Precautions During Chemotherapy and Immunotherapy: What Is an Infusion Reaction?

Chemotherapy and immunotherapy are essential cancer treatments. Infusion, the method used to administer these medicines, delivers them directly into the bloodstream through a vein. Although it provides effective treatment, it can cause side effects such as infusion reactions.

Infusion reactions can occur while chemotherapy medicines are administered intravenously (IV, into a vein) and may vary in severity. This article provides important information on understanding, recognizing and managing reactions during chemotherapy, immunotherapy and other intravenous cancer treatments. It aims to help healthcare professionals and patients become more aware of and better prepared for these side effects, contributing to safer and more effective treatment.

What Is an Infusion Reaction?

Infusion reactions are a common side effect that may occur during or after intravenous (IV) medicine administration, ranging from mild to life-threatening.

The body may mount a strong immune response to certain treatments, such as intravenous cancer therapies, resulting in an infusion reaction.

Infusion reactions may occur immediately after an infusion or some time later.

Severity can vary depending on several factors, including the specific medicine, its dose and the person's health.

A 2018 study divided adverse reactions to treatment into several categories represented by letters:

1. (Augmented): Increased pharmacological effects
2. (Bizarre): Unusual effects
3. (Chronic): Chronic effects
4. (Delayed): Delayed effects
5. (End): Effects at the end of treatment
6. (Failure): Treatment failure

Classification of Infusion Reactions

Infusion reactions are generally unpredictable adverse effects. They are not dose-dependent and are usually unrelated to a medicine's specific effects. These reactions typically resolve on their own at the end of treatment.

Infusion reactions during cancer treatment are generally:

• Unpredictable
• Not dose-dependent
• Usually unrelated to the medicine's effects
• Self-resolving at the end of treatment

However, reactions to taxane chemotherapies such as paclitaxel and docetaxel, to carboplatin and especially to immunotherapy medicines may sometimes be predictable, as they often vary by drug type. In other words, reactions caused by immunotherapy may sometimes be anticipated based on the medicine's properties.

Allergic and Nonallergic Reactions

Infusion reactions can also be divided into allergic and nonallergic subtypes. Allergic infusion reactions involve an excessive immune response and may include severe reactions such as anaphylactic shock.

Immune responses are described as innate, adaptive or a combination of both.

An innate immune response is a general, rapid response by the immune system. An adaptive immune response involves a more targeted response when the immune system recognizes a trigger.

Nonallergic infusion reactions may include:

• Pseudoallergic reactions, such as cytokine release syndrome
• Idiosyncratic reactions that are unpredictable, unrelated to the medicine and rare
• Intolerance reactions occurring in response to a medicine

A 2018 study reported that most infusion reactions are nonallergic.

Infusion reactions can be mild or severe enough to require emergency medical attention and usually occur within 30 to 120 minutes after infusion. However, symptoms may sometimes begin between 24 hours and one week later. This underscores the need for vigilance after an infusion, regardless of the reaction type.

Infusion Reactions Associated with Cancer Treatments

Side effects of cancer treatment, including infusion reactions, are graded from 1 to 5 according to severity. Grade 1 indicates mild symptoms, while grade 5 represents the most severe outcome: death.

A 2019 systematic review found that about 5% of patients receiving monoclonal antibody medicines for colorectal cancer experienced infusion reactions. It showed that the frequency of these reactions may vary with their severity and the type of treatment used. These findings provide important information for understanding and managing the side effects of cancer medicines.

Infusion reactions may be caused by chemotherapy and can be serious. However, a 2017 study found chemotherapy-related infusion reactions to be rare. Another study in 2022 found that fewer than 5% of patients receiving immunotherapy experienced infusion reactions. These findings help clarify the side-effect profiles of different cancer treatments.

Features of Infusion Reactions to Taxane Chemotherapy (Paclitaxel and Docetaxel)

Taxane chemotherapies such as paclitaxel and docetaxel can cause immediate hypersensitivity reactions in about 5-10% of patients. These reactions can often be managed safely with measures such as taking corticosteroid tablets like Kordexa before restarting treatment. Although usually not serious, they can be significant for some patients and require professional management.

Symptoms of taxane-related infusion reactions may include rash and itching, back and lower back pain, facial or throat swelling, shortness of breath, a rapid heartbeat and sometimes low blood pressure. They usually appear within the first few minutes of treatment and may require stopping the infusion or reducing its rate.

What Are the Features of Carboplatin-Related Infusion Reactions?

Carboplatin-related infusion reactions are generally allergic. They may become more common after the 5th or 6th treatment cycle. Routine Kordexa before carboplatin is not recommended.

Carboplatin-related infusion reactions may involve rash, itching particularly on the hands, redness, facial or throat swelling, shortness of breath, a rapid or irregular heartbeat and sometimes low blood pressure, generally beginning during or immediately after treatment. In some cases, these reactions can be severe and require immediate medical attention.

What Are the Features of Oxaliplatin-Related Infusion Reactions?

