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Chemo Benefits in Doubt for Early-Stage Colon Cancer Patients

Mayo Clinic says treatment may reduce survival time for 'substantial subset'

May 16, 2008

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Mayo Clinic researchers and collaborators say they have conclusively demonstrated that a substantial subset of colon cancer patients should not receive chemotherapy because it provides no clinical benefit, and actually may reduce survival time.

Research findings indicate that oncologists should use an existing test to check tumor subtype in certain patients before offering treatment. Patients who would benefit most from this test include those with locally advanced disease that has not spread to their lymph nodes, known as stage II disease.

The study, released May 15 as part of the 44th annual meeting of the American Society of Clinical Oncology, found that the 15 percent of patients with tumors defined as "deficient DNA mismatch repair" (dMMR) do not respond to 5-fluorouracil (5-FU) chemotherapy, which is widely used to treat colon cancer.

The study is a follow-up to one published in 2003 in the New England Journal of Medicine that suggested patients with dMMR tumors should not be treated with chemotherapy. Because the finding was so novel, confirmation of the results was required before they could be incorporated into clinical practice. This new work offers that confirmation, researchers said.

"We think it is very important for patients and their doctors to have this information before considering treatment in a patient with stage II colon cancer," says Daniel Sargent, Ph.D., a Mayo Clinic biostatistician who is presenting the study results. "It could save patients the toxicity, inconvenience and expense of treatment from which they will receive no benefit."

Simple laboratory tests for dMMR exist. They are currently used to check for hereditary colon cancer that also is characterized by the absence of mismatch repair proteins, says coauthor Stephen Thibodeau, Ph.D.

"Many clinical laboratories across the country already use these tests," he said. "Now that this study proves the case that dMMR testing should be part of standard diagnostic practice for the treatment of colon cancer, this can be easily incorporated into a clinical workup."

Research is ongoing to understand why patients with dMMR tumors can have a worse prognosis after chemotherapy treatment.

One theory is that because these cancer cells cannot repair damage from chemotherapy, the treatment induces mutations that can cause the cancer to become more aggressive. Another theory is that while these cancers produce a strong innate immune reaction, chemotherapy may dampen that beneficial response, resulting in increased cancer growth.

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