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A CLIENT'S COMMENT

This week my staff and I received a wonderful letter from a Moss Reports client, which he has agreed to let us share with you. It reads in part: "I want you to know how much it means to me to be able to confer with the 'Moss Network' on these life and death decisions. I also want to thank you and Dr. Moss for your speedy responses to my time critical questions…Thanks again for your help in our time of need!!" -Dennis H.

We are always happy to be of help. Our office is open during normal East Coast business hours, but our telephone service is always ready to receive calls at 800-980-1234. If you explain your needs, one of our staff members will call you back as soon as humanly possible. We offer written reports on a large number of cancer types. I am also now available to my clients for phone consultations. But whether you become a client or not, you will always be treated with courtesy and respect by Anne, Diane, Louise or myself. For the last twelve years, we have been dedicated to informing cancer patients about their best choices through the Moss Reports. So let us know if we can be of help to you, a friend or loved one. Speaking of which, many of our clients have sponsored a Moss Report for someone with cancer as a way of showing how much they care.

A QUESTIONABLE DRUG IS APPROVED

The FDA has approved the drug Iressa (gefitinib) for the treatment of non-small cell lung cancer, despite evidence that it does not prolong the lives of patients. Approval came after an FDA panel heard testimony from patients, one of whom claimed to feel much better after taking the little brown pill. Her moving story helped convince members of the Oncologic Drug Advisory Committee to give final approval.

The Committee, which has the responsibility for making some of the most momentous decisions in medicine, is composed almost entirely of conventional oncologists. Even the incoming "consumer representative" on the panel is the head of hematology at Washington, DC's Lombardi Cancer Center. While it is of course entirely appropriate that the opinions of the medical profession should be pivotal in the decision-making process, there is also little doubt that such reviewers are predisposed to take a very favorable view of new cancer drugs and are unrepresentative of the wide spectrum of people who will be affected by the Committee's decisions.

Some critics are beginning to wake up to the fact that the FDA is now approving drugs that emerge from "Big Pharma" without requiring the rigorous proof once considered necessary. In fact, when proof is offered that the drugs in question do NOT work it seems that the FDA is quite willing to throw out the studies and revert to anecdotal accounts.

Something alarming is happening in the Bush administration's approach to drug approval. But, to be even-handed, this problem did not begin with the current administration. It dates back at least to the Clinton era, when the FDA began to approve drugs based on small phase II studies, without benefit of larger and more rigorous randomized phase III clinical trials. Now, under Bush, a new trend emerges: drugs that have actually FAILED phase III trials are being approved anyway! In this Orwellian world, scientific failure means economic success for the powerful drug industry.

We are told that such lax enforcement and bending of the rules are necessary because of pressure from patient groups. But who exactly leads these groups? Just as oncologists can become "consumer representatives," so "patient groups" may represent the interests of Big Pharma as much as (or more than) patients.

Way back in my Memorial Sloan-Kettering days I was offered cash bribes by drug company representatives who wanted access to scientists. (To their amazement, I turned them down.) Today, modern companies have many ways of influencing patient advocates other than by the use of under-the-table envelopes. The Pharmaceutical Research and Manufacturers Association (PhRMA) has itself published a newsletter, The Patient Advocate, featuring stories about FDA reform initiatives that are naturally friendly to the industry. The Biotechnology Industry Organization (BIO), the trade association for biotechnology companies, has sponsored a grassroots organizing conference, while the Health Industry Manufacturers Association (HIMA), which represents manufacturers of medical devices, has lobbied patient advocacy groups.

"We've been dined and romanced and invited," says Abbey Meyers, president of the National Organization for Rare Disorders (NORD). "The companies…give you a complete propaganda presentation."

The National Association of Breast Cancer Organizations (NABCO) is one of the most successful patient advocacy organizations in the US. Its highly regarded chairperson serves on the Board of Scientific Advisors of the National Cancer Institute (NCI), the only layperson in that prestigious position. How is such an organization funded? Here are some of the companies currently listed at NABCO's website as major contributors: Amgen Inc.; AstraZeneca Pharmaceuticals; Aventis Pharmaceuticals; Avon Products, Inc.; Bayer Diagnostics and Oncogene Science; Bristol-Myers Squibb Oncology; Bristol-Myers Squibb Consumer Division; Eli Lilly and Company; Ethicon Endo-Surgery, Inc.; Fischer Imaging Corporation; Genentech, Inc.; GlaxoSmithKline; Longs Drug Stores; Myriad Genetic Laboratories; Novartis; Ortho Biotech, Inc. Pfizer, Inc.; Pharmacia Corporation; Roche Laboratories, Inc.; and Trex Medical Corporation. The situation is the same at many of the so-called patient advocacy groups in the cancer field. Financial success means accepting the largessse of Big Pharma, with all that that implies.