Oxaliplatin-related infusion reactions generally occur through an IgE/mast cell-mediated mechanism, with symptoms involving the skin, respiratory, cardiovascular and other systems. Reported rates range from 2% to 25%, and some studies report a 21% rate of treatment discontinuation due to these reactions. The risk of grade 3-4 reactions is about 1.6%, and that of life-threatening reactions about 1%. Because these reactions are IgE-mediated, they occur after repeated exposure to the medicine. One study reported that reactions generally occurred during the seventh to ninth infusion, while some studies described two peaks at the third and sixth cycles.

Features of oxaliplatin-related infusion reactions include rash, urticaria, angioedema, bronchospasm and, rarely, hypotension. Immediate epinephrine is vital in severe anaphylaxis. Treatment options include stopping the oxaliplatin infusion and administering corticosteroids, histamine blockers, IV normal saline and oxygen.

Infusion Reactions Unrelated to Cancer Treatment

Infusion reactions can occur during other IV treatments as well as cancer therapy. Another study in 2022 examined adverse effects of iron infusions for iron deficiency. It included more than 12,000 people with iron deficiency and found an infusion reaction rate of about 3.9%. Only two people had severe reactions requiring epinephrine (EpiPen). Most others who experienced reactions had only mild symptoms.

What Are the Symptoms of Infusion Reactions?

Symptoms of an infusion reaction may begin during treatment, several days later or several weeks later.

General symptoms associated with infusion reactions include:

• Itching
• Flushing
• Hives
• Wheezing
• Shortness of breath
• Nausea
• Fever
• Edema

Most reactions are mild and may cause flu-like symptoms, including:

• Muscle pain
• Fever
• Rash
• Chills
• Headache
• Fatigue

In general, the sooner symptoms appear, the greater the likelihood of a severe reaction.

The Effect of Immunotherapy on Infusion Reactions

People receiving immunotherapy are unlikely to experience an infusion reaction. If one does occur, however, cytokine release is a possible cause. This may mimic anaphylaxis but requires different treatment.

Other side effects of immunotherapy may include:

• Infection
• Diarrhea
• Swelling and weight gain due to edema
• Palpitations
• Organ inflammation
• Sinus congestion

How Is an Infusion Reaction Diagnosed?

An infusion reaction is diagnosed when specialists, nurses or other healthcare professionals recognize its associated signs and symptoms. People should also watch for possible symptoms after returning home. If symptoms develop, they should consult a healthcare professional as soon as possible. If symptoms become severe, they should seek emergency care.

When a reaction occurs, specialists assess the symptoms and determine whether treatment is needed.

Anaphylaxis is a severe, rapidly developing allergic reaction that can be life-threatening. It results from an excessive hypersensitivity response and usually requires rapid medical intervention.

To diagnose anaphylaxis, symptoms must meet one of three main criteria:

1. Acute signs involving the skin or mucous membranes, with additional symptoms such as breathing problems or a sudden drop in blood pressure.

2. Two or more skin, respiratory, low blood pressure or gastrointestinal symptoms after exposure to an allergen.

3. A drop in blood pressure after exposure to a known allergen.

Blood or urine tests for biomarkers may also help diagnose anaphylaxis. These may include urinary histamine metabolites or blood tryptase levels measured after symptoms begin. However, anaphylaxis can occur without an increase in these chemical levels.

Treating Infusion Reactions

Treatment varies according to the type of infusion reaction. Mild reactions may not require treatment, although healthcare professionals may pause the infusion or slow its rate.

Moderate to severe reactions may respond to different medicines and treatments, including:

• Epinephrine for severe, potentially life-threatening reactions such as anaphylaxis
• Antihistamines
• Fluid resuscitation with a rapid saline (isotonic) infusion followed by a slower drip
• Atropine for bradycardia (a slow heart rate)
• Vasopressors to help raise blood pressure
• Corticosteroids

For nonallergic reactions, healthcare professionals generally stop the infusion and treat the symptoms. Once symptoms resolve, the infusion is resumed at half the previous rate.

Preventing and Managing Infusion Reactions

Treatment planning considers the patient's medical history, particularly previous infusion reactions. Although specialists cannot predict with certainty whether a patient will react in the future, this information can help assess risk and support better-informed planning of preventive measures.

Before an infusion, patients may be asked whether they have taken medicines sometimes called premedication. Premedication such as corticosteroids and antihistamines may help prevent infusion reactions. This precaution is important for reducing reaction risk and may help patients respond better to treatment.

Summary of Infusion Reactions and Their Management

Infusion reactions range from mild to life-threatening and may be allergic or nonallergic. Moderate to severe symptoms generally require symptom management and, in some cases, treatments such as lifesaving care for anaphylaxis.

It is not possible to predict whether someone will experience an infusion reaction. However, knowing their medical history and watching for signs of a potentially severe reaction can help maintain vigilance.

In summary, close monitoring and contacting the oncology team are important for any unusual symptoms or events after an infusion.