and emergency room evaluation. Tables 11.1 and 11.2 provide detailed recommendations for the prevention and management of IRs caused by various agents. Fig. 11.1 depicts a general treatment algorithm for mild to moderate and severe infusion reactions.

TABLE 11.1

Infusion Reactions With Frequently Used Humanized and Chimeric Monoclonal Antibodies

Incidence, Prevention, and Management
Drug	Incidence of Severe Infusion Reaction	Symptoms	Prophylaxis	Management
Humanized
Alemtuzumab ^,	3%	Shortness of breath, dizziness, hypotension, fever, headache, bronchospasm, chills, rash.	Premedicate with antihistamines, and corticosteroids.	Stop the infusion. Treatment can be resumed at a slower rate, after resolution of all symptoms.Antihistamines, and corticosteroids can be used to prevent infusion related events.
Bevacizumab ^,	<1%	Dyspnea, flushing, rash, chest pain, rigors, nausea, hypertension, wheezing, headaches.	Premedication is not recommended.	Treatment interruption; can be resumed at a slower rate after resolution of all symptoms. Supportive therapy.
Pembrolizumab ^,	<1%	Fever, chills	Premedicate with antihistamines.	Discontinue
Trastuzumab ^,	<1%	Chills, fever, anaphylaxis, urticaria, bronchospasms, angioedema, and/or hypotension	Premedication is not recommended.	Treatment interruption; can be resumed at a slower rate after resolution of all symptoms.
Chimeric
Rituximab ^,^,^,	∼10%	Fever, chills, rash, hypotension, nausea, rhinitis, urticaria, pruritus, asthenia, angioedema, bronchospasm. May be associated with features of tumor lysis syndrome.	Premedication: epinephrine, antihistamines, glucocorticoid.Close monitoring during all infusions for patients with preexisting cardiac and pulmonary conditions.A slow initial rate of infusion.	Treatment interruption; can be resumed at 50% reduction in infusion rate, after resolution of all symptoms.
Cetuximab ^,^,^,	3%	Chills, fever, urticaria, bronchospasms, angioedema, and/or hypotension.	Slower infusion rate.Premedication: epinephrine, antihistamines, glucocorticoid.	Treatment interruption; can be resumed at a slower rate after resolution of all symptoms.