WSJ Article: Celebrex and Polyps

[Guest guest]

This article was in today's WSJ and mentions that Pfizer is studying

tthe use of Celebrex as a way to reduce colon polyps. Slightly

relevant to discussion here.

/Avi

ps: I've never been to Alaska.

***

Taking Pills to Prevent Cancer

Controversial Approach Targets

Healthy but At-Risk Patients

By AMY DOCKSER MARCUS

Staff Reporter of THE WALL STREET JOURNAL

At the age of 61, Ullman has never had a major health problem.

But for the past three years, she has been taking the drug Celebrex

in hope that it will lower her risk of getting colon cancer.

" I feel healthy now, but I want to find a way to prevent getting

cancer, " says Ms. Ullman, a travel consultant in Manhattan. " Wouldn't

it be great if a simple drug could do it? "

A quiet but important shift is taking place in the way physicians,

and their patients, think about cancer. For the past 30 years, the

focus has been on cure, with the pharmaceutical industry and federal

government pouring billions of dollars into the quest to develop

drugs to combat tumors. While that effort continues of course, an

increasing number of doctors and medical researchers are now

searching for drugs that will prevent or delay the onset of cancer in

the first place.

" You don't wake up one day out of the blue with cancer -- there is an

underlying disease process, " says Dannenberg, co-director of

cancer prevention at New York-Presbyterian Hospital in Manhattan. " We

need to focus more on stopping that process before it becomes cancer. "

Two key developments are making it easier to determine who should try

preventive cancer drugs: growing scientific evidence of a genetic

link to cancer and a deepening awareness that many cancers start out

years earlier as premalignant lesions.

In all, more than 50 clinical trials are under way testing compounds

and drugs to prevent cancer. Most are still recruiting patients. Some

doctors aren't waiting for definitive research results and are

already prescribing these drugs for high-risk patients. Just Monday,

the Food and Drug Administration approved a drug called Photofrin for

use in killing abnormal and possibly precancerous cells in patients

with Barrett's esophagus, an ailment related to acid reflux.

Ms. Ullman is part of a trial studying Pfizer Inc.'s Celebrex , a

nonsteroidal, anti-inflammatory drug used to treat arthritis. It has

already been shown to reduce precancerous polyps in patients with a

rare genetic syndrome that causes colorectal cancer. Now studies are

evaluating whether it will also help protect against the formation of

these polyps in average individuals. Oncologists are also studying

Celebrex to see if it can help repair lung damage from cigarette

smoking.

Other drugs that have sparked interest among researchers include

raloxifene, an osteoporosis drug marketed by Eli Lilly & Co. under

the brand name Evista, for breast-cancer prevention, and finasteride -

- sold as Proscar -- for prostate-cancer prevention. Merck & Co.,

which makes Proscar, said it plans to ask the FDA to approve the drug

for use in cancer prevention.

The concept behind chemoprevention -- using drugs and compounds to

delay, reverse or prevent disease -- is best known in the field of

preventing heart disease. " We accept the idea of taking medicine to

control our cholesterol and lower our blood pressure to help prevent

getting a heart attack, " says Waun Ki Hong, head of the division of

cancer medicine at the University of Texas M.D. Cancer

Center in Houston. " We can control the process of cancer development

with drugs too. "

Beyond Vitamins

Previous efforts, involving vitamins and aspirin, provide some reason

for optimism about the potential for drugs to stave off cancer.

Earlier this year, a study demonstrated that low doses of aspirin can

prevent precancerous polyps in people with a familial history of

colorectal cancer. A huge study is under way trying to determine

whether selenium and vitamin E prevent prostate cancer.

Growing numbers of drugs are being tested to see if they can help

prevent cancer but all of them have side effects.

But prescribing drugs to prevent cancer is controversial. That is

partly because it is harder to pinpoint who would most clearly

benefit from them -- and consequently more difficult to weigh the

potential risks of taking the medicine for years on end. " There is

currently no marker for cancer risk equivalent to high cholesterol, "

says New York-Presbyterian's Dr. Dannenberg.

