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Tuesday, August 11, 2009
Benefit seen in COX-2 expressing tumors, follow-up needed before application to patient care
Postdiagnosis aspirin use reduces risk of dying from colorectal cancer
Regular use of aspirin after colorectal cancer diagnosis may reduce the risk of cancer death, report investigators from Massachusetts General Hospital (MGH), Dana-Farber Cancer Institute and Brigham and Women's Hospital. In the August 12 issue of the Journal of the American Medical Association, the study's authors also find that the aspirin-associated survival advantage was seen primarily in patients with tumors expressing the COX-2 enzyme, a characteristic of two-thirds of colorectal cancers.
"While previous studies by our group and others showed that aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of developing colorectal cancer, this study is the among the first to show that aspirin can also improve survival in patients who have already been diagnosed with colorectal cancers. Moreover, the benefit appeared to be especially strong among patients with cancers that express COX-2," says Andrew Chan, MD, MPH, of the MGH Gastrointestinal Unit, the study's lead author. "This is an important first step toward developing targeted approaches to improving patient outcomes."
Many previous studies have shown that regular use of aspirin and other non-steroidal anti-inflammatory drugs reduces the risk of developing colorectal cancer. In 2007, the same MGH/DFCI research team found that the benefit only applied to tumors overexpressing COX-2, an enzyme believed to drive tumor growth and known to be inhibited by aspirin and related drugs. To test their hypotheses that aspirin would also improve the survival of patients diagnosed with colorectal cancer, again through its inhibition of COX-2, the researchers compiled data from two ongoing prospective research studies - the Nurses Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Both studies gather comprehensive health information on their participants every two years; data are then analyzed for associations between factors such as medication use and the incidence of several diseases.
The current study focused on 1,279 study participants who were diagnosed with stage 1, 2 or 3 colorectal cancer during their participation in the studies for whom data was available on aspirin use before and after diagnosis. Tumor samples available from 459 participants were analyzed for the expression of COX-2. Study results indicated that patients who regularly took aspirin after their diagnosis - defined as those taking a 324 mg tablet at least twice a week - had a nearly 30 percent lower risk of dying of colorectal cancer during an average of 11 years after diagnosis than did non-aspirin users. The benefit was especially strong among patients who began using aspirin after diagnosis. In contrast, patients who were aspirin users before diagnosis did not appear to benefit as much from continuing aspirin use after diagnosis. As expected, the survival benefit appeared restricted to patients with COX-2-positive tumors.
"We believe our results could lead to improvements in the therapy of patient with colon cancer," says Charles Fuchs, MD, MPH, of Dana-Farber, the study's senior author. "We're now following up this observational study with a randomized trial to evaluate adding the COX-2 inhibitor celecoxib - which is less likely to have the gastrointestinal side effects of aspirin - to standard chemotherapy."
Fuchs is an associate professor of Medicine at Harvard Medical School, where Chan is an assistant professor of Medicine. Study co-author Shuji Ogino, MD, PhD, is an HMS associate professor of Pathology at Brigham and Women's Hospital. The study was supported by grants from the National Cancer Institute and the Damon Runyon Cancer Research Foundation.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), a designated comprehensive cancer center by the National Cancer Institute.
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