Allergies to medications are a well-known problem in medicine. They represent a reaction of a patient’s immune system to a drug where it mistakenly assumes that the drug is a harmful invader, such as a virus or bacterium. Such reactions can be mounted against virtually any drug, but certain drugs have proven to be more allergenic than others.
The most severe form of an allergic reaction is anaphylaxis. This is characterized by hives, flushing, weakness, laryngeal spasm, hypotension, upper respiratory tract collapse and, in its ultimate progression, cardiorespiratory arrest. I published a review of the epidemiology of anaphylaxis in 2001 in the Archives of Internal Medicine that was very heavily cited. In it, I reported that drugs were the second leading cause of anaphylaxis after foods. Among drugs, antibiotics were the most common allergens, especially penicillin, followed by radiocontrast media. Most other drugs were fairly uncommon.
Nonetheless, I always take the allergy part of the history first to insure that I am aware of potential allergens. Patients frequently confuse side effects to a drug as an allergic reaction so this may not be as straightforward as it seems.
As with other drugs, most chemotherapy drugs can provoke an allergic reaction as well. Notable in this category are the platinum drugs and the antibiotic drugs (bleomycin, mitomycin, etc.), and also monoclonal antibody drugs. The monoclonal antibodies are proteins and so these are more likely to act as antigens for the cells that produce antibodies. An antigen is a molecule or foreign substance which binds to a receptor on a T cell and provokes the production by B cells of antibodies or immunoglobulins.
The most common or serious type of allergic reaction is the type I reaction, which is IgE-mediated. In this type of allergic reaction, the antigen causes the production of an antibody known as immunoglobulin E or IgE which tends to bind to mast cells that contain histamine. This reaction leads to the release of the histamine, which causes most of the symptoms we associate with allergic responses. Anaphylaxis is an extreme form of this, with the release of massive amounts of histamine, leading to bronchospasm, laryngeal edema, and shock.
Oxaliplatin (Eloxatin) is from a class of drugs that contain the heavy metal platinum (including carboplatin and cisplatin). The presence of this heavy metal has led to significant toxicity from peripheral neuropathy as well as potential problems with renal excretion and renal toxicity, ototoxicity (hearing problems), and nausea. The precise mechanism of action of oxaliplatin is not known but it is believed that the platinum forms complexes with the DNA in the tumor cell, forms cross-links, and thereby blocks DNA synthesis. It was approved by the FDA in 2002 for use in the treatment of colorectal cancer in combination with a fluoropyrimidine (5FU or capecitabine); it is virtually never given alone as a single agent. It is also routinely used off-label for other GI malignancies, including gastric cancer and pancreatic cancer.
I focus on oxaliplatin because allergic reactions and anaphylaxis are common phenomena in its use. Allergic reactions will never occur on the first treatment since an allergic reaction generally requires prior exposure to the allergen. Hypersensitivity reactions to oxaliplatin occur starting with the second treatment and on, with increasing frequency, occurring in up to 20% of patients by the sixth or seventh treatment. For oxaliplatin, these reactions are generally IgE-mediated, and occur acutely during or immediately after the chemotherapy infusion. A prolonged break in the administration of chemotherapy for a time interval followed by resumption after weeks or months can increase the risk of an allergic or anaphylactic response.
After an allergic reaction, a skin test can be used to confirm the sensitivity to oxaliplatin. If confirmed, desensitization by a dermatologist or allergist who is experienced in its use can be utilized before re-challenging the patient with further oxaliplatin. These protocols require the administration of dilute doses of the drug in increasing steps over time, as well as the very slow administration of the drug infusions. They can be difficult to provide and to undergo and do have risk for the patient. While they have a high degree of success, one would want to feel very strongly that the use of continued oxaliplatin therapy was worth the risk and bother.
I have had many patients who have had significant allergic reactions to oxaliplatin, including anaphylactic reactions. Perhaps this has made me gun-shy, but I have never felt the need to re-challenge patients with further oxaliplatin after a clearcut allergic reaction.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
