In his lab at Weill Cornell Medical College, Dr. Andrew Dannenberg studies Celebrex, one of two hugely popular arthritis pain drugs. But his interest is different: Can its main ingredient, COX-2, fight cancer?
The answer is yes. Studies show that the COX-2 inhibitor in Celebrex reduces growth of precancerous polyps in a rare form of colon cancer so well that the pills are now approved by the Food and Drug Administration for that purpose.
“That medications may have secondary benefits is underappreciated by many health-care providers as well as patients,” said Dannenberg, who heads cancer prevention at Weill Cornell Medical Center.
But not always. In some cases, the secondary benefits overtake a drug’s original primary one.
For example, sildenafil citrate was supposed to treat high blood pressure. “And it didn’t work that well,” said Bronx cardiologist Dr. Jonathan Bradlow. But further investigation ? driven by men in the hypertension trial, who didn’t want to give up their samples ? led to Pfizer’s famously best-selling drug for erectile dysfunction, Viagra.
Rogaine was another hypertensive agent, developed at New York University.
“People noticed it grew hair in funny places,” said Dr. Bruce Cronstein, the head clinical pharmacologist at NYU’s School of Medicine. “But then a dermatologist said, ?Gee, maybe if you rub it on your head if you are bald?’ and they made it into a topical [liquid], and it’s Rogaine.”
Even as pill-takers worry about dangerous side effects ? including the millions of women who have been taking the now doubtful hormone replacement therapy ? doctors are finding unexpected benefits in dozens of medications.
Many prescribe them “off-label,” for purposes not approved by the FDA.
Variety of uses
For example, Botox, recently approved to quell forehead wrinkles, has been used off-label to smooth brows since it was approved in 1989 to treat facial tics and crossed eyes.
Knowledge about off-label benefits can help doctors choose between one medication and another depending on a patient’s risk factors for other maladies.
“Given a patient’s personal and family history, it can have an impact on decision-making when doctors prescribe,” Dannenberg said.
The potential is vast.
Statins, the powerful cholesterol-lowering drugs that are revolutionizing cardiac care, are being studied as potential treatments for osteoporosis ? bone loss ? Alzheimer’s disease and cancer.
Some diabetes drugs not only lower blood sugar but seem to provide extra cardiovascular benefits, says Dr. David Bloomgarden, endocrinologist and spokesman for the American Diabetes Association.
Antidepressants that soothe the blues might, depending on the drug, ease obsessive-compulsive and traumatic-stress disorders, boost sexual response, treat physical pain and even manage certain phobias.
A cancer drug, methotrexate, has become ? in small doses ? “the gold standard” for treating wickedly painful rheumatoid arthritis, Cronstein said.
More than 100 trials are underway with Celebrex, studying how it might fight an array of cancers ? breast, bladder, esophageal, skin and head and neck.
“We have promising preliminary results that select COX-2 inhibitors may be useful in the treatment of lung cancer,” Dannenberg said.
From such serendipitous benefits, researchers can learn how disease takes form. For example, people with rheumatoid arthritis have less colon cancer, “and they are all taking nonsteroidal anti-inflammatory drugs,” Cronstein said.
So powerful are anti-inflammatories that they have made doctors reassess the role of inflammation in heart disease and cancer ? exciting new research that seems to be reshaping the way doctors understand and manage killer maladies.
Side benefits come to light by accident, popular demand, observation and lab study. The first wonder drug was aspirin ? acetylsalicylic acid ? used for aches and fever since Hippocrates in 400 B.C., when users might get relief chewing on willow bark that contains aspirin in its natural form, salicin.
In 1897, a German scientist put it in a powder, and Bayer aspirin was born. Fifty years later, a general practitioner in the American Midwest noticed that 400 men to whom he’d given aspirin hadn’t had any heart attacks.
Word got around, and studies were done. Today, aspirin is approved for preventing first and second heart attacks, stroke and transient ischemic attacks, or TIAs, the “ministrokes” that can precede brain attacks.
It’s also the drug to take while having a heart attack, to limit damage, and 50 ongoing studies are exploring other applications, said Dr. Laureen MacEachern, Bayer’s head of clinical research.
Scientists also “leverage the inherent mechanism of the drug and look at other applications for it,” said Dr. Gabe Leung, Pharmacia’s head of cancer research. His people knew that cancer cells overproduce the COX-2 enzyme. Could a drug that inhibits the growth of COX-2 help fight cancer?
Subsequent research, including Dannenberg’s, led to the approval of Celebrex for familial adenomatous polyposis, or FAP, a rare killer that unchecked will cause colon cancer by age 50 in 100% of those who carry the wrong gene.
Already, the drug and its sister COX-2, Merck’s Vioxx, also reduce fever, and small studies show that both might have a role in treating a certain kind of bladder cancer and Alzheimer’s disease.
All drugs carry some risk, Leung said. But sometimes a negative side effect in one medical context becomes a problem-solver in another. “It is wonderful,” he said.
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