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Approximately 25 percent of patients in the United States develop allergies to chemotherapy, and these allergic reactions have prevented some cancer patients from getting the best treatment available for their cancer. Unfortunately, alternative chemo drugs are usually less effective and/or more toxic than the preferred options.
How are allergies defined in the context of chemotherapy?
An allergic reaction to chemotherapy is defined as an unexpected reaction with signs and symptoms that are not consistent with known toxicity of the drug (1).
Most of these reactions are suggested to be IgE-mediated release of histamines and cytokines (type I). However, some reactions called infusion reactions may also be caused by non-immune-mediated mechanisms (chemotherapy drugs, their metabolites, or the vehicles in which they are dissolved may also induce release of histamine or cytokines). Infusion reactions are difficult to distinguish from type I allergic reactions . There also are some reports of antibody mediated (type II), immune-complex mediated (type III), and cell mediated or delayed (type IV) allergies to certain chemotherapeutic agents.
Are allergies different from side-effects?
Side-effects are adverse reactions to drugs. Cytotoxic drugs used in chemotherapy work by killing the fast dividing cells. Though cancerous cells are the most susceptible to these drugs, other normal but relatively fast dividing cells can also be affected. Most chemotherapy side effects are due to this toxicity to normal cells, causing symptoms like hair loss, sores in the mouth and throat, kidney- and neuro-toxicity, and suppressed immunity. About 80% of all the side effects are common and predictable. An allergy to chemotherapeutics is a side effect which is not common, is unpredictable, and is unrelated to the known pharmacologic action of the drug .
Symptoms of Chemotherapy Drug Reaction/ Allergy
Allergic reactions occur within a few minutes to hours of drug administration (mostly by injection, rarely by the oral route).
Mild to moderate allergic reactions may include any of the following:
- Hives (raised, extremely itchy spots that come and go over a period of hours)
- Swelling of the tongue, lips, mouth, throat (also known as angioedema)
- Rash, itching, flushing
- Palpitations, Changes in heart rate
- Throat tightness
- Wheezing
- Coughing
- Trouble breathing
- Back/ abdominal pain
- Fever
- Nausea
Some allergic reactions can appear hours after the administration of drug and are typically type IV delayed type reactions.
A less common but more serious, sudden-onset allergic reaction to chemotherapy is anaphylaxis, which occurs in highly sensitive patients. Anaphylaxis occurs suddenly, can worsen quickly and can be deadly. Symptoms of anaphylaxis might include not only skin symptoms, but also any of the following:
- Tightness in the chest and difficulty breathing
- Swelling of the tongue, throat, nose and lips
- Dizziness and fainting or loss of consciousness, which can lead to shock and heart failure
These symptoms require immediate attention at the nearest Emergency Room. Epinephrine, the therapy of choice, will be given in this urgent care setting, but should also be self-administered via autoinjector as soon as possible by patients who have already been prescribed and are wisely carrying this device.
Some allergic reactions can appear hours after the administration of drug and are typically type IV delayed type reactions.
What type of chemotherapeutic drugs can cause allergies?
Nearly all chemotherapeutic agents used to treat cancer can cause allergic reactions, though with varying frequencies and severity. Anticancer drugs can be divided into 6 classes based on their mode of action: alkylating agents, mitotic inhibitors, antimetabolites, antibiotics, monoclonal antibodies and others. Drugs from any of these classes can cause allergic reactions. The table below shows the different frequencies of occurrence of allergy to various chemotherapeutic drugs.
| Alkylating agents | Mitotic inhibitors | Anti
metabolites |
Antibiotics | Monoclonal antibodies* | Others | |
| 1 | Cisplatin(1)
Oxaliplatin(3) Carboplatin(1) |
Teniposide
(1) Etoposide(2, 3) |
Rituximab(6)
Trastuzumab(6) |
Asparaginase
(1) Procarbazine (1) |
||
| 2 | Melphalan(3)
Cyclophosphamide (3) |
Mercapto-purine(1) | Doxorubicin(1) Daunorubicin(1)
Idarubicin(1) Epirubicin(1) |
Cetuximab(6) | ||
| 3 | Chlorambucil(1)
Ifosfamide(3) |
Vinblastine1
Vincristine1) Paclitaxel1,3) * Docetaxel1,3) * |
Azathioprine(1Cytarabine(3) # Fludarabine(3#
Fluorouracil (1, 3)# Methotrexate (1) |
Bleomycin(3) | Panitumumab(6 | Dacarbazine(1)
Hydroxyurea(1) |
- Frequent allergy, 2. Occasional allergy, 3. Rare allergy;
Severe allergy, Mild to severe allergy, Mild to moderate allergy, Uncertain
#– not enough evidence to suggest hypersensitivity vs. toxicity
*– infusion reactions (allergy like reaction to some component of the drug infusion)
What can we do to prevent or minimize chemotherapy allergies?
