Cancer Decisions - Free Newsletter

HERE AT THE MOSS REPORTS

The one thing we all seem to have too little of these days is time. This is as true for the medical profession as it is for everyone else. While your doctor would almost certainly like to spend more time with you, to explain things in more depth and answer your questions more fully, the constraints imposed by the today's managed care system conspire to make the allocated time per visit ever shorter.

Robbed of the opportunity to discuss their medical needs thoroughly with their physicians, people often turn to the Internet for answers. Certainly, the Internet has unlocked the medical libraries and made vast quantities of formerly unavailable medical literature accessible to everyone. But it has also made available an abundance of unreliable information, often couched in pseudo-scientific language, whose concealed purpose is to sell the unwary a product or service that is essentially worthless. Without the necessary background in the life sciences, it can be extremely hard to discern the fallacies in the sales talk or make sense of journal articles and technical literature.

For thirty years I have been studying cancer and its treatment, monitoring emerging research and writing about new approaches to cancer in the fields of both conventional and alternative medicine. The Moss Reports are the distillation of my long involvement with the field of cancer. Each report presents the available treatment options for that particular kind of cancer, discussing the rationale behind the treatment and objectively analyzing the expected success rate, drawbacks and alternatives.

When the diagnosis is cancer, medical decisions must be made quickly, and in the current climate of rushed doctor visits it is not always easy to obtain the focused, relevant information you need in order to make good choices.

If you would like to order a Moss Report for yourself or someone you love, you can do so from our website, www.cancerdecisions.com, or by calling 1-800-980-1234 (814-238-3367 from outside the US).

Also downloadable from our Web site are the Current Topics reports on important issues in the field of cancer prevention and treatment. These reports are priced at $9.95 each. Currently available are the following:

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)
Do Antioxidants and Chemotherapy Conflict?
Mammography, Biopsy and the Diagnosis of Breast Cancer
The Politics of Hope: Andrew von Eschenbach and the Decline of the National Cancer Institute
The Mexican Cancer Clinics in the Era of Evidence-Based Medicine

For those who have already purchased a Moss Report, a phone consultation can be enormously helpful in narrowing down the options and arriving at a coherent treatment strategy. A recent phone consultation client wrote:

"The telephone consult with Dr Moss was extremely valuable, informative, and provided several optional courses of action for me to take at this stage of my disease process. Dr Moss was open, helpful, friendly, and backed up his comments with scientific evidence that seemed to be at his fingertips. The support people that were present all took part in the phone consult and Dr Moss had no difficulty sharing and explaining things to them. I am now able to directly reach him through his personal email if I want any more information. A very satisfying experience, and well worth the expense." — JF

If you are a Moss Report client and would like to schedule a phone consultation, please call 1-800-980-1234 (814-238-3367 from outside the US) or send an email to: Jacquie@cancerdecisions.com.

We look forward to helping you.

WAR ON CANCER - A MORE NUANCED PERSPECTIVE

The big cancer news this week was an announcement by the American Cancer Society (ACS) that for the second year in a row the number of US cancer deaths has fallen. It brought a storm of media activity, most of it along the lines of "US Turns Corner in the War on Cancer." But, as with last year's similar announcement, the cancer establishment is exaggerating the improvement and also trying to use it to score points with Congress and the public.

Few reporters could withstand this sort of concerted propaganda barrage. One who consistently does so is the respected journalist Gabe Pressman, senior correspondent at WNBC-TV. Gabe has been a reporter for almost 50 years and is called the "reporter's reporter," for his honesty, intelligence and integrity. This time, he sought out a more nuanced perspective for his WNBC health blog. See his interview with me and with Prof. Samuel Epstein on the subject of the ACS announcement. Pressman's commentary "Are We Winning The War On Cancer?" can be found at the WNBC Web site:
http://www.wnbc.com/health/10786820/detail.html

I hope to explore the question of these changes in cancer mortality figures more fully in a forthcoming newsletter.

A CANCER DRUG BITES THE DUST

Technically, Telcyta is what is known as a "pro-drug" – i.e., a drug that is administered in the form of an inactive precursor that only becomes pharmacologically active once it has been absorbed and partially metabolized by the body.

When it was introduced, Telcyta was considered an exciting departure among cancer drugs, a targeted agent that worked via a unique and novel mechanism. Many cancer cells overexpress (over-produce) a form of the enzyme glutathione-S-transferase P1-1 (abbreviated GST P1-1), whose normal biological function is to detoxify a wide range of compounds. When overexpressed, GST P1-1 confers drug resistance on the tumor, allowing it to survive – and sometimes even to thrive – through various anti-cancer treatments, such as chemotherapy. GST P1-1 splits Telcyta into two separate compounds, one of which is actively cytotoxic (cell-killing), while the other binds to the enzyme irreversibly, reducing its ability to inactivate further chemotherapy.

There is no doubt that the design of this drug is based on an ingenious and elegant theory – but how well does it work in clinical practice?

In October 2003, the drug's manufacturer, Telik, Inc. of Palo Alto, CA, announced what it called "positive interim results" from its phase I-II clinical trial of Telcyta in combination with the chemotherapeutic drug carboplatin in the treatment of ovarian cancer. In a press release that was reported at the National Cancer Institute's Web site, Telik claimed that an astonishing 88 percent of patients achieved stabilization of their disease on this regimen. But a closer reading of the press release showed that this impressive-sounding result was based on an evaluation of only 8 patients! Five of these 8 had exhibited "objective tumor responses," which is the term often used to describe a temporary (for a period of one month or more) partial shrinkage of the tumors. One of the 8 patients did have a complete response (i.e., total tumor disappearance), but complete responses are also almost always a temporary phenomenon. (How long the response lasted in the case cited in this trial was not revealed.)