Chemoprevention requires generally healthy people to take drugs or

compounds to prevent something that might, or might not, happen in

the distant future. Consequently, oncologists say it's usually worth

discussing only for people with a family history of cancer or with

other high-risk factors.

" The risk-benefit analysis is different for preventing cancer than

for treating cancer, " says Scardino, chairman of the department

of urology at Memorial Sloan-Kettering Cancer Center in New York.

Like all drugs, the medicines being studied for cancer prevention

have potential side effects, some of them serious. Raloxifene has

caused hot flashes and leg cramps and, in some rare cases, blood

clots in the veins. Celebrex can cause diarrhea. Even aspirin has

caused bleeding and an increased risk of stroke in some people.

Dr. Scardino points to the recent finasteride trial for preventing

prostate cancer to illustrate some of the issues that remain at stake

for the field of cancer prevention in general. While the drug did

clearly reduce the risk of getting prostate cancer, those taking it

reported decreases in sexual potency and libido. More worrisome:

There appeared to be an increased risk of high-grade prostate cancer

in those men who took the drug and did get cancer. Doctors who worked

on the trial say more research is needed to explain why this may have

happened.

Dr. Scardino questions whether it makes sense to put patients on

drugs that might prevent " cancers unlikely to pose a threat to their

lives if by taking the drug they are going to increase their risk of

getting an aggressive cancer that really will pose a risk to their

lives? " Answering that question still depends highly on an

individual's particular risks and priorities, something to be

determined in consultation with a doctor.

The risk of side effects is one reason that cancer-prevention efforts

have traditionally focused on dietary and lifestyle changes rather

than drugs. People are urged to quit smoking. They are encouraged to

exercise, eat a diet rich in fruits and vegetables, and, after a

certain age, to get regular screening exams such as mammograms or

colonoscopies. But for some people -- particularly those who are

genetically predisposed to get cancer -- this may not be enough to

stop tumors.

A Cautionary Tale

Still, some previous efforts at chemoprevention serve as cautionary

tales. Several years back beta-carotene seemed to show promise in

reducing the risk of lung cancer. But trials of men who were heavy

smokers showed it not only didn't prevent lung cancer, the people

taking beta-carotene actually got cancer at a higher rate than those

on the placebo.

In a landmark study published last year, a task force of the American

Association for Cancer Research concluded that many cancers start out

as premalignant lesions that over time develop into cancer. Many

oncologists have argued that by treating these lesions with drugs,

the process by which they eventually become cancer can be stopped or

delayed.

Finding these lesions is not as easy as measuring high cholesterol or

high blood pressure, though. Some, such as skin lesions, can be

fairly easily detected. Dentists spot such lesions in a patient's

mouth during routine checkups. Others will turn up during regular

screenings, like a colonoscopy.

But an invasive biopsy is often required to detect a precancerous

lesion. Sending every man for a prostate biopsy or every smoker for a

lung biopsy is not as practical as measuring someone's blood pressure

or doing a blood test during a routine annual physical.

But the recognition that there is now a way to flag who might be at

higher risk to someday get cancer marks an important step in finding

ways to prevent the disease and in setting up trials to test various

compounds. Many oncologists say that precancer will increasingly be a

focus of treatment efforts, particularly as the population ages and

starts doing regular screening exams that can turn up precancerous

lesions and as imaging technology gets more sensitive and can detect

such lesions more easily.

Several years ago, Comens, now 80, learned he had

precancerous lesions on his vocal chords. His doctor at M.D.

put him on high doses of a vitamin A derivative that caused his body

to swell and his skin to peel off in layers. " I peeled everywhere

from head to toe, " says Dr. Comens, who still practices medicine in

St. Louis. " It was very unpleasant. " But Dr. Comens says the lesions

went away and haven't returned, and that he was willing to suffer the

side effects for a chance to reverse a process that ultimately could

have cost him his voice or his life.

Write to Amy Dockser Marcus at amy.marcus@...

Updated August 5, 2003