(Press-News.org) CHICAGO – Adding the drug cetuximab to a regimen of drugs used for the treatment of patients following surgery for stage III colon cancer did not result in improved disease-free survival, according to a study in the April 4 issue of JAMA.
Patients who have surgery for removal of stage III colon cancer have a 50 percent chance of cure. Multiple trials have established the benefit of chemotherapy after surgery in reducing the recurrence risk. "Specifically, [the drugs] leucovorin, fluorouracil, and oxaliplatin (FOLFOX or slightly different method, FLOX) provides significant benefit in both disease-free and overall survival compared with the prior standard of fluorouracil and leucovorin," according to background information in the article.
In the setting of metastatic colorectal cancer, the drugs cetuximab and panitumumab, alone and in combination with chemotherapy, have provided additional benefit to that obtained with chemotherapy alone. "This benefit, however, is limited to patients with tumors expressing the wild-type [a strain used as a standard reference to compare any mutant derivatives] form of the gene KRAS as opposed to those with the mutated form of KRAS," the authors write.
Steven R. Alberts, M.D., of the Mayo Clinic, Rochester, M inn., and colleagues conducted a study to assess the potential benefit of cetuximab added to the modified sixth version of the FOLFOX regimen (mFOLFOX6) in patients with resected stage III wild-type KRAS colon cancer. Patient enrollment began February 2004 and was permanently halted on November 25, 2009, after the second planned interim analysis demonstrated a low probability that disease-free survival of the cetuximab group would surpass that of the mFOLFOX6-only group. A total of 2,686 patients comprised this analysis cohort (1,863 patients with wild-type KRAS, 717 patients with mutated KRAS, and 106 patients with indeterminate KRAS). The primary randomized comparison was 12 biweekly cycles of mFOLFOX6 with and without cetuximab. Median follow-up was 28 months.
The researchers found that the trial demonstrated no benefit when adding cetuximab. Three-year disease-free survival for mFOLFOX6 alone was 74.6 percent vs. 71.5 percent with the addition of cetuximab in patients with wild-type KRAS, and 67.1 percent vs. 65.0 percent in patients with mutated KRAS, with no evidence of benefit in any individual subgroup. Also, both time-to-recurrence and overall survival were not significantly different between treatment groups.
"Among all patients, grade 3 or higher adverse events (72.5 percent vs. 52.3 percent) and failure to complete 12 cycles (33 percent vs. 23 percent) were significantly higher with cetuximab," the authors write. "Increased toxicity and greater detrimental differences in all outcomes were observed in patients aged 70 years or older."
The researchers add that the reasons for the lack of benefit of mFOLFOX6 with cetuximab in the adjuvant setting remain unclear.
"In this randomized phase 3 trial for patients with resected stage III colon cancer expressing wild-type KRAS mutations, the addition of cetuximab to mFOLFOX6 did not improve disease-free or overall survival in contradistinction to the original study of cetuximab combined with FOLFOX in metastatic colorectal cancer," the authors write. "New approaches are needed to identify drugs that may be of benefit in adjuvant therapy, because as shown in our trial promising activity in the metastatic setting did not translate into adjuvant therapy benefit and underscores the importance of performing clinical trials."
(JAMA. 2012;307[13]:1383-1393. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Antitumor Activity in Metastatic Disease Does Not Predict Efficacy in the Adjuvant Setting
In an accompanying editorial, Neil H. Segal, M.D., Ph.D., and Leonard B. Saltz, M.D., of Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, write that although the negative results of this trial are surprising, this pattern has been observed before.
"The inescapable conclusion is that efficacy in the metastatic setting does not reliably predict efficacy in the adjuvant setting. The role of adjuvant chemotherapy does not involve treating the tumor that the surgeon has removed, but rather attempts to eradicate whatever occult micrometastatic disease may still be present after surgery. If there are no micrometastases, surgery is curative and adjuvant chemotherapy is unnecessary. If micrometastases are present, the long-term health of the patient will depend on whether the chemotherapy can destroy all remaining micrometastases."
(JAMA. 2012;307[13]:1431-1432. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
###
To contact Steven R. Alberts, M.D., call Joe Dangor at 507-284-5005 or email dangor.yusuf@mayo.edu. To contact editorial co-author Leonard B. Saltz, M.D., call Courtney Nowak at 212-639-3573 or email Denicolc@mskcc.org.
END
CHICAGO – In an analysis of a cohort that included nearly one million patients who had visited an ophthalmologist, patients who were taking oral fluoroquinolones had a higher risk of developing a retinal detachment, a serious eye condition, compared with nonusers, although the absolute risk was small, according to a study in the April 4 issue of JAMA.