'Rolling Reviews'

Speedy approval is part of what the FDA calls a "rolling review." The idea is to give people who have life-threatening diseases, such as cancer, quick access to new drugs. Not a bad idea, at least in principle. But what is often forgotten is that the risks involved in approving ineffective drugs are enormous. The public has every right to demand a rigorous drug approval process that requires manufacturers to demonstrate both the safety and effectiveness of their products. Yet now, with Iressa, we have approval of a drug that has been shown NOT to work! Once it is on the market, Iressa can readily be prescribed to treat all desperate patients, including those who have kinds of cancer for which there is even less rational basis for its use than there is in non-small cell lung cancer.

Iressa's manufacturer, AstraZeneca, is good at shaping public opinion about its drug. The company "has already been reprimanded by the FDA for giving out misleading promotional materials about Iressa at a meeting for cancer specialists in 2001," says the magazine New Scientist, which recently ran an expose on the controversy. AstraZeneca claimed that there was enhanced anti-tumor activity and a "significant increase in survival" when Iressa was given in combination with chemotherapy. But clinical trials demonstrated that this was not the case. "How many doctors left that meeting determined to prescribe Iressa in this way as soon as it became available?" asked the New Scientist.

When it originally sought FDA approval for Iressa, AstraZeneca submitted data from two relatively small and non-rigorous trials. The patients, who had failed to benefit from other chemotherapy, were given either one or two pills of Iressa. According to the company, tumors shrank in just 10 per cent of these patients. More importantly, the reader should understand that there is no one-to-one correlation between shrinking a tumor and increased overall survival.

With a "rolling review," a drug can supposedly be taken off the market if additional studies do not confirm its effectiveness. But in this case two large randomized Phase III trials in Europe have already shown that Iressa is no more effective than placebo as a first-line treatment in combination with chemotherapy. These results were reported in October, 2002 at the European Society for Medical Oncology congress.

To repeat, it is already known that the drug has not worked in large-scale trials. Yet, in a 'Through The Looking Glass' decision, the FDA approved it anyway! The FDA team leader, Oncologic Drug Products Division Deputy Director Grant Williams, acknowledged that Iressa was the first cancer drug submitted for rolling review "when definite data in another related setting show a lack of efficacy."

So, what is the real meaning of "rolling review"? Big Pharma rolls right over the review process? Or FDA rolls over in the face of intense company pressure?

Lung Damage

AstraZeneca touts Iressa as a relatively non-toxic drug that can improve quality of life. But Iressa is not without potentially serious dangers. In some patients, it has been associated with an aggressive form of pneumonia called interstitial lung disease (ILD). Iressa was approved in Japan in July 2002 and about two percent of the lung cancer patients who were taking the drug got ILD, around one in three of them dying.

In February, 2003, the company admitted that the number of deaths linked to Iressa in Japan had risen to at least 173. The dead were among 473 patients who developed lung disorders blamed on the drug, a company official said. This fatality figure did not include patients who died from side-effects other than lung disorders. A previous report in December, 2002 linked 10 out of 124 deaths at that time to those other side-effects. No updated total of Iressa-caused deaths was available, however.

This drug is one of a new generation of drugs that targets particular molecules on the cancer cell's surface, in this case the EGFR receptor. A relatively small number of patients have a significant enough over-expression of these receptors to make treatment benefit likely. What companies like AstraZeneca would like to do is to carefully design future clinical trials so that only people with lots of the target receptors are included in the study. The results might then be very impressive, with response numbers good enough to gain speedy FDA approval. They would also generate a positive "buzz" among patients and patient groups, which are so susceptible to the perception of good news in an otherwise overwhelmingly bleak picture. Once approved, however, such drugs would then be available to all patients, even though the vast majority would not benefit from them - and a substantial number will likely sustain serious harm.

