Lorne Cancer report: call for new trial parameters

A prominent cancer researcher has told the Lorne Cancer Conference that many experimental cancer drugs are being discarded as having no value in prolonging survival in cancer patients, but the problem may lie with the clinical trial process.

"There has been a dramatic decline in new drugs being registered," says Prof Rick Kefford, a clinician and researcher at the Westmead Institute for Cancer Research. "We might be throwing the baby out with the bathwater."

According to Kefford, there are problems with the way drugs are tested in clinical trials, in particular with the primary endpoints used to evaluate the performance of new drugs.

"Drug registration is traditionally based on survival times and tumour shrinkage -- they are bias-free and robust endpoints, but probably too stringent," he told the conference. "We need other endpoints."

The problem, Kefford said, is that for ethical reasons, most drugs are tested in patients with advanced cancers. But these patients may not exhibit extended survival times in response to the drug, which may be far more effective at stabilising tumours or sending a patient into remission when used to treat earlier-stage disease.

He said he advocated the use of new endpoints, such as the use of PET scans to identify and measure the metabolic effects of a drug on a tumour, before physical changes can be observed. The use of tumour-specific molecular markers can also be used to follow the effects of new treatment regimes.

But the US Food and Drug Administration is reluctant to change its standards in the evaluation of new chemotherapeutics. Kefford said that in trials in which he had been involved, the use of PET data had met with resistance from regulators.

There is also a need to conduct multi-pronged synergistic trials of new drugs with existing drugs, or combinations of new drugs, Kefford said. But again, he said, regulators are reluctant to accede to such trials, particularly when it comes to combining new drugs.

Look for a comprehensive wrap-up of the Lorne Protein, Cancer and Genome conferences in the march issue of Australian Life Scientist