DNA May Predict Benefit of Lung Cancer Treatment

Two-gene test could help some patients avoid unnecessary chemotherapy, researchers say

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HealthDay Reporter

WEDNESDAY, Feb. 21, 2007 (HealthDay News) -- A genetic test holds promise for identifying which early-stage lung cancer patients would benefit from chemotherapy and which would be better off without it, researchers report.

The test might also work in a similar way for patients with other malignancies, the experts said.

The test measures the activity of two genes that act to preserve the function of DNA, molecules that carry the information that make cells work.

"Both genes come into play when we are starting to treat people with chemotherapy," explained lead researcher Dr. Gerold Bepler, an oncologist with the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla. "If the activity of these genes is high, they are capable of repairing cells. That is good because it means the cancer is not as aggressive. But [the genes] can counteract the effects of chemotherapy."

High activity of these two genes, dubbed RRM1 and ERCC1, indicate that a lung cancer patient would do better without post-surgery chemotherapy, while low activity showed a need for treatment with cancer-fighting drugs, Bepler said.

The study, which is published in the Feb. 22 New England Journal of Medicine, included 187 patients who had surgery for early-stage non-small-cell lung cancer and were not given chemotherapy.

The average survival time for those with high activity of the RRM1 gene was more than 120 months, compared to 54.5 months with those who showed low activity.

"The survival advantage was limited to the 30 percent of patients with tumors that had a high expression of both RRM1 and ERCC1," the researchers wrote.

"If the activity is high, the cancer is not likely to spread," Bepler said. "If it is low, the patient is more likely to benefit from chemotherapy."

The next step toward medical use of the genetic test is a multicenter trial that "is in the process of being approved," Bepler said. "We plan to start the trial by the end of this year, and we hope to have results in two to three years."

Because drugs used to treat lung cancer are often used against other malignancies, the test could help determine treatment patterns for a number of tumor types, he added.

"We are getting ready to test the same thing in sarcomas, and it is also applicable to breast and colorectal cancer," Bepler said.

"It certainly could be extended to many other forms of cancer," said Dr. Adi F. Gazdar, deputy head of the Harmon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center in Dallas.

Gazdar, who wrote an accompanying commentary in the journal, added an important qualifier.

"Someone totally independent has to confirm this data," he said.

Testing activity of the two genes provides "a unique situation," Gazdar added. "You can use this to benefit the patient no matter what the results are. If gene activity is high in the early stages of cancer, you don't need to treat the patient with chemotherapy. If it is low, you think of putting the patient on adjuvant chemotherapy. This is a novel type of methodology."

The test procedure might require some modification, Gazdar said. In its current use, he said, patients are divided into two groups -- those who get chemotherapy and those who do not. Such a division might be too sharp, and the dividing line might need to be a bit fuzzier, he said. "Perhaps we need some refinement in the technique," Gazdar said.

More information

There's more on the genetics of cancer at U.S. National Cancer Institute.

SOURCES: Gerold Bepler, M.D., Ph.D, oncologist, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., and professor, oncology and medicine, University of South Florida, Tampa; Adi F. Gazdar, M.D., deputy head, Harmon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas; Feb. 22, 2007, New England Journal of Medicine

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