"Fluoroquinolones are one of the most commonly prescribed classes of antibiotics. Their broad-spectrum antibacterial coverage and high-tissue distribution provide potency for a wide variety of community-acquired infections," ...
CHICAGO --The feasibility of selecting treatment based on individual molecular characteristics was demonstrated in a first-of-its kind pancreatic cancer clinical trial reported today by the Translational Genomics Research Institute (TGen) and the Virginia G. Piper Cancer Center at Scottsdale Healthcare.
The findings were announced during the American Association for Cancer Research (AACR) Annual Meeting 2012, March 31-April 4, in Chicago.
"The most important finding is that this approach is feasible and we are encouraged by preliminary evidence that this approach may ...
Johns Hopkins investigators are testing a way to use drugs that target a cholesterol pathway to enhance the cancer-killing potential of standard chemotherapy drugs. Their tests, in mouse models of pancreatic cancer, may yield new and more effective combinations of current and possibly new anti-cancer drugs.
Besides their deadly consequences, pancreatic cancer and heart disease share a connection with genetic pathways that control cholesterol and a cell signaling system known as the Hedgehog pathway. (The name refers to the shape of its mutated protein in fruit flies, ...
In a research article published April 3 in the online, open-access journal PLoS Biology, Prof. Sylvia Cremer and colleagues at the Institute of Science and Technology, Austria show how micro-infections promote social vaccination in ant societies. Like crowded megacities, ant colonies face a high risk of disease outbreaks. These are kept in check by the ants' social immune system—a set of collective hygienic behaviours and adaptive changes in interaction frequencies that acts in conjunction with the physiological, innate immune system of colony members. Prof. Cremer and ...
Top executives at Anago Cleaning Systems hosted its 2012 annual conference for their Master Franchisees in an effort to celebrate major growth and successes in 2011, and prepare for aggressive expansion and improvement throughout each territory and the nation. New and existing Master Franchisees alike attended the two-day show that was held on March 5-6, 2012 in Orlando, Florida.
The convention kicked off with opening remarks from Anago Cleaning Systems Founder, David Povlitz.
Mr. Povlitz reiterated that the vision, mission, and values of the company he founded in ...
An international team of scientists has created an innovative tool for teaching the fundamentals of epidemiology—the science of how infectious diseases move through a population.
The team teaches a workshop annually in South Africa that helps epidemiologists improve the mathematical models they use to study outbreaks of diseases like cholera, AIDS and malaria. Led by Steve Bellan from the University of California at Berkeley, the team created a new game as a teaching aid for the workshop. The exercise, which has proven extremely effective in demonstrating concepts in ...
Genetic mutations in cancer cells can lead to resistance to treatment, thereby potentially resulting in relapse. However, a new article, published April 3 in the magazine section of the online, open-access journal PLoS Biology, suggests that the converse may also happen. Steven Frank from the University of California, Irvine, and Marsha Rosner from the University of Chicago, propose that it may often be the case that a few cells become resistant before any genetic change, and then later acquire the genes to stabilize that resistance.
Why does it matter whether resistance ...
CAL Business Solutions, a Connecticut based Microsoft Dynamics GP partner, today announced that it will host the first ever New England SalesPad user group workshop. Companies using Microsoft Dynamics GP with SalesPad, an add on product for the distribution industry, will have the opportunity to come together to see new features, share ideas, network with their peers and provide input on future product developments.
The user group will be held at the Crowne Plaza hotel in Cromwell, Connecticut from 8:00-11:30am on Monday May 7th. Topics on the agenda include advanced ...
New evidence points to a hormone that leaves muscles gobbling up sugar as if they can't get enough. That factor, which can be coaxed out of fat stem cells, could lead to a new treatment to lower blood sugar and improve metabolism, according to a report in the April issue of Cell Metabolism, a Cell Press publication.
This new fat-derived hormone would appear to be a useful alternative or add-on to insulin; it can do essentially the same job, sending glucose out of the bloodstream and into muscle.
"It's like you've opened the door and now the glucose can come in," said ...
Philadelphia, PA, April 3, 2012 – A new report published online today in the Journal of the Academy of Nutrition and Dietetics systematically reviews and updates the evidence underlying the recommendation in the Dietary Guidelines for Americans 2010 to consume a diet low in energy density (ED). The report addresses the growing body of evidence linking ED, or the number of calories in a given amount of food, and body weight in adults as well as children and adolescents. The systematic review concluded that there is strong and consistent evidence in adults showing that consuming ...