Wall Street Interest

Every drug has a commercial, as well as scientific, 'personality.' As far back as 2004, financial analysts who cover the medical field had been closely watching Telcyta, and promoting it as "the most promising unpartnered, small-molecule compound in late-stage development." Following the aforementioned press release detailing the interim results of the phase I-II trials, enthusiasm for Telcyta reached a peak, with various news articles referring to it as an "active drug," "a promising breakthrough" that was "effective in various cancers," including not just ovarian but non-small cell lung (NSCLC) and kidney cancer as well. Excitement over Telcyta mounted and shares of Telik soared past $22 on the NASDQ market, leading analysts to push the company's stock even more vigorously.

Because of its perceived value, Telcyta was rapidly moved into several large phase III trials, under the general umbrella of a group of clinical trials known as ASSIST, which stands for "Assessment of Survival in Solid Tumors." ASSIST-1 was a single agent trial (i.e., Telcyta given on its own, without concurrent chemotherapy) in advanced, treatment-resistant ovarian cancer; ASSIST-2 was a single agent trial in treatment-resistant non-small cell lung cancer; while ASSIST-3 was a trial to evaluate Telcyta in combination with the chemotherapy drug carboplatin in advanced ovarian cancer.

On December 26, 2006, Telik announced the results of these three ASSIST trials, but the news was not good. In the ASSIST-1 and ASSIST-2 trials, there was no statistically significant improvement in overall survival. In ASSIST-3, there was some dispute over the results. A total of 244 patients were randomized in an attempt to demonstrate a statistically significant improvement in overall tumor response to the combination of Telcyta plus carboplatin compared to an older drug called liposomal doxorubicin, in patients with advanced, treatment-resistant ovarian cancer.

Under the trial protocol, patients were supposed to receive treatment until either their tumors progressed or there was unacceptable toxicity. However, Telik claimed there was "a major discordance" between the clinical review of the tumor scans done by doctors conducting the trial and the results of an evaluation carried out by an independent radiology review board. On the basis of the judgment of the independent review board, about 25 percent of the patients were discontinued "prematurely" (the company's word) from the assigned study treatment.

Telik claimed that this decision had in effect hamstrung the trial, and that the study was therefore "compromised and no longer suitable for a regulatory submission." However, it is hard to give much credence to such claims. Why would an outside board deliberately sabotage such a trial? As a general rule, the opinion of an independent review board would seem to carry greater weight than that of investigators who are more likely to have a vested interest in the outcome of the trial.

"These results are extremely disappointing," admitted Michael Wick, chairman and CEO of Telik. "We are conducting additional, detailed analyses of the data from these three trials and plan to discuss those results with our advisors to determine the next development steps."

There does remain one more trial, ASSIST-5, which is still open for enrollment. This is a randomized study of Telcyta plus the chemotherapy agent liposomal doxorubicin versus chemotherapy alone as a second-line approach in advanced, treatment-resistant ovarian cancer.

Telcyta was by far Telik's lead product. Not surprisingly, therefore, the company's stock plunged in value after the post-Christmas announcement of the failed clinical trial. In fact, it lost 75 percent of its billion-dollar capitalization in just one day, and rapidly approached an all time low ($4.43 per share). Wall Street quickly soured on the stock. "We see no residual value in Telik's technology beyond Telcyta," said Edward Nash, an analyst at Stifel Nicolaus in New York. He lowered Telik's shares to "sell" from a previous "buy" recommendation. Nash also said in a note to investors that he did not expect the drug to show favorable results if more trials are done. (The stock is currently trading at just over $6.)

What lessons can be drawn from the sudden collapse of Telcyta?

Once again we are made aware of the need to regard preliminary results, especially those ballyhooed in the media, with a considerable degree of skepticism. A few partial responses – even including isolated complete responses - in a handful of patients are not a sufficient basis for drawing any conclusions about the effectiveness of a new treatment. There is simply no substitute for large, properly conducted clinical trials, with independent evaluators and a focus on overall survival. Telcyta failed when its promoters were required to prove that it actually extended overall survival in a challenging patient population.

Unfortunately, many drugs have been approved over the past decade based only on promising, but preliminary, data. It is far easier to reach the benchmarks of temporary tumor shrinkage (partial responses) or a fluctuation in biochemical markers. For example, to name but a few, the following drugs were all given "fast track" accelerated approval by the Food and Drug Administration (FDA): Xeloda (1998), Campath (2001), Arimidex (2002), Velcade (2003), Iressa (2003), Erbitux (2004). Once drugs such as these are approved they rarely are reevaluated for their safety and actual clinical effects in general practice.

In a sense, one might even feel a bit sorry for Telik, Inc. So many other drug manufacturers have been granted rapid FDA approval for their drugs without providing rigorous proof of actual survival benefit to patients. But think how much less rosy the public's overall perception of progress in the war on cancer would be if every manufacturer were required to prove that the drugs they produce actually extended survival in such rigorous, independently-reviewed phase III randomized trials.

--Ralph W. Moss, Ph.D.

References:

Preciphs, Joi and Larkin, Catherine. Telik's Shares Plunge as Cancer Drug Fails in Trials (Update7), Bloomberg News, Dec. 26, 2006. Available at:
http://www.bloomberg.com/apps/news?pid=20601087&sid=aNla7DSdW9r4&refer=home

Reported at NCI Web site:
http://ctep.cancer.gov/resources/gcig/news102103a.html

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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.