Scientists puzzled by severe allergic reaction to cancer drug in the middle Southern US

A patient’s expectations about the side effects of chemotherapy usually focus on nausea, hair loss, fatigue and other side effects. Worries about severe allergic reactions to their therapy is usually not a concern.

A recent study from the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, the Vanderbilt-Ingram Comprehensive Cancer Center and the Sarah Canon Cancer Center in Nashville have identified an unusually high rate of allergic reaction in cancer patients living in the middle South who received a common drug used for treating their cancer.

This study was presented at the 43rd annual meeting of the American Society of Clinical Oncology in Chicago in June, 2007 and appears online Aug. 17th in the Journal of Clinical Oncology.

The drug, cetuximab, marketed by Bristol-Meyers Squibb as Erbitux, is a widely used chemotherapeutic agent for treating colon cancer, head and neck tumors, and is being studied in the treatment of ovarian, lung, breast and gastrointestinal tumors.

When cetuximab was first approved, the first three patients treated at UNC had severe reactions to the drug. Doctors at both Sarah Canon and Vanderbilt also had more patients than expected react with a drop in blood pressure and shortness of breath or other hypersensitivity reactions within minutes of infusion of cetuximab.

“After speaking with others, we realized that patients who lived on a line across North Carolina, Tennessee, northern Arkansas and southern Missouri had these adverse reactions to the drug,” said study leader Dr. Bert O’Neil, assistant professor of medicine, division of hematology and oncology at UNC. “So, we thought it appropriate to see what common bonds were there.”

Cancer researchers from UNC and Vanderbilt pooled their patients dating back to when the drug received approval from the Food and Drug Administration, in 2004. More than 140 patients from ongoing clinical trials (at Vanderbilt) and current clinical records (at UNC) were reviewed for the presence of immediate, severe hypersensitivity reactions as well as pertinent demographics to determine this region’s rate of allergic reactions and to see if a profile of the potentially allergic patient was evident.

The nationwide rate of severe allergic reactions to cetuximab is only about 2 percent. However, 22 percent of patients in this study showed severe allergic reactions to the drug. Cetuximab normally is infused over a two-hour period, but allergic patients had a reaction within minutes of starting the infusion, a classic anaphylactic reaction. The strongest predictor of a reaction to cetuximab was a history of other hypersensitivities, such as allergic asthma, food allergies, bee stings or allergies to other drugs, such as penicillin.

What is it about this strip across the middle South" “A good question,” said O’Neil. “The most likely places to look would be food- or plant-based allergens. If it is of plant origin, finding the source could be a needle-in-a-haystack search. And it’s a narrow geographic band; colleagues in Atlanta or the University of Virginia haven’t seen this type of reaction.”

The research team felt that clinicians in this middle South region must obtain a thorough history of allergic reaction and be prepared to use an alternative drug, such as panitumimab, for patients with a history of hypersensitivity reactions, O’Neil said.

“Bristol-Myers Squibb is studying a screening test for the specific factor that leads to the reaction. In the meantime, doctors in the middle South need to be aware of, and be prepared to treat, sudden, severe allergic reactions when using cetuximab,” O’Neil said.

Based on the results of this study, UNC has a physician, physician assistant or nurse practitioner present for the first 30 minutes of all infusions of cetuximab. The Sarah Cannon Cancer Center halted all studies the drug.

“This is a curious problem, but not a problem we can’t deal with,” said O’Neil. “As long as we know the patient’s allergy history, we know what to do.”

Source: University of North Carolina at Chapel Hill

Related stories:

Pediatric researchers find possible 'master switch' gene in juvenile arthritis
Researchers have found that a gene region known to play a role in some varieties of adult rheumatoid arthritis is also present in all types of childhood arthritis. The researchers say the responsible gene may be a "master switch" that helps turn on the debilitating disease.
Silencing of molecular 'conversation' may help curb severe allergies
Scientists in Sydney have identified a process, a synergistic encounter between two molecules, that may account for the extreme allergic reactions some people experience. By silencing at least one of these molecules, it may be possible to treat allergies.
Hayfever hope
With the peak grass pollen season approaching, scientists can reveal that a daily dose of probiotic can change the immune status of people with hay fever.
Researchers unravel heparin death mystery
An international team of researchers led by MIT has explained how contaminated batches of the blood-thinner heparin were able to slip past traditional safety screens and kill dozens of patients recently in the United States and Germany.
Researchers evaluating food allergy treatment
Researchers at National Jewish Medical and Research Center are conducting trials to evaluate a method to prevent allergic reactions to food. They are feeding peanut- and egg-allergic people increasing doses of an investigational protein extract from the foods to see if they can induce the participants’ immune systems to tolerate the food.
Researchers find cause of severe allergic reaction to cancer drug
Clinicians have been perplexed by the fact that some patients given the drug cetuximab—an immune-based therapy commonly used to treat persons diagnosed with head and neck cancer, or colon cancer—have a severe and rapid adverse reaction to the drug. Sometimes the reaction includes anaphylaxis, a life-threatening condition characterized by a drop in blood pressure, fainting, difficulty breathing, and wheezing.
Scientists move closer to developing a new class of asthma and allergy drugs
A team of Biotechnology and Biological Sciences Research Council (BBSRC) funded scientists has moved a step closer to developing a new class of effective asthma and allergy drugs. With new research published today in The Journal of Immunology, the team from Barts and The London School of Medicine and Dentistry has found an important target that holds significant promise for millions of people suffering from allergies, asthma, rheumatoid arthritis and a range of other inflammatory diseases. This work confirms that a key component of the body's own response to allergy-causing agents (allergens) can be targeted to reduce allergic reactions in mice.
Allergic-like reactions occur in premedicated patients
Allergic-like reactions can occur in patients (both children and adults) when given gadolinium containing contrast agents, even if they have been pre-medicated with corticosteroids and antihistamines, according to a recent study conducted by researchers at the University of Michigan Health Systems in Ann Arbor.

News discussion:

Medicine & Health news