It is extremely important that the patients give their doctor information about any allergies and/or usage of any other medicines including over-the-counter or prescription drugs, vitamins, supplements or herbal medicine before starting the chemotherapy. This is because an exposure to certain compounds or allergens can increase the risk of developing an allergic reaction to the chemotherapy. The doctor can then decide the right medication. For certain drugs like Paclitaxel, antihistamines and corticosteroids can be given prior to the chemotherapy. Administering the drugs slowly over 30-60 minutes can help for some drugs e.g., Teniposide and Etoposide.
Once the allergic reaction starts, medical personnel can try to limit severity by various means. Possible actions include stopping the drug and administration of fluids, antihistamines, steroids and/or antipyretics.
Desensitization to the chemotherapeutic drugs is a newer method to reduce the severity and occurrence of allergic reactions during the course of chemotherapy . Patients should note and report any reaction however mild to the nurses and doctors, so as to prevent the onset of severe allergic reactions.
Chemotherapy Rapid Desensitization
If there is no suitable alternative to the medication that you are allergic to, you may need to undergo drug desensitization. This involves taking the drug in small increasing amounts until you can tolerate the needed dose with minimal side effects. This procedure must be performed in a closely monitored setting in a medical office or hospital where immediate medical care is available if problems develop.
Desensitization can help only if you are taking the drug every day. Once you stop it — for example, when a chemotherapy cycle ends — you will need to go through desensitization each time if you need the drug again.
The goal of drug allergy evaluation and desensitization is to enable our patients to take a full dose of the recommended medication to treat their disease (whether it is cancer, anemia, infection, aspirin for AERD, anesthesia for surgery, etc.) safely despite a history of an allergic reaction.
What to Expect
Desensitization to a certain medication involves giving the medication in slowly increasing amounts, starting with tiny doses, and ending with the full dose prescribed by the physician. The medication is given in the same format (oral, intravenous, or intraperitoneal), but starts more slowly and the process can take much longer.
Desensitization sessions usually last a total of 6 to 8 hours. Patients arrive at Nyack Hospital in the morning. After registration, the patient will be admitted to a monitored bed and will be closely observed by our physicians and nurses who have extensive education and experience in drug desensitization.
The Desensitization procedure begins with the patient taking “premedications” to help minimize any allergic reactions to chemotherapy. These may include oral antihistamines, steroids, montelukast, and acetaminophen. The patient may also be asked to take a steroid dose the night before the desensitization procedure.
If you have a reaction, the nurse will immediately stop the infusion, check your blood pressure and oxygen level, and treat your symptoms with medications, such as Benadryl for hives or swelling, a breathing treatment (albuterol) if you are short of breath or wheezing, or steroids and epinephrine if you have throat tightness or tongue swelling, or have a substantial drop in blood pressure. These symptoms will be treated immediately within the protocol guidelines.
If your symptoms are mild and resolve, the infusion will be restarted at the same rate, and the protocol will continue. If the symptoms are more severe and involve changes in your blood pressure, pulse, or respiration, the ICU doctors and/or the allergist on-call will examine you and decide how best to treat you.
If you do have a reaction, it is usually milder than your original reaction to your medication. Please tell the nurse if you notice any symptoms developing such as rash, hives, swelling, shortness of breath, chest or throat tightness, dizziness, palpitations, chest or back pain.
It is extremely rare that a reaction will be severe enough to prevent completion of your desensitization. It may take longer than originally planned, but the goal will always be to complete the infusion and to provide you with your needed medication.
Will I need to be desensitized again?
For drugs that are given on a daily basis, desensitization only needs to be performed once – as long as the medication is being taken daily, the body remembers and keeps a state of desensitization. Those medications include antibiotics used to treat infections, aspirin for prevention of heart attacks/ AERD, and insulin, used by diabetics.
Although studies have not been performed to test exactly how long a desensitization to medication lasts, it is generally agreed that if more than 2 days have passed since your last dose, the desensitization needs to be performed again. Thus, for patients receiving desensitization for chemotherapy and monoclonal antibodies, every dose of that medication needs to be given via this extended infusion protocol.
Your physician will decide how many times, and how frequently, you will receive this particular treatment. For patients receiving chemotherapy by desensitization, if all goes well, additional desensitizations may occur at outpatient facilities. This will be coordinated through your referring physician’s office.
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