We can see this happening with Iressa, even though the results so far have been a failure. Already, one reads of doctors using Iressa, alone or in combination, for breast, ovarian, colorectal, prostate, and head and neck cancer. There is no more evidence to support this choice of drug than there is in the case of non-small cell lung cancer, where clinical results have been very far from promising.

Articles in the scientific journals are already asking "why Iressa failed". Yet, despite that, the FDA has unleashed this patently ineffective drug on the world. The approval is a gift to AstraZeneca, Europe's second largest drug manufacturer. Last August, when word got out that Iressa had flunked its phase III trials, the company stock plunged $6.02, to $30.98, a loss of over 16 percent. In fact, the company lost $7.2 billion of its total market valuation on that one day! Today it's back to trading at $41 per share, thanks to a compliant FDA and its highly flexible and convenient policy on what constitutes "proof" of a drug's effectiveness.

Are we now to understand that drugs can be approved based on a few Phase II studies and some emotionally harrowing testimony by patients? The question is important because many complementary and alternative medical (CAM) treatments might qualify for approval under these new and laxer rules. Are we to assume that many such treatments can now gain approval, as Iressa did, with minimal data, even in the face of negative Phase III trials?

We are often told that "equal justice under the law" is the hallmark of our civilization. So it is fair to ask whether this new FDA attitude will apply to everybody, or only to big and well-heeled pharmaceutical companies?

DRUG COMPANIES STEP UP LOBBYING EFFORTS

In a related development, the drug industry has stepped up its lobbying of Congress, US states, and even foreign governments in order to further its economic interests. The industry is worried that price controls over the rising cost of drugs will cut into its profits. The Pharmaceutical Research and Manufacturers of America (PhRMA) will spend $150 million on these efforts in the coming year, a 23 percent increase over last year. The industry has put together an "intellectual echo chamber" of "thought leaders" to speak out on their behalf, says an internal document published by the New York Times (6/1/03).

This year alone, PhRMA will spend $12.3 million to develop coalitions and alliances with doctors, patients, universities and minority groups. The industry has earmarked between $2 and $2.5 million to pay research and policy organizations "to build intellectual capital and generate a higher volume of messages from credible sources" that are sympathetic to the industry. It has also allocated $555,000 "for placement of op-eds and articles by third parties" and $680,000 for "media relations consultants."

Sen. Richard J. Durbin (D-IL) has said that PhRMA "has a death grip on Congress." And Sen. Charles E. Schumer (D-NY) has said that the drug industry is becoming "despised and hated" because of its aggressive efforts to keep prices and profits high.

DEPARTMENT OF CORRECTIONS

Last week I referred to my award presentation speech to the American College for the Advancement of Medicine but in the last paragraph mistakenly referred to this outstanding medical society as "ASCO" (which in fact stands for the American Society of Clinical Oncology). Well, someday perhaps I'll get an award from ASCO. But the abbreviation I intended in that newsletter was of course ACAM.

--Ralph W. Moss, Ph.D.

If you are interested in learning more about the best currently available conventional and alternative treatments for many kinds of cancer please consider buying one of our detailed Moss Reports. We have Moss Reports for 214 different kinds of cancer. Please visit our website at www.cancerdecisions.com or call us at 1-800-980-1234.

References:

New Scientist article: http://www.newscientist.com/news/news.jsp?id=ns99993751

Iressa and breast cancer: http://imaginis.com/breasthealth/news/news2.28.02.asp

Iressa and other kinds of cancer: http://intouchlive.com/journals/oncnews/n0007sup3h.htm

Blagosklonny MV, Darzynkiewicz Z. Why Iressa failed: toward novel use of kinase inhibitors (outlook). Cancer Biol Ther 2003 Mar-Apr;2(2):137-40.

Drug companies and patient groups: http://www.opensecrets.org/alerts/v2/ALRTV2N04.asp

Iressa-linked deaths: http://www.asco.org/ac/1,1003,_12-002123-00_18-0025534-00_19-0025535-00_20-001-00_28-002,00.asp

European Iressa results: http://www.esmo.org/

Failure of Iressa with platinum-based chemotherapy: http://www.asco.org/ac/1,1003,_12-002123-00_18-0019458-00_19-0019459-00_20-001,00.asp

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IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.