Cancer Decisions - Free Newsletter

HERE AT THE MOSS REPORTS

This week I begin a two-part discussion of the decision by the FDA to approve the drug Gemzar for use in patients with ovarian cancer.

Most people assume that in order for drugs to be made available to patients, those drugs must be unequivocally proven to be effective through rigorous clinical trials. Yet, surprisingly, this is by no means always the case. Increasingly, we are seeing the approval of new drugs on the basis of only the most marginal evidence of effectiveness – and the recent FDA decision to approve Gemzar for ovarian cancer is a prime example of this tendency.

Studying the medical literature critically and examining the scientific basis of conventional and alternative treatments has been the focus of my long career in the field of cancer. I have written and published extensively on the subject of cancer treatment, including compiling a comprehensive series of individual reports on more than 200 different cancer diagnoses – The Moss Reports – each one of which examines both the standard treatment options that are likely to be offered for a particular cancer diagnosis, and the possible alternative and complementary approaches to that disease.

You can order a Moss Report on your particular diagnosis by calling 1-800-980-1234 (814-238-3367 from outside the US), or you can order and download it directly from our Web site, www.cancerdecisions.com.

In addition, the following useful reports in our Current Topics series can be purchased for $9.95 each, and can be downloaded directly from our Web site, www.cancerdecisions.com:

Mammography, Biopsy and the Diagnosis of Breast Cancer
Do Antioxidants and Chemotherapy Conflict?
Herceptin – or Deceptin? (An evaluation of the use of Herceptin in breast cancer)
Avastin – Your Money or Your Life (A clear-eyed look at the 'targeted' drug Avastin)
The Politics of Hope: Andrew von Eschenbach and the Decline of the National Cancer Institute
Mexican Cancer Clinics in the Era of Evidence-Based Medicine

For those clients who have already purchased a Moss Report and are facing difficult treatment decisions I offer a phone consultation service. A phone consultation offers the chance to discuss the suggested treatment plan and examine all the various possible options. Many people find this service invaluable in coming to an informed decision.

A recent phone consultee wrote:

"It was a pleasure to speak with Dr. Moss. He was warm, gentle and knowledgeable, and I learned a lot....I place such confidence in him. It was a wonderful half hour." — S.M.

To schedule an appointment for a phone consultation please call 1-800-980-1234 or send an email to Jacquie@cancerdecisions.com.

We look forward to helping you.

FDA APPROVES GEMZAR FOR OVARIAN CANCER DESPITE ITS LACK OF EFFICACY - PART ONE

The Food and Drug Administration (FDA) has taken the rare step of overruling one of its own advisory panels and has approved the drug Gemzar (known generically as gemcitabine) for the treatment of recurrent ovarian cancer. Earlier this year, the prestigious Oncologic Drugs Advisory Committee (ODAC) strongly recommended against approval of the drug for this indication. But the FDA - under the acting directorship of Andrew C. von Eschenbach, MD - approved Gemzar in combination with carboplatin for women whose disease had relapsed six months or more after their initial therapy.

In the past, FDA decision-makers have generally followed the advice of their advisory panels, although they are not legally bound to do so. In March, a spokesperson for Eli Lilly, the manufacturer of Gemzar, said that the company was "really disappointed" with the panel's decision. So what happened behind the scenes between March's disappointment and July's triumphant announcement of approval? Lilly spokesman Dr. Gregory Clarke stated that the company had provided the regulatory agency with additional information.

"This is a situation where we were able to provide the FDA with additional analysis of the data that may have given a little more insight on the benefits," he said. Meanwhile, FDA officials have refused to comment on the controversial decision. It seems decidedly odd that this "additional analysis" was provided directly to FDA leaders and not to the expert panel or the general public.

This is also the first time that the FDA has approved an ovarian cancer drug based upon progression-free survival (PFS), rather than on the basis of an improvement in overall survival (OS). The difference between these two measures is not trivial. Although it sounds like a highly desirable outcome, "progression-free survival" merely represents an interval of variable length between the administration of treatment and the point at which the cancer inexorably starts to advance again. Such delayed tumor growth does not necessarily equate to an extension of the patient's lifespan. Indeed, tumors that are arrested temporarily can then advance more rapidly once they begin growing again, and patients may actually live no longer than they would if they had not received the treatment.

The FDA panel found that the combination of Gemzar and carboplatin increased median progression-free survival in patients by just 2.8 months when compared with carboplatin alone. However, the key fact was that there was no difference in the overall length of patients' survival. The Gemzar-added group also experienced more adverse effects.

For those reasons, in March, this panel voted 9-2 against recommending approval of the drug for ovarian cancer. The panel also commented on the weakness of Lilly's trial data and criticized the way the company conducted the 356-person clinical study (Pierson 2006). It was a landmark finding and seemed to indicate a new determination on the part of advisors to draw the line - to tell both the drug industry and regulators that they would have to provide patients with real survival benefits if they expected to reap the huge financial rewards that generally follow approval.

"The main issue is whether adding 2.8 months to median progression-free survival at a cost of additional toxicity with no apparent effect on survival is a sufficient basis for Gemzar approval for this use," an FDA spokesperson said at the time (Wall Street Journal 2006).

Eli Lilly countered, however, that the purpose of the drug was to prevent the cancer from worsening, not necessarily to help patients live longer. But, logically, if the Gemzar-treated patients die at the same time as those denied this additional drug, how can that constitute an improvement in their condition? Didn't their condition worsen significantly after the drug stopped working, so that they then died at the same time as those who weren't given the drug?

The company's other arguments in favor of Gemzar are convoluted in the extreme. Dr. Clark also asserted, in Gemzar's defense, that the drug allowed patients to go longer without being treated again and therefore could help spare them some side effects of chemotherapy. This is twisted logic, since they would now have to face the side effects of both Gemzar and carboplatin in combination - a regimen that carries a greater array of side effects than either drug administered alone.

When he was asked why Lilly did not mention in its press release the drug's failure to prolong life, Dr. Richard Gaynor, head of cancer research at Lilly, said: "I'm not sure that needed to be the focus." Of course not, as long as you're not the unlucky woman with ovarian cancer. Apparently, for Lilly executives, the focus should be kept not on prolongation of life but on the illusory benefit of "progression-free survival," which will bring concomitant benefits to their bottom line.

Dr. Gaynor also claimed that it is often difficult to determine if, and by how much, a particular cancer drug helps prolong life because seriously ill cancer patients often switch back and forth between different treatments. But isn't that precisely why rigorous clinical trials were invented in the first place, to tease apart and analyze the problems posed by the various treatments that patients are offered?

The randomized clinical trial (RCT), gold standard of drug testing since World War II, is now imperiled as never before in America. A glaring double standard is in effect: clinical trials are deemed desirable when they advance the financial interests of big pharmaceutical companies, but are unceremoniously disposed of when they conflict with the pharmaceutical industry's profit agenda. Regulatory agencies by their very nature are supposed to put a restraint on the profit drive of private companies. That is how the FDA's advisory board (ODAC) was trying to function. However, sometimes those agencies become the tools of the powerful industries they regulate, a phenomenon that George Washington University law professor Jonathan Turley has dubbed "agency capture." This is a situation that should attract the attention of every legislator in the country as well as every person who cares about the integrity of the drug evaluation process.

TO BE CONCLUDED, WITH REFERENCES, NEXT WEEK.

--Ralph W. Moss, Ph.D.

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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.