Fwd: THE MOSS REPORTS Newsletter (06/07/03)

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Sat, 7 Jun 2003 03:30:34 -0400 (EDT)

 

THE MOSS REPORTS Newsletter (06/07/03)

 

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Ralph W. Moss, Ph.D. Weekly CancerDecisions.com

Newsletter #86 06/07/03

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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.

 

 

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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

 

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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_20-001-0\

0_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_20-001,0\

0.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.

 

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