Study finds immune system can cause reaction to cancer drug

WASHINGTON (Reuters) - People who live in parts of the U.S. south may have pre-existing immunities that cause a severe allergic reaction to the cancer drug Erbitux, U.S. researchers reported on Thursday.

They found that patients who had sometimes life-threatening reactions had a pre-existing immunity to a sugar compound found in the drug made by ImClone Systems Inc..

The discovery, reported in the New England Journal of Medicine, might help explain why people living in certain regions of the United States are more likely to have the reaction, the researchers said.

And because the drug is so widely used -- it had global sales of $1.1 billion in 2006 for use in treating colon, head and neck cancers -- potential patients should be tested first, the researchers said.

Erbitux, known generically as cetuximab, is a monoclonal antibody, a genetically engineered immune system compound designed to home in specifically on cancer cells.

But some patients have a severe allergic reaction to the drug.

Dr. Thomas Platts-Mills of the University of Virginia and colleagues looked at reports of these cases, which suggest that as many as 22 percent of patients treated with Erbitux in Tennessee and North Carolina reported some kind of reaction, including anaphylaxis, which can rapidly lead to difficulty breathing, shock or fainting.

“It’s stunning,” Platts-Mills said in a telephone interview.

Even higher rates were reported from parts of Arkansas, Missouri and Virginia. But fewer than 1 percent of patients treated in the Northeast reported any reactions.


Tests showed a significant number of these patients were having immunoglobulin E or IgE responses -- the classic immune response that causes anaphylactic seizures. Many had them almost instantly after getting the drug, which suggests they had a pre-existing immunity, Platts-Mills said.

His team tested 538 people, including 76 cancer patients who got Erbitux in Tennessee, Arkansas and North Carolina and healthy volunteers from Tennessee, California and Boston.

Of the 76 cancer patients, 25 developed hypersensitivity reactions and 18 had IgE antibodies to the drug.

Of the noncancer patients, antibodies against Erbitux were found in 21 percent of the samples from Nashville, 6 percent of the samples from California and fewer than 1 percent of the samples from Boston.

“We all said why? Why on Earth would they have them?” Platts-Mills said. Possible culprits included ticks, roundworms and certain microbes.

Then Platts-Mills went on a mountain hike. “My feet started itching and I took off my shoes and there were all these baby ticks -- little ones,” he said.

He realized these small ticks. known locally as seed ticks, are found only in the south -- the same states where patients were reacting to Erbitux.

“We are making extracts of ticks to test people for IgE antibodies,” Platt-Mills said. “We need to know much more about the immune response to ticks in these people.”

“These intriguing research findings not only are potentially important to physicians treating certain cancer patients, but also may have broader implications for the use of immunotherapies for other diseases,” added Dr. Anthony

Fauci, director of the National Institute of Allergy and Infectious Diseases, which helped pay for the study.

Reporting by Maggie Fox; Editing by Xavier Briand