(Last week I discussed the approval of ImClone's new "targeted" agent, Erbitux, and showed how the drug had minimal effects against colorectal cancer.)

Analysts speculate that the US market for Erbitux could go to $1.5 billion annually and the worldwide market to $2 billion per year (Coghill 2004). Bristol Myers should therefore quickly recoup what seemed like a ridiculous research investment of $2 billion in a very short time, thanks to the FDA's compliant policy of accelerated approval. Oncologists who sell anticancer drugs in their offices - the so-called "chemotherapy concession" - will also benefit from this largesse (Abelson 2003).

The cost will be borne by individual patients, by Medicare and other insurance companies, private and governmental. And what will society get for this billion-dollar expenditure? If the latest clinical trials are any guide, we will neither see cures nor even significant prolongation of life. Perhaps there may be temporary symptomatic relief for some, if a tumor is blocking the colon or lungs. Hopes will be raised and hopes will be dashed. However, more predictable are the side effects and the peculiar reactions (acne-like rash, difficulty breathing, etc.) that will be experienced by hundreds or thousands of patients, further taxing a medical system that is already at the breaking point.

Patient's Perspective

Many cancer patients and their advocates have waited with growing impatience for this new generation of targeted drugs to come to market. They have often been frustrated with the slow pace of the approval process. In the past I, too, have complained about the reluctance of FDA to approve new treatments. What has now happened, however, is that FDA has done a flip-flop. Not long ago, the agency was agonizingly slow in approving new treatments. They picked over every last detail of a drug application. But now they seem to be rushing to the opposite extreme and to be approving cancer drugs based on inadequate proof of safety or efficacy.

Pressure to approve Erbitux came not just from industry but from some patient advocacy groups. "Sufficient evidence of safety and efficacy existed more than two years ago to justify making Erbitux available to dying patients with no remaining treatment options, the same indication the FDA approved today," said Frank Burroughs, president of the Abigail Alliance for Better Access to Developmental Drugs. "Tens of thousands of colon cancer patients waited and died."

I sympathize with Mr. Burroughs (who lost his own daughter to cancer) in his desire to make new drugs available to patients as quickly as practicable. Any unnecessary delay is deplorable and any unnecessary death is a tragedy. However, there is still no evidence from rigorous clinical trials that the patients about whom Mr. Burroughs spoke so harrowingly would in fact have lived longer had they had earlier access to Erbitux. As an FDA spokesperson took pains to point out, the delay in approval did not mean unnecessary deaths because "all these treatments for advanced cancer don't cure people." Even now, she said, it is not known whether Erbitux prolongs life, only that it shrinks tumors and delays their growth (Pollack 2004). That's a striking admission from an unexpected source.

FDA commissioner Mark B. McClellan, MD, PhD, himself put a positive spin on the drug's approval. "… FDA staff work hard to ensure doctors and patients can have confidence in the safety and effectiveness of new therapies such as Erbitux," he said. "FDA believes it is crucial for cancer patients to have many proven treatment options in their battle against this disease." But notice how the catch phrases "safety and effectiveness" and "proven treatment options" are conflated with the idea of true patient benefit. We are asked, against all evidence, to believe that the partial and temporary shrinkage of tumors is a desideratum in its own right and a reliable predictor of increased survival. This requires an unwarranted leap of faith.

Bitter Irony

Some readers might say, "What's wrong with approving a new drug, even if it only shrinks tumors? The more drugs we have available, the greater the spectrum of choices."

Certainly the range of pharmaceuticals available for the treatment of cancer is expanding rapidly. Yet when looked at from the perspective of complementary and alternative medicine (CAM), there is a bitter irony here. Many non-conventional and non-toxic treatments for cancer have repeatedly failed to get approval as cancer treatments. These include treatments for which there is more documentary evidence of success than can be said for Erbitux. In my first book, The Cancer Industry, I showed how FDA has historically joined other major institutions (the so-called "cancer establishment") in putting insurmountable barriers in the way of promising less-toxic treatments. There are 102 such treatments in my book Cancer Therapy, most of which have been shunned by the FDA. There is simply no economic incentive to investigate these treatments, and this points to a systemic flaw in our entire drug-development system.

Non-conventional treatments are still held to the gold standard of randomized controlled trials (RCTs) that can demonstrate a significant increase in overall survival. Surrogate markers (such as changes in test scores) are deemed insufficient. Case histories, no matter how compelling, are derided by the orthodox medical establishment as "mere anecdotes." Even citing these is said to demonstrate the scientific naïveté of those who espouse CAM.

But with accelerated approval a different - and markedly lower - standard of proof is required of patented drugs emerging from Big Pharma and its partners. For these privileged players, phase III trials showing actual life prolongation have become passé. Multi-billion dollar corporations, which, perhaps not coincidentally, make huge contributions to political campaigns, need only show that their drug shrinks tumors for a month or so. That has become enough to get dubious agents into mass circulation.

Meanwhile, Dr McClellan, the same FDA commissioner under whose jurisdiction Erbitux was approved, announced a few weeks earlier that he intended to crack down on "dangerous" food supplements. Using concern over the herb ephedra (sometimes included in weight-loss formulas) as his springboard, Dr. McClellan pledged to step up FDA's scrutiny of the effects of a broad range of other herbal supplements. "When these regulations are finalized later this year, the public will not be faced with 'buyer beware' any longer," McClellan proclaimed. So it's "buyer beware" for herbs, but "full steam ahead" for highly toxic drugs!

Science By Press Release

We are often told that the difference between 'legitimate' and 'alternative' treatments is that the former are proven through rigorous clinical trials and then scrutinized by the scientific community through publication in peer-reviewed journals, whereas the latter are based on scanty and anecdotal evidence. Yet Erbitux's approval was not based on peer-reviewed studies published in standard journals. Instead, doctors and investigators must rely on FDA summaries and drug company websites. "Science by press release" has now become a standard way of presenting information on new treatments. The obligation to first present one's data to the scientific community through the painstaking process of peer-reviewed publication, followed by carefully documented attempts by independent scientists to replicate any alleged benefits, is now ancient history. What matters is to get the drug to market willy-nilly. Meanwhile, no one in authority seems to find anything wrong with this new commercialized way of presenting medical findings.

Without full-scale and open scrutiny, however, how can cancer researchers as well as the rest of the interested public evaluate claims of efficacy or safety? How can we trust scientific experiments that are carried out by those who have the greatest incentive for coming up with positive results? How can we trust a government agency that shows favoritism to Big Pharma and a corresponding hostility to herbal and complementary medicine?

Simply put, accelerated approval is a process that overwhelmingly benefits Big Pharma. The FDA should return to a standard by which drugs are approved based on the only criterion that really matters: an unequivocal demonstration that such drugs extend life. If drug companies can get accelerated approval for their products, then it should be possible for alternative treatments to be similarly fast-tracked. We must do away with a two-tiered system that is about as democratic as the waiting line at one of Manhattan's exclusive nightclubs.

To order my book, "The Cancer Industry,"
[Click Here].

To order my book, "Questioning Chemotherapy,"
[Click Here].

To purchase my book, "Cancer Therapy,"
[Click Here].

--Ralph W. Moss, Ph.D.

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