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Crisis Looms in Cancer Research Traditional Methods of Assessing Success May Be Obsolete

Posted on: Thursday, 22 December 2005, 18:00 CST

By Gardiner Harris

Despite promising discoveries and multibillion-dollar investments, cancer research is quietly undergoing a crisis. Federal drug regulators will soon announce several initiatives that they hope will help salvage the field. Few drugs are being marketed, and most of those that have been introduced are enormously expensive and provide few of the benefits that patients expect. Officials of the Food and Drug Administration suggest that the failures may result from an obsolete testing system.

There is growing evidence that X-rays, the longtime standard, may not accurately assess a patient's disease. So the FDA is creating collaborations to uncover new imaging, blood and other tests that may better signal the progression of cancer.

"We need to develop cancer drugs differently," the chief operating officer of the agency, Dr. Janet Woodcock, said in a recent interview. "The tools we have to develop these treatments are not what we need in cancer."

On Tuesday the agency approved Nexavar, a drug described as "a major advance" in treating kidney cancer. Its approval demonstrates the global confusion surrounding cancer. The manufacturer of Nexavar, Bayer, used X-rays to determine that the drug doubled the time, to 167 days from 84, before tumors grew substantially in number or size. FDA officials found the findings so compelling that they urged Bayer to stop the trial early and give Nexavar to subjects who had been taking placebos.

European regulators, on the other hand, wanted the trial to continue because they wanted Bayer to prove that Nexavar actually extended lives, a finding that would have taken many more months to establish, a deputy commissioner of the drug agency, Dr. Scott Gottlieb, said Tuesday in an interview.

"Nexavar is a good example of how we have developed better science around the development process itself that not only enables these drugs to come to market but to come to market more quickly," Gottlieb said. Still, much work remains to be done, he said, adding: "The crux of the crisis in oncology is that for years we have developed tremendous scientific advances in looking at how cancer develops, and that's not being translated into practical solutions that are benefiting patients at the pace you would expect. Look at what the government and all the drug companies are spending, and yet drugs are not reaching the market. They're being hung up in the development process." Groups of cancer patients say they, too, want better ways to measure success against cancer. "That doesn't mean we want drugs pushed through faster," the president of the National Breast Cancer Coalition, Frances Visco, said. "It means we want better science, meaningful endpoints and drugs that have less toxicity and actually prolong survival." Researchers are not alone in their failures. Drug makers are in the midst of an alarming dry spell that threatens the very foundations of the industry. After peaking in 1996 at 53, the number of new drug approvals has steadily declined. This year, it is unlikely to exceed 17.

Only one in 20 prospective cancer cures used in human tests reaches the market, the worst record of any category of medicine. Among those that gained approval in the last 20 years, fewer than one in five have been shown to extend lives. And those life extensions are generally measured in weeks or months, not years.

FDA officials are increasingly concerned that failures with cancer may result because the science of human testing, called drug development, has not advanced as rapidly as the understanding of the biology of cancer.

"My concern is that these novel drugs being discovered will bump up against an aging development process that can't adapt as quickly," Gottlieb said.

The agency will soon release a report that lists more than 12 research areas that it will address to try to improve clinical trials.

Among the efforts is a search for new ways to measure cancer progression. For decades, X-rays have been the principal means for researchers to judge whether a cancer drug works. If tumors appear to shrink or stop growing after therapy, the drug is thought to be working.

But there is growing evidence that tumor size may not matter much. Small tumors can be as deadly as large tumors. That discovery has unmoored drug development. If X-rays are poor predictors of cancer progression, how can researchers tell whether a drug is working?

Researchers could track which patients live or die. But trials that measure life expectancy often take years and tens of millions of dollars to complete. The FDA is setting up collaborations with other federal agencies to pursue alternative technologies, blood tests and genetic screens. Officials are particularly hopeful about research into positron emission tomography, or PET scans. The scans show not only a tumor's size, but also its vigor.

Source: International Herald Tribune

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