Early, Unproven Findings Changing Doctors' Practice

Study finds many use experimental drugs too soon, potentially putting patients in danger

TUESDAY, March 14, 2006 (HealthDay News) -- Too many American doctors are jumping the gun when it comes to how they treat patients -- switching to new, largely unproven therapies on which there is only early, incomplete data.

That's the conclusion of a study in the March 15 issue of the Journal of the National Cancer Institute that discovered early findings presented at a national cancer conference rapidly changed the way doctors treated breast cancer -- even though the trial needed much more data and time to offer up conclusive results.

Luckily for American women, the completed study -- published years later in a medical journal -- ended up confirming the effectiveness of the drug Taxol against a specific type of breast malignancy.

But the authors of the new study warn that many other treatments -- for example, cox-2 painkillers or the lung cancer drug Iressa -- looked just as promising during the early days of trials, only to prove useless or even harmful as more complete data emerged over time.

"Our message is for the physicians in the community to be aware of the potential risks of adopting therapies too early, and also for physicians presenting early results at meetings to be aware of how dramatically practice can change, based on their presentations," said study author Dr. Sharon Giordano, an assistant professor of medicine in the department of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, in Houston.

The danger of this type of early hyping is very real: A Canadian study, published in the March 15 issue of the Journal of the American Medical Association, found that 41 percent of preliminary trial results presented as "highlights" at medical meetings ended up having more disappointing conclusions when final findings were published in medical journals later.

"When things are reported at scientific meetings, those are often preliminary results," noted Dr. Lisa Schwartz, co-director of the V.A. Outcomes Group and an associate professor of medicine at Dartmouth Medical School.

"That means that the study might not even be complete -- they are reporting on interim findings," said Schwartz, who co-authored a related JNCIeditorial. "So, we just don't know whether those results will hold up over time."

In the JNCI study, Giordano's group tracked changes in breast-cancer treatment after researchers announced preliminary findings on Taxol (paclitaxel) at the 1998 annual meeting of the American Society of Clinical Oncology (ASCO). The researchers presented early data suggesting that Taxol improved survival for women with breast cancers that had spread to the nearby lymph nodes, if given after lumpectomy/mastectomy as an "adjuvant" therapy.

The study, although incomplete, was widely publicized by major media, with stories in The New York Times, the Wall Street Journal and elsewhere trumpeting the findings.

"We found that very, very quickly after the meeting, physicians began prescribing taxanes in the adjuvant setting," Giordano said.

In fact, use of Taxol and other taxanes as adjuvant breast-cancer therapy rose from a rate of just over 5 percent of patients before the ASCO presentation, to close to 24 percent soon after the conference.

More alarming, doctors at first limited Taxol treatment to women with lymph node-positive breast cancers, but gradually extended its use to cases without lymph node involvement -- even though there was no data to support the drugs' efficacy against these malignancies.

The story did have a happy ending: Longer-term data, published in 2003 in the Journal of Clinical Oncology, found Taxol to be of real benefit to women battling lymph node-positive breast cancers.

But not all stories end so well, the study authors warned. They listed examples such as hormone replacement therapy (HRT), now-banned cox-2 inhibitors such as Vioxx and Bextra, and Iressa, a lung-cancer drug that physicians turned to based on early findings, only to find out later that it might do more harm than good.

No one is advocating that researchers withhold early results from their peers or the public, however.

"If there are breakthroughs in the field and new treatments that are truly showing a benefit, then we want to know about that as soon as possible, to be able to pass that on and change our practice," Giordano said.

On the other hand, Schwartz said doctors and patients need to "bring a little skepticism" to data reported outside of major, peer-reviewed journals. She pointed out that presentations at meetings are simply not subject to the kind of review that happens before a study is published in a journal. That fact gets lost in the media attention surrounding "promising" new findings, however.

"There's a lot of hyping of results -- some of it comes from industry, where they often present results using relative terms, magnifying the benefit and minimizing the harms," Schwartz said. A drug company's stock can also spike upwards on the basis of preliminary trial results, she added. "So, there are all these other interests that are promoting drugs to be portrayed in a very favorable light."

It's not hard to see how doctors and media-savvy patients can get swept up in all this, the Dartmouth expert said. But Schwartz advised that, before patients jump at a new drug, they step back and ask a few simple questions first.

"Is there really a big difference in something that patients [in the trial] experienced -- how long they lived, what their quality of life was? Is this coming from the 'gold standard' -- a big, randomized trial with a control group? What about side effects?" she said.

Schwartz also offered up one more piece of advice: To remember that when it comes to drugs, "new" is not synonymous with "improved."

"There's the assumption that the newest drug is the latest and greatest," she said, "but that's not always the case. And if there are already existing [treatment] options that have better science behind them, it's often better for people to take those proven options instead."

More information

For more on clinical trials, visit the U.S. National Institutes of Health.

SOURCES: Sharon Giordano, M.D., M.P.H., assistant professor, medicine, department of breast oncology, University of Texas M.D. Anderson Cancer Center, Houston; Lisa Schwartz, M.D., co-director, V.A. Outcomes Group, Department of Veterans' Affairs, White River Junction, Vt., and associate professor, medicine, Dartmouth College, Hanover, N.H.; March 15, 2006, Journal of the National Cancer Institute, March 15, 2006, Journal of the American Medical Association
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