Patients with metastatic colorectal cancer unresponsive to irinotecan fare better when given a combination of irinotecan and cetuximab, according to a Merck-funded trial in the July 22 New England Journal of Medicine. Though cetuximab alone had significant therapeutic activity, the combination of the two drugs was more effective and cetuximab seemed to circumvent irinotecan resistance.
Cetuximab interferes with a cell-signaling pathway by blocking a site on a cell membrane protein called epidermal growth factor receptor (EGFR). EGFR proteins are involved in the process that causes cells to grow and proliferate; EGFR expression has been correlated with poor prognosis in colon cancer.
Scientists, led by Dr. David Cunningham of the Royal Marsden Hospital in London, treated 218 patients with both cetuximab and irinotecan and 111 patients with cetuximab alone. All patients had metastatic colorectal cancer that had not responded to previous treatment with irinotecan. The rate of response to therapy was greater in the group receiving both drugs: 22.9 percent of patients given combination therapy responded to treatment compared with 10.8 percent given cetuximab alone. The average time to further progression of the disease was also greater for those on the combination therapy (4.1 months) than for those on cetuximab alone (1.5 months).
Computer-based tutorials can be valuable tools in educating women at risk for hereditary breast cancer, according to a study in the July 28 Journal of the American Medical Association. In an NCI-funded study, Dr. Michael Green of Penn State College of Medicine and his colleagues compared an interactive computer program with routine one-on-one counseling to assess which method yielded better results between high-risk and low-risk women.
Researchers recruited 211 women for the trial, which compared face-to-face genetic counseling with a computer tutorial followed by genetic counseling. They found that the women's knowledge of genetic testing increased and their perception of risk decreased with both mechanisms. Reported anxiety was lower for women in the counseling group, regardless of risk status, but was unchanged for women in the computer group. However, low-risk women significantly decreased their intention to undergo genetic testing. Researchers concluded that the computer program might be substituted for face-to-face genetic counseling for low-risk women, but for high-risk women, it was more effective as an addition to personal genetic counseling.
Researchers have found new evidence that fatty acid synthase (FAS) protein may play an active role in the development of cancer. In a study published in the July 20 Proceedings of the National Academy of Sciences, scientists at Evanston Northwestern Healthcare in Illinois present evidence that in some cancer cells, FAS protein regulates expression of the cancer-causing gene HER2 and suggest FAS as a potential therapeutic target.
Previous studies have associated FAS overexpression with the development of aggressive breast and ovarian cancers; its role in the process, however, has been unclear. Many other genes for proteins involved in the manufacture of lipids - one function of FAS - are also overexpressed early on in many cancers. To determine whether FAS actively contributes to cancer development, researchers blocked the expression of FAS in malignant and normal cells with chemical inhibitors and RNA interference.
Using breast and ovarian cancer cells that overexpressed the HER2 gene (which is involved in cell growth and has been associated with poor prognosis in these cancers), the researchers found that levels of HER2 protein in these cells dropped dramatically when FAS was blocked. This suggests a molecular link between the two. When researchers targeted both FAS and HER2, the cancer cells died.
Examining these data, the scientists concluded that "FAS activity is necessary to integrate a number of signaling pathways that regulate metabolism, proliferation, and survival of HER2-overexpressing cancer cells." They write that their results provide rationale for developing therapies that target FAS in carcinomas overexpressing HER2.
Initial data from NCI's Lung Screening Study (LSS), published in the July issue of Chest, "convincingly demonstrate" the feasibility of carrying out a randomized controlled clinical trial to compare chest X-ray (CXR) and low-dose spiral CT (LDCT) for the early detection of lung cancer. The success of the LSS, which tested the viability of quick enrollment and willingness of high-risk patients to join a lung cancer screening trial and established the prevalence of abnormal findings on baseline screening and the extent of diagnostic follow-up, led to the initiation of the National Lung Screening Trial (NLST) in September 2002.
The LSS was conducted over a 12-month period, recruiting 3,318 participants from 6 sites also participating in the NCI's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Patients were randomized either to the LDCT or CXR arm, and subsequent screening was performed for lung cancer detection. For those receiving CT scans, 20.5 percent had a positive test (325 people) compared with 9.8 percent of those receiving CXR (152 people); after follow-up testing, 30 people in the LDCT scan arm were found to have lung cancer compared with 7 in the CXR arm. The study does not evaluate if this detection will reduce cancer mortality, although NLST is designed to answer that question.
Lung cancer is the leading cause of cancer death in the United States. Smokers are at highest risk for the disease, and although quitting smoking reduces risk, nearly half of all lung cancer cases occur in former smokers. Both the LSS and NLST recruited people at increased risk for lung cancer due to their smoking history.
Scientists at France's Institut Gustave-Roussy report that double-agent chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) increases tumor response and improved patient survival when compared with single- or triple-agent therapy. These meta-analysis results were published in the July 28 Journal of the American Medical Association.
In this Aventis-funded study, Institut researchers examined the results of 57 clinical trials conducted from 1980 to 2001 and totaling 11,160 patients. They included only phase III clinical trials performed on patients with advanced, inoperable NSCLC. Based on analyses of these data, the researchers found that adding a drug to single-agent chemotherapy resulted in a two-fold increase in tumor response rate (from 13 percent to 26 percent) and a 5 percent increase in the 1-year survival rate. In these trials, when a third drug was added to double-agent chemotherapy, the benefit was not significant. While tumor response rate increased from 23 percent to 31 percent, there was no significant increase in the 1-year survival rate. In both cases, adding a drug led to increased toxic effects.
These results should be reassuring to doctors, as current clinical practice in treating advanced NSCLC generally includes double-agent chemotherapy, which performed best in the trials surveyed. However, in an accompanying editorial, Drs. Athanassios Argiris and Joan Schiller of Northwestern University and the University of Wisconsin, respectively, point out that two-drug therapy regimens help only 35 to 40 percent of patients live a year or longer. They write that the future of NSCLC research lies in the continued development of targeted therapies.
Magnetic resonance imaging (MRI) was found to be more effective than mammography in the detection of breast cancer tumors in high-risk women, according to an article published in July 29 New England Journal of Medicine. Dr. Mieke Kriege and colleagues, in a Dutch Health Insurance Council-funded study, investigated whether MRI screening could detect breast cancer earlier than standard mammography screening in women genetically predisposed to breast cancer.
MRI provides information that is not obtainable through mammograms, but it is costly and unproven in certain populations.
A total of 1,909 women were enrolled in the Dutch study, where the median follow-up time was approximately 3 years. The researchers stated that "the overall discriminating capacity of MRI was significantly better than that of mammography." MRI screening was found to be a better method for high-risk women due to its capacity to detect small-scale tumors. Although the MRI was found to be more sensitive than mammography screening, scientists reported that caution must be used due to the lower specificity of MRI than mammography. This finding could lead to more uncertain screening results, requiring follow-up visits.