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New Insights on Who Should Take Erbitux for Colon Cancer
Date:10/26/2010

By Amanda Gardner
HealthDay Reporter

TUESDAY, Oct. 26 (HealthDay News) -- New research challenges previous assumptions about how to treat metastatic colon cancer in patients with a certain genetic mutation.

While guidelines have recommended that people with this type of cancer and mutations in their KRAS gene should not receive the targeted therapy cetuximab (Erbitux), a new study finds that a subset of these patients might actually benefit from taking the drug.

"Those drugs [cetuximab and its sister medication, panitumumab (Vectibix)] have been shown in a number of other studies to be less effective in patients who have mutations of the KRAS gene," explained Dr. Durado Brooks, director of colorectal cancer at the American Cancer Society. "Those studies have been so convincing that the National Comprehensive Cancer Network [which produces treatment guidelines] added KRAS testing as an element of decision-making for using these drugs to determine whether or not these drugs are likely to be useful."

This new study, appearing in the Oct. 27 issue of the Journal of the American Medical Association, suggests that researchers and clinicians both may need to drill down further in attempting to decipher which patients will benefit most from different targeted therapies.

"Before, we have been lumping [different] KRAS mutations together," Brooks said. "This current article is saying we may have been overly simplistic in our approach."

"It's a provocative report," added Dr. Steven Cohen, a medical oncologist with Fox Chase Cancer Center in Philadelphia. "The mantra has been to lump [the two KRAS] mutations together. This gives us reason to second-guess ourselves that we should not be excluding patients [with this one mutation] from this type of treatment."

Here, a group of European researchers looked at 579 patients for whom chemotherapy had not worked and who had taken cetuximab in previous clinical trials.

For the analysis, patients were separated out, depending on whether they had the KRAS codon 12 mutation or the KRAS codon 13 mutation.

Patients with the KRAS codon 13 mutation who were treated with cetuximab lived an average of 7.6 months, versus 5.7 months in those with the other mutation. Also, an average of four months transpired before disease progression, versus about two months in the control group, the investigators found.

Those with the KRAS codon 13 mutation didn't respond as well to the drug as people with a normal version of the gene, but they still responded.

While some experts may quibble with the study's methodology -- pooling data from several already-completed trials -- this may be the only way that enough patients with this relatively rare (codon 13) mutation could be collected for a legitimate analysis, Cohen noted.

Maybe 5 percent of patients with metastatic colorectal cancer, which is cancer that has spread, have this particular KRAS mutation, Cohen said.

Not only will more research need to be done before giving cetuximab to people with the codon 13 mutation becomes common practice, but doctors, the cancer network and insurance companies will have to get on board, Cohen noted.

The cost of cetuximab can be $3,000 a week or higher (the treatment is delivered weekly).

"It's a major cost issue," Cohen said.

More information

The U.S. National Cancer Institute has more on treatments for colorectal cancer.

SOURCES: Durado Brooks, M.D., director, colorectal cancer, American Cancer Society, Atlanta; Steven Cohen, M.D., medical oncologist, Fox Chase Cancer Center, Philadelphia; Oct. 27, 2010, Journal of the American Medical Association


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