© 2005 Oxford University Press
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In Brief
Revised Bethesda Guidelines Identify Patients at Risk for HNPCC
The revised Bethesda Guidelines for selecting individuals for genetic testing for hereditary nonpolyposis colorectal cancer (HNPCC) are effective for identifying patients at risk for the disease, according to a new study.
The revised Bethesda Guidelines for HNPCC made recommendations on which patients should receive genetic testing for HNPCC based on, in part, the presence of microsatellite instability. However, the most effective strategy for detecting gene mutation carriers has been controversial.
In the April 27 issue of the Journal of the American Medical Association, researchers tested tumors from 1,222 patients newly diagnosed with colorectal cancer. Patients whose tumors either exhibited microsatellite instability or lacked MSH2/MLH1 protein expression underwent genetic testing.
Genetic testing found seven patients with MSH2 mutations and four patients with MLH1 mutations. Strategies based on the revised Bethesda Guidelines—either microsatellite instability testing or the absence of MSH2/MLH1 protein expression—were the most effective for identifying MSH2/MLH1 gene carriers.
Randomized Trial of Gefitinib for Advanced Lung Cancer Closed Early
Researchers have closed a phase III randomized clinical trial of gefitinib (Iressa) versus placebo following chemotherapy and radiation for patients with non–small-cell lung cancer (NSCLC) that had spread only to nearby tissues or lymph nodes. Review of interim data indicated that the trial would not meet its primary endpoint of improved survival.
The patients in the study had inoperable stage III NSCLC and already had completed the combined chemotherapy regimen of cisplatin and etoposide with radiation, followed by docetaxel.
As of March 10, 2005, 611 patients had been enrolled in the trial, and 276 had been randomly assigned to one of the two arms. Detailed results from the study were scheduled to be presented May 14 at the American Society of Clinical Oncology Annual Meeting. The clinical trial was sponsored by the National Cancer Institute and was conducted by the Southwest Oncology Group.
Gene Copy Number May Be Associated With Response to EGFR Inhibitors
Increased copy number of the epidermal growth factor receptor (EGFR), but not mutations in genes that mediate EGFR signaling, may be associated with a patient's response to monoclonal antibodies such as cetuximab (Erbitux) and panitumumab, according to a new study.
A research team from Italy looked for genetic changes in tumor samples from 31 patients with metastatic colorectal cancer who had been treated with either cetuximab or panitumumab.
They found that eight of the nine patients who responded to the monoclonal antibodies had an increased EGFR copy number; only one of 21 nonresponders had an increased copy number. The researchers also looked at mutations in the EGFR catalytic domain; however, no mutations in these genes were found to be associated with disease response.
The authors also tested cetuximab in colorectal cancer cell lines and found that the drug completely inhibited the proliferation of cells that had an increased EGFR copy number but did not affect cells that had unamplified EGFR. The study was published online April 14 in The Lancet Oncology.
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