Aspirin Puts It’s Money where It’s Mouth Is
One of the very most fascinating prospects in cancer prevention is an economical and very familiar drug: aspirin.
In fact, the U.S. Preventive Services Task Force-Exit Disclaimer is working on recommendations for the use of aspirin to reduce cancer risk.
Aspirin is broadly used.
A staggeringly large number of people take it daily to reduce the danger of stroke or heart attack. And many studies over the last two decades have suggested that taking aspirin regularly may greatly lower a person’s risk.
In 2011, for instance, a meta-analysis of eight randomized clinical trials that compared the threat of cancer death among participants who took daily aspirin for 4 years or more and people who took no aspirin found that, overall, aspirin use lowered the threat of dying from cancer by about 20%.
By viewing data from each participant in these trials, the researchers, headed by Peter Rothwell, M.D., Ph.D., FRCP, of the University of Oxford, revealed that this risk reduction was due mainly to fewer cancer deaths among participants who took aspirin for at least 5 years.
The largest fall in risk was for gastrointestinal cancers, particularly colorectal cancer. The research also showed more modest risk decreases for several other common cancers, including lung and prostate.
The research findings on aspirin aren’t clear cut.
Not every study of cancer and aspirin has revealed that it reduces the possibility of developing or dying from cancer.
But more conclusive evidence could be to the horizon.
Specifically, researchers in search of answers are looking to a number of large clinical trials which have been launched to test whether aspirin reduces the risk of cancer incidence.
3 Questions and Answers to CAPP2
The mounting evidence of aspirin’s strong anticancer effect for many malignancies is difficult to dismiss, said Dr. Rothwell, who took charge of recent studies ultimately reinforcing the case for aspirin. The newer studies contain a 2012 meta-analysis, which linked a decreased risk of developing cancer that is metastatic and aspirin.
“I do believe there is a role for using [NSAIDs] at a subtherapeutic level for various types of tumors,” Rothwell said.
Dr. Rothwell isn’t alone in his opinion.
A decade ago, Dr. Harris published findings from a prospective observational study of participants in the Women’s Health Initiative (WHI), which found that women who took aspirin or ibuprofen at least twice a week for 5 years or more had a reduced risk of breast cancer.
But that sentiment is not universal. John Baron, M.D., M.S., M.Sc., of the University of North Carolina Lineberger Cancer Center, concurred that there is strong evidence that aspirin reduces the risks of particular cancers. But, he noted, it is still inadequate.
“More formal study is needed to nail down [aspirin’s] risks and benefits,” Dr. Baron said.
How Does Aspirin Work against Cancer?
Researchers think that aspirin may work, at least in part, by blocking the activity of COX 2 and COX-1 enzymes, lynchpins in the body’s inflammatory reaction. Inflammation is a normal response to tissue injury or disease which helps the injured tissue to clear the infection or to mend.
In chronic inflammation, the inflammatory process doesn’t end when it should. Over time, long-term inflammation can cause changes, including the formation of DNA mutations and new blood vessels, which may promote tumor development and growing.
Aspirin: Reasons for Caution
A lot of the reluctance expressed by Dr. Baron and others stems in part from the fact that few randomized clinical trials specifically designed to examine the effect of aspirin on consequences like cancer risk and mortality have been carried out.
“Only when you do a randomized clinical trial do you get the complete picture of what’s going on,” described Asad Umar, D.V.M., Ph.D., of NCI’s Division of Cancer Prevention.
Clinical trials may also highlight potential security issues that are not always clear in trials or observational studies requiring different patient populations. Dr. Umar cited the experience with a different NSAID, celecoxib (Celebrex– registered company).
Evidence of potential adverse cardiac effects from routine long-term treatment with celecoxib only emerged when it was examined with longer patient follow-up, such as the NCI-financed Adenoma Prevention in large trials.
Improvements have been made on this front. Consider, for instance, a large randomized placebo-controlled trial conducted in the United Kingdom called CAPP2.
A study conducted on people with Lynch syndrome who took high-dose aspirin (600 milligrams) for at least 2 years, had a considerably lower prevalence of colorectal cancer than participants who took a placebo.
The accessible data on aspirin’s security are somewhat reassuring, Dr. Rothwell noted. In the trials contained in the 2011 meta-analysis, for instance, there were more fatal bleeding events among participants who took a placebo than among people who took aspirin (60 versus 40 events), even though the risk of non-fatal bleeding increased.
And, in the CAPP2 trial, the amount of cases of gastrointestinal bleeding in the aspirin group and placebo groups were quite similar (11 versus 9 cases), according to the study’s lead author, Dr. John Burn of Newcastle University.
Aspirin: Filling in the Blanks
According to several researchers, several important questions have to be answered before aspirin may be looked at for use as a cancer prevention measure, this includes what dose provides the most protection against cancer and the lowest risk of serious side effects.
- Who’s most prone to benefit from aspirin use
- Which cancers does aspirin protect against
- How long after stopping aspirin does its anticancer protective effect last
As for which cancers aspirin protects against, several studies have indicated that those that have particular attributes that were molecular may be specifically prevented by it.
Another study by researchers in the Dana-Farber Cancer Institute implied that aspirin use prevents the growth of cancers that possess the regular version of a gene called BRAF, which was implicated as a vital driver of many cancers, although not cancers with a mutated type of the gene.
And several of the same researchers discovered that death was only reduced by aspirin use after having a colorectal cancer diagnosis from cancer if a patient’s tumor produced large amounts of COX-2, an enzyme involved in inflammation.
While the results make biological sense.
“These findings must be replicated before we can make sure of the same researchers,” Dr. Umar cautioned.
Meanwhile, continuing studies should offer better comprehension of how aspirin (and other NSAIDs) shields against cancer and can aid the development of safer, more potent forms of the drugs.
Dipak Panigrahy, M.D., and Charles N. Serhan, Ph.D., of Harvard Medical School are inquiring how specific types of resolvins (anti-inflammatory molecules that are created in the body when aspirin socializes with omega-3 fatty acids) block tumor growth and metastasis.
His research is financed through NCI’s Provocative Questions (PQ) program. Building on earlier NSAIDs research, another PQ-financed team, led by Laurie Hudson, Ph.D., and Angela Wandinger-Ness, Ph.D., of the University of New Mexico Cancer Center, are examining how NSAIDs that work otherwise than aspirin can affect the development and spread of cancer cells.
A current case-control study, for example, found that use of low-dose aspirin following a colorectal cancer analysis did not enhance cancer survival.
Dose is certainly a critical question, said Dr. Umar.
“As with all drugs, there are potential risks and benefits with aspirin,” Dr. Umar said, he continued on to say.
“And anybody considering taking aspirin on a regular basis, should talk to their primary care physician first.”
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