Here's more on Evista:
By Jenifer Joseph
ABCNEWS.com
March 19 - Maybe you've seen the splashy ads for a hot new drug called Evista. Perhaps your doctor has already prescribed it for you, because you're one of the 18 million Americans at risk for osteoporosis, or brittle bone disease.
ÿÿÿÿ As the first entry in a new class of medications, Evista was launched with high hopes shortly after the Food and Drug Administration OK'd it last December, just six months after drugmaker Eli Lilly applied for approval.
ÿÿÿÿEvista is the brand name for raloxifene, a synthetic estrogen that was shown in clinical trials to protect post-menopausal women against osteoporosis-without the side effects of estrogen.
ÿÿÿÿIn February, doctors wrote 27,000 prescriptions for Evista, somewhat below the manufacturers' and business analysts' predictions.
ÿÿÿÿAccording to Dr. Samuel Epstein, a professor of environmental and public health at the University of Illinois in Chicago, that's 27,000 prescriptions too many.
ÿÿÿÿEpstein would like to see Evista pulled off the market altogether and cancer warnings sent to everyone taking the drug. His reasoning: In tests done by Eli Lilly, the drug was linked to ovarian tumors in mice and rats; low doses were associated with benign tumors, and high doses with malignant tumors. <Picture: Evista Ad>Ads for Evista have appeared in newspapers and magazines. (Eli Lilly)
ÿÿÿÿAs Epstein points out, the package insert that comes with Evista says that "the clinical relevance of these tumor findings is not known." In his view, that information gap may pose a serious problem for women who take Evista.
ÿÿÿÿ "It could be decades before ovarian cancer shows up in women," as opposed to rodents, Epstein says. "We shouldn't put 20 million women at risk." In addition, he says, "Lilly designed the study to prove overall safety, and when it turned out that it wasn't safe, they didn't disclose this to women."
Of Mice and Women
Not everyone agrees with Epstein, of course, including Eli Lilly. The drug did get FDA approval (though some on the agency's advisory committee voted against it), and at least one osteoporosis expert characterizes Epstein's claims as reckless.
ÿÿÿÿ"What he's saying is an outrage," says Dr. Ethel Siris, director of Columbia-Presbyterian Medical Center's osteoporosis program. "It's a mouse-specific phenomenon. There's no relevance to women."
ÿÿÿÿSiris, who was one of the physicians involved in the clinical trials for Evista, has not a smidgen of concern that her patients taking Evista will get ovarian cancer. After all, she says, "I don't see any mice in my practice."
ÿÿÿÿIn a way, Siris' remark perfectly summarizes the questions Epstein raises about Evista and ovarian-cancer risks. Will a drug that causes tumors in rodents necessarily have the same effect on women? And what exactly is the mechanism that produces ovarian tumors? Is it the same in rodents as it is in humans?
Rodents Are Different From You and Me
Eli Lilly's theory is this: Evista raises the levels of the luteinizing hormone (LH) that drives the ovaries to produce eggs, and any condition that raises LH levels in rats and mice will increase the chance that a tumor will form.
ÿÿÿÿ"That's been demonstrated before," says Lilly endocrinologist Dr. Leo Plouffe. However, Plouffe notes, the drug did not increase LH levels in post-menopausal women, and as a result, the women in the Evista trials didn't develop ovarian tumors in any significant numbers.
ÿÿÿÿThe problem with Eli Lilly's rodent theory, say cancer experts around the country, is that it's just that.
ÿÿÿÿ"We don't know what causes ovarian tumors," says Dr. Beth Karlan, director of Cedars-Sinai Medical Center's ovarian cancer program in Los Angeles. "It's just a theory that we don't know to be true."
No Easy Approval
That worries the people at the National Women's Health Network, a medical watchdog group.
ÿÿÿÿ"Unlike other cancers, we know very little about ovarian cancer," says executive director Cynthia Pearson. "So this is treacherous territory. We shouldn't rubber-stamp this drug if the risks have been discarded based on a theory that isn't accepted by everyone."
ÿÿÿÿIn fact, after a full day of detailed discussion about the drug's safety and efficacy, four members of the 12-person FDA advisory committee weren't willing to give that rubber-stamp.
ÿÿÿÿDr. Jose Cara of the Henry Ford Hospital was one of those who turned it down, partly because of the ovarian cancer risk, and partly because of the fact that, while the drug has been shown to increase bone density, studies to determine whether it actually reduces bone fractures won't be completed for another six months. That, he says, will be the true test of the drug's worth.
ÿÿÿÿ"We're always faced with the difficulty of getting drugs approved quickly while trying to determine whether they're safe," Cara says. "We have to balance animal studies with clinical data, so it's a tough call."
ÿÿÿÿStill, Eli Lilly officials maintain, the most important fact about Evista's safety is that it has not been linked to ovarian tumors in the thousands of women who participated in the drug's clinical trials, which lasted for three years.
ÿÿÿÿ"The key issue is what's happening in women," says Dr. Willard Dere, Lilly's director of endocrine research. "We have carefully evaluated over 13,000 women, and there is no evidence at all that there an increase in ovarian cancer."
ÿÿÿÿOnly six women were found to have had cancer during the trials, which is actually a lower rate than what would normally show up in the general population.
ÿÿÿÿThat's certainly reassuring information for Evista takers-for now. Sometimes, once a drug hits the market and the population of people taking it expands, side effects and risks emerge that weren't obvious in the clinical trial phase. People like Samuel Epstein and Cynthia Pearson will be watching see if this happens with Evista.
Who Gets Ovarian Cancer and Why Ovarian cancer is relatively rare but serious. The lifetime risk that a woman will develop ovarian cancer is 1 in 70, and two-thirds of these women die from the disease, according to the National Cancer Institute. The average age of diagnosis is 61.
ÿÿÿÿOvarian cancer occurs when cells on the outer lining of the ovaries grow and divide uncontrollably. It can spread throughout the body, but is most likely to metastasize to abdominal organs.
ÿÿÿÿAccording to Dr. Steve Narod at the Center for Research in Women's Health at the University of Toronto, ovarian cancer has the highest heredity incidence of any cancer. When it comes to genetic ties, he says, "It's the only one we're sure of beyond any doubt."
ÿÿÿÿWomen who have the genetic <Picture> mutations BRCA-1 or BRCA-2 are at the greatest risk. Those with the BRCA-1 mutation have a 45 percent risk, and those with the BRCA-2 mutation have a 25 percent chance. Eleven percent of all ovarian cancers are due to these gene mutations.
ÿÿÿÿOther risk factors include the use of talcum powder in the vaginal area; ovarian-stimulating drugs used before in vitro fertilization; and not having children.
ÿÿÿÿHaving babies protects against the disease, says Narod. "The more you have, the better."
ÿÿÿÿFor women who carry one of the gene mutations, taking birth control pills can reduce their five-year risk by 50 percent. Tubal ligation and hysterectomy may also lower the risk in women with BRCA mutations. |
