Drugs to deter some cancers are largely ignored, experts say

 Many do not think twice about taking medicines to prevent heart disease and stroke. But cancer is different. Much of what Americans do in the name of warding off cancer has not been shown to matter, and some things are actually harmful. Yet the few medicines proved to deter cancer are widely ignored.

 Take prostate cancer, the second-most commonly diagnosed cancer in the United States, surpassed only by easily treated skin cancers. More than 192,000 cases of it will be diagnosed this year, and more than 27,000 men will die from it.

 And, it turns out, there is a way to prevent many cases of prostate cancer. A large and rigorous study found that a generic drug, finasteride, costing about $2 a day, could prevent as many as 50,000 cases each year. Another study found that finasteride’s close cousin, dutasteride, about $3.50 a day, has the same effect.

 Nevertheless, researchers say, the drugs that work are largely ignored. And supplements that have been shown to be not just ineffective but possibly harmful are taken by men hoping to protect themselves from prostate cancer.

 As the nation’s war on cancer continues, with little change in the overall cancer mortality rate, many experts on cancer and public health say more attention should be paid to prevention.

 But prevention has proved more difficult than many imagined. It has been devilishly difficult to show conclusively that something simple like eating more fruits and vegetables or exercising regularly helps. And, as the response to the prostate drugs shows, people are not enthusiastic about taking anti-cancer pills, or are worried about side effects or not really convinced the drugs work. Others are just unaware of them.

 And prostate cancer is not unique. Scientists have what they consider definitive evidence that two drugs can cut the risk of breast cancer in half. Women and doctors have pretty much ignored the findings.

 Companies have taken note, saying that it makes little economic sense to spend decades developing drugs to prevent cancer. The better business plan seems to be looking for drugs to treat cancer. That is a sobering lesson, said Dr. Ian M. Thompson Jr., chairman of the urology department at the University of Texas Health Science Center in San Antonio.

 “A scientific discovery that is very clear-cut and that is not implemented by the public is a tragedy,” he said.

 Dr. Peter Greenwald knows the dashed hopes of cancer prevention research firsthand. As far back as 1981, when he arrived at the National Cancer Institute to direct “cancer prevention and control,” Greenwald began thinking about testing whether simple measures, like vitamin supplements, could prevent common cancers.

 He focused on what looked like it could be a sure thing — beta carotene, found in orange fruits and vegetables as well as in green leafy vegetables.

 The body converts beta carotene to vitamin A, which can prevent cancer in rats. People eating the most fruits and vegetables had less cancer. And the more beta carotene in a person’s blood, the lower the cancer risk. Lung cancer seemed particularly vulnerable to beta carotene’s effects, particularly in smokers and former smokers.

 What was needed was cause-and-effect evidence, studies showing that if people bolstered their beta carotene and vitamin A levels, they would be protected from cancer. The cancer institute decided to take it on with two large studies.

 But not only did the supplements not work, but there was evidence that beta carotene might actually increase cancer risk in smokers.

 Greenwald and his colleagues still held out hope for vitamins and minerals as cancer preventatives. So his group proposed the largest cancer prevention clinical trial ever tried, involving 35,000 men 50 and older. This time, the idea was that vitamin E and selenium might prevent prostate cancer.

 Once again, there was presumptive evidence. But this time it was harder to persuade scientists to go ahead. After the beta carotene and vitamin A studies, several other studies had also failed to find evidence that food components or special diets could prevent cancer.

 “By this time, a lot of people were very concerned,” said Dr. Scott M. Lippman, an oncologist at the University of Texas M.D. Anderson Cancer Center. He argued that the huge study had to be done. The supplements were being promoted for “prostate health,” and the evidence that they might actually work was tantalizing.

 The selenium and vitamin E study ended early. Once again, there was no protection from cancer, and there were hints the supplements might be causing cancer. Once again, the great hope turned into a stunning disappointment.

 In 1990, Dr. Victor G. Vogel was at M.D. Anderson and had high hopes of changing the world. It just may be possible, he thought, to prevent many cases of breast cancer in women at high risk, a group that includes every woman over age 60, the time when the risk takes a sharp turn upward.

 Vogel was to be an investigator in a huge study of 13,000 women that seemed to have everything going for it. It would test a drug, tamoxifen, an estrogen-blocker widely used to treat women with breast cancer. The studies showing the drug’s effects in breast cancer patients, though, had an unexpected bonus. It looked as if tamoxifen was also preventing new cancers in the opposite breast.

 “By the time we got to 1990, there was just a huge amount of data,” Vogel said. The drug’s risks were well-established and seemed well worth taking if the benefit was cutting cancer in half among women at high risk. Most side effects, like hot flashes, were temporary. But there also was a risk of blood clots similar to that conferred by birth control pills or estrogen used to relieve symptoms of menopause. And there were about two additional cases of uterine cancer per 1,000 women per year.

 By 1998, the results were in. Tamoxifen cut the breast cancer rate in half. Similar studies in Britain and Italy, also involving high-risk women who had not had breast cancer, came to similar conclusions. And women did not have to take the drug for a lifetime — they needed just five years of therapy.

 Vogel was ecstatic.

 “If I had told you in 1990 that in 10 years I would have a pill that would cut the risk of breast cancer in half, you wouldn’t have believed me,” he said.

 But, he said, to his shock, “the world said, ‘So what?’

 “We were met with shoulder shrugs and harrumphs,” Vogel said. Sales of tamoxifen, worldwide, “didn’t budge.”

 Maybe, Vogel thought, the problem was that internists and gynecologists were not comfortable prescribing a drug used to treat cancer patients. Then, in 1999, he had a chance to do another breast cancer prevention trial, this time of an osteoporosis drug, raloxifene, or Evista, which did not have the cancer drug taint. It was to be compared with tamoxifen.

 The $110 million study, involving 19,000 women, ended in 2006. The two drugs were found to be equally effective in preventing breast cancer, but with raloxifene there was no excess uterine cancer and the clotting risk was 30 percent less.

 “It was a spectacular clinical trial,” Vogel said. But, he added, “Once again, the world met the result with a shrug and a harrumph.

 “Those were your tax dollars and mine,” he added. “You can’t do too many $110 million studies.”

 He cannot understand why no one cares, but some doctors say they see a number of problems. It is usually not the cost; tamoxifen is about 30 cents a day and raloxifene $3.30 a day. It is doctors’ practices and women’s concerns.

 Most doctors, said Dr. Therese B. Bevers, medical director of the Cancer Prevention Center at M.D. Anderson, do not take the first step — calculating a woman’s lifetime risk of getting breast cancer — in part because that can lead to the next step, spending an hour or so discussing cancer risk and drug risks and benefits.

 Bevers suggests the drugs for women whose lifetime odds exceeds 20 percent. That could include, for example, a 55-year-old woman who began menstruating early (increasing the risk), had her first child late (again increasing the risk), and whose mother and sister got breast cancer. About half the time, though, women with that kind of risk turn down the drugs, Bevers said. “The Number 1 reason I hear is, ‘Oh, I just don’t like to take medications,’ ” she added.

 Others, like Cecilia Anderson, who is 57 and lives in Houston, worry about side effects. “I felt like my quality of life was in question,” she said. “I am busy, I am out there. I totally love my life and don’t want it to be compromised.” Her lifetime risk of breast cancer is 20.5 percent, compared with an average risk of 9.8 percent for a woman her age.

 Anderson declined the drugs. “I live a different lifestyle,” she said. “I eat organic foods, I exercise. Through all of that comes a spiritual element as well. Mind, body and spirit are all connected.”

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