"The reasons we had to suspend the treatments had less to with the perception of danger . . . than with other purely practical considerations," Breitner said. "It's all very unfortunate."
Other Alzheimer's researchers expressed similar disappointment, saying they feared the developments would unnecessarily derail a promising line of research.
"We should not give up on this," said Linda Van Eldik of the Northwestern University Feinberg School of Medicine in Chicago. "Inflammation is a key player in the damage in Alzheimer's. I would hate to have something like these initial results make people stop this whole area of research, because I think it's really important."
Similarly, researchers leading the two large breast cancer trials decided to discontinue parts involving Celebrex in part because of the health concerns, but primarily because they felt the rising alarm made it impractical to continue.
"We were concerned that, because of the widespread media attention around this class of agents, the reaction of ethics review committees around the country, and the volume of telephone contacts we were having from study participants, that the entire machinery of our clinical research program would unravel if we tried to persist," said Paul Goss of the Massachusetts General Hospital in Boston, who is leading the studies.
The researchers are proceeding with the primary part of both studies, which will test another type of drug known as an aromatase inhibitor in thousands of patients in the United States, Canada and Spain.
"We felt we were being caught up in the eye of the storm, and it would be even more harmful to us if this decision had to be made further down the road," Goss said. "I'm very disappointed. In my heart, I don't believe that blanket withdrawal of this scientific endeavor is the most productive decision to be made."
Goss and others said that even if it turns out Celebrex and similar drugs do increase the risk of heart attacks and strokes, many patients may be willing to take that risk to cut their chances of getting cancer, especially if it runs in their families.
"For women with a very high risk of breast cancer, if there is an opportunity for them to benefit, it may strongly outweigh a cardiovascular risk," Goss said.
Other researchers agreed, saying what might emerge is a more targeted use of these drugs only for those at low risk for heart disease and high risk for other diseases.
"I hope what's going to emerge from this is that we're going to understand risk and benefits more clearly and quantify them more explicitly," said Bernard Levin of the M.D. Anderson Cancer Center.
Elias A. Zerhouni, director of the NIH, defended the agency's actions, saying even a hint of risk warranted discontinuing the Alzheimer's trial because it involved healthy people. "You have to err on the side of doing no harm," he said.
But Zerhouni agreed that once the risk is better understood, it could turn out that the drugs or others like them could still be useful, either for selected patients or by taking countermeasures.
"We shouldn't shy away from this class of drugs because of Vioxx. If you can demonstrate a benefit that is non-zero, then you have to evaluate risk versus benefit," Zerhouni said. "The inflammation theory is a very valid and strong mechanistic approach."
Several researchers noted that evidence has continued to mount that cholesterol-lowering statin drugs cut the risk for heart attacks in part through their anti-inflammatory effects. Some evidence has suggested they, too, may reduce the risk for cancer.
Part of the problem for drugs such as Vioxx and Celebrex is that companies are focused on developing drugs that can be marketed to large numbers of patients, said Carl F. Nathan of the Weill Medical College of Cornell University in Ithaca, N.Y.
"We have to stop demanding that every drug be a blockbuster," Nathan said. "What we have to go back to is smaller markets for individual drugs. We have to take good drugs and market them conservatively and increase our knowledge of the settings where the risk-benefit ratio is best."
Other researchers said they were pessimistic that drugs such as Celebrex would ever reemerge as major players for disease prevention, but the underlying concept remains highly promising. As a result, the focus is likely to shift to developing drugs without the negative side effects.
"I'm really cautious now. Anything we come up with, we'll have to evaluate carefully after this," DuBois said. "There are other ways to attack this pathway, and there are other agents in early development. I think now they could be moved up now. We'll have to see what new drugs might pop out from people looking at this in a different way."
