WSJ: Pazdur's Cancer Rules - The FDA's oncology chief gets his revenge.

...FDA oncology drugs chief Richard Pazdur is the most important person in the U.S. government when it comes to cancer drugs, and he has never made a secret that he dislikes the accelerated approval process under which Iressa got the green light. Nor has he been shy about suggesting that the agency was railroaded in this drug's case.

The truth is that Iressa-maker AstraZeneca simply refused to play by Dr. Pazdur's rules. In 2002 -- knowing it had plenty of data to qualify for accelerated approval -- the company rebuffed his requests for more trials and appealed directly to something called the Oncologic Drugs Advisory Committee (ODAC)....

Dr. Pazdur tried his best to find reasons to reject the ODAC recommendation, but eventually the FDA relented, granting approval in May 2003....

Dr. Pazdur has also since stacked ODAC with people who share his anti-industry views. Most importantly, the unrelated panic over painkiller safety last fall has created the political cover for Dr. Pazdur to punish AstraZeneca for disobeying his wishes.

Some readers may find it hard to believe that life and death decisions about drug approvals and withdrawals would be made for political reasons. So it's worth pointing out that Dr. Pazdur has admitted doing so before. In 2002, the FDA rejected Erbitux, with Dr. Pazdur admitting it was a "good drug" but that it had a "bad development plan." Erbitux later became a clinical success against colon cancer.

But later that same year when the FDA approved a colon cancer chemotherapy called Eloxatin, Dr. Pazdur approvingly remarked "we want to send a message" about "the value in doing randomized trials." In other words, the less revolutionary drug (Eloxatin) got approved first because its makers had jumped through the right bureaucratic hoops....

Richard Pazdur, MD, is currently Director of Oncology Drug Products, Center for Drug Evaluation and Research (CDER) in the United States Food and Drug Administration (FDA). Prior to joining the FDA, Dr. Pazdur was Professor of Medicine at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. He was a faculty member for 12 years in the Gastrointestinal Oncology and Digestive Disease Department at M. D. Anderson, specializing in the treatment of colorectal cancer. He has served as a Visiting Professor at the Institute of Biomedical Sciences Academia Sinica, in Taiwan, and as a Visiting Consultant for the Manpower Development Act, for the Ministry of Health in Singapore. Listed in The Best Doctors in America in 1994 and in Who’s Who in Science and Engineering in 1996, Dr. Pazdur received his medical degree from Loyola Stritch School of Medicine and completed his internship and residency training at Loyola University, Foster G. McGaw Hospital. He performed fellowship training in medical oncology at Rush-Presbyterian-St. Luke’s Medical Center, and in Oncology/Hematology at the University of Chicago Medical Center. Dr. Pazdur currently serves on the Editorial Boards of ONCOLOGY, Primary Care & Cancer, and Clinical Cancer Research, and is widely published in the medical literature.

keep this in mind...

http://www.ghchealth.com/how-well-tested-are-new-cancer-drugs.html

Contrary to popular belief, drug companies are not required to prove that their drugs prolong survival. Until the mid-1980s, all cancer drugs were approved solely on the basis of what researchers call the “tumor response.” In other words, a drug company needed only show that the drug caused a tumor to shrink, not necessarily to disappear.

Years ago, a change in the approval process was recommended by the FDA’s own Oncologic Drug Advisory Committee. The committee members, primarily cancer experts unaffiliated with any government agency, knew that tumor shrinkage often has little or no relation to survival. The committee proposed the novel idea that a drug company should be required to prove that a drug provided some benefit that was meaningful to the patient, such as increased survival or an improvement in symptoms. The committee argued further that the potential benefit of tumor shrinkage did not necessarily outweigh the substantial toxicity of cancer drugs.

This recommendation was made in the mid-1980s, but change at the FDA comes slowly, as a recent assessment of new drug approvals has demonstrated. From 1990 through 2001, the FDA approved 66 new cancer drugs. Prolonged survival was not proven for 48 drugs. And tumor response was the basis of approval for 35 drugs.

These cautions notwithstanding, the FDA still allows the use of tumor shrinkage as the sole end point in the approval of certain drugs. In 1992, the agency introduced an accelerated approval (AA) process. The idea behind AA is to get drugs quickly to advanced-cancer patients in whom all available options have failed. Consequently, tumor shrinkage was the sole basis of the AA for 10 of 11 new drugs. The rationale: Shrinking a lung tumor might, in the FDA’s view, be “reasonably likely” to alleviate breathing difficulties.

The testing for AA is minimal. The new drug is given to about 30 or so participants who have run out of options. In what is called a phase II trial, there is no comparison group: everyone in the study gets the new drug. Consequently, this type of trial is not likely to provide a true picture of the drug’s toxicity or efficacy. That’s why a drug given AA must continue to be studied to see if it provides any benefit in terms of increased survival or symptom improvement. “The drug companies usually do a large trial in which the new drug is compared to the standard drug,” said Pazdur. “This usually takes two to four years.” And what if the drug company does not comply? “We have a process for rapidly removing the drug from the market,” Pazdur replied.

Still, some not so well tested drugs are available for several years following an AA, and oncologists are free to prescribe them for cancers other than the type for which the products received approval. Or, more often, oncologists can add the new product to a multiple-drug regimen that in itself has never been studied. “Yes, this is called off-label use, which is fairly common in the practice of oncology in the U.S.,” Pazdur agreed. “But this involves the practice of medicine, and the FDA does not control the practice of medicine.” Unless their oncologists tell them, cancer patients do not know whether they are being given a drug off-label. “We would like patients to read the drug label to see the approved indications and contraindications,” advised Pazdur, who said that the information is freely available at the FDA’s web site.

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