Cancer Decisions - Free Newsletter

HERE AT THE MOSS REPORTS

For cancer patients and their families, the need to make important treatment decisions rapidly, and on the basis of an immense amount of new and often highly technical information, can create a feeling of being totally overwhelmed.

The acclaimed Moss Reports can be an invaluable guide at this difficult time. There are now more than 200 individual Moss Reports, each one dealing with a different type of cancer and detailing in depth the best currently available conventional and alternative approaches to that particular diagnosis. You can order a Moss Report on your specific cancer type and download it directly from our Web site at www.cancerdecisions.com.

For those clients who have purchased a Moss Report and are struggling with 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 immensely helpful in coming to an informed decision. 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.

A question that comes up very frequently in phone consultations with my clients is the issue of whether or not it is safe to take antioxidants while undergoing standard cancer treatments such as chemotherapy or radiation.

While there is mounting evidence to suggest that antioxidants are both safe and effective in counteracting the unpleasant side effects of chemotherapy and radiation, by and large the oncology profession tends to recommend strongly against the use of such supportive measures, citing concerns that antioxidants may interfere with the cancer-killing ability of standard treatments.

I have written a 30 page report on this topic, exposing the flaws in the arguments so often leveled against the use of antioxidants during cancer therapy. The report - Do Antioxidants And Chemotherapy Conflict? - is one of our Current Topics series of in-depth analyses of important issues in the treatment and prevention of cancer. These Current Topics reports are available for download from the Cancer Decisions Web site: www.cancerdecisions.com at a cost of $9.95 each. Other available titles include:

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

We look forward to helping you.

IS FDA ADVISORY COMMITTEE TIGHTENING THE RULES FOR DRUG APPROVAL? — PART II

[Last week we began a two-part article on an FDA committee's refusal to approve the new drug, Abraxane. This week, we conclude with a discussion of similar ODAC actions in the past few months. References follow the article.]

The FDA's Oncologic Drugs Advisory Committee (ODAC) also recently rejected approval of the drug Genasense (oblimersen sodium) for use in combination with two standard drugs, fludarabine and cyclophosphamide, as a treatment for chronic lymphocytic leukemia (CLL). While acknowledging that Genasense somewhat increased the rate of complete responses (CR), as well as so-called nodular partial responses by 10 percent, the high-level committee questioned the clinical significance of such regressions. ODAC members pointed out that Genta, Inc., Genasense's parent company, had sponsored a randomized controlled trial (RCT) that failed to show an improvement in (a) overall survival, (b) time to progression, or (c) duration of the response. (Note: these are three commonly used measurements of actual clinical benefit). Susan O'Brien, an M. D. Anderson Cancer Center, Houston, investigator who worked on the Genasense trial and served as one of the company's presenters, countered that the company was being "penalized" for performing a randomized trial.

If approved, Genasense would have been among the first of the so-called "antisense" drugs to come to market. Scientists have thus considered Genasense to be one of an exciting new generation of "smarter" targeted drugs, attacking cancer more specifically than did the first generation of targeted therapies (such as Avastin). However, the failure of Genasense to achieve much in the way of clinical improvement in several kinds of cancer, as well as ODAC's proper recommendation against approval, is a setback for this much-hyped kind of treatment. Previously, the same company had sought approval of Genasense for treating another kind of cancer, advanced melanoma. In 2004, ODAC similarly voted against recommending approval for that use, in the words of some commentators, "clobbering" the company.

According to a report in the well-informed Cancer Letter, M.D. Anderson's O'Brien felt that Genta could have been better served in its leukemia trial by performing a less rigorous study. "I think we are penalizing the sponsor for the fact that they did a randomized trial," she commented. Furthermore, in a revealing statement, she claimed: "Every drug that has been approved in leukemia so far has been approved based on response rate, mostly from single-arm trials. If this were a single-arm trial that showed a benefit in response, compared to historical data, nobody would be raising this issue of time to progression. It's only because this is a randomized trial where we have these two groups, that this would even come up."

I find this to be an extraordinary argument, and ODAC members may have felt the same way, since the committee voted 7-3 against approval. What Dr. O'Brien seems to be saying is that the FDA and its advisory committees have in the past lowered the standard of proof for new cancer drugs by repeatedly allowing agents to be approved based on inadequate phase II trials, and sometimes accepting clinically dubious endpoints (such as apparent changes in response rates). It appears that she is taking ODAC to task for being inconsistent and unfair when the committee should in fact be praised for reverting to the FDA's earlier, and higher, standard of proof, i.e., increased overall survival as demonstrated in randomized controlled trials.

Luckily, there was a patient advocate present at the committee's public hearing session, who understood the importance of maintaining high standards of proof. "We want to make sure that inferior drugs don't start creeping into the standard of care," said Helen Schiff, of the Center for Medical Consumers. "We want to make sure that newly diagnosed women have the very best shot at preventing a recurrence and not dying of breast cancer. It is important to remember that therapy in the adjuvant setting is curative for some women. We want to increase the number who survive, not decrease them. The stakes are very high. Once a drug becomes a standard of care, it can be used as the comparator arm in a registration trial. This is an advocate's worst fear. If the drug in the comparator arm is inferior, you can end up replacing one inferior drug with another inferior drug."

Avastin Also Takes a Hit

In another sign that FDA may be tightening its requirements for anticancer drugs, the biotechnology firm Genentech announced in mid-September that the government agency had delayed a request for the approval of Genentech's widely used colon cancer drug, Avastin, as a treatment for breast cancer, asking for more data on its safety and efficacy. The company said it was confident that it could gather the necessary data by the middle of 2007. But if FDA once again requires proof of actual life prolongation (as they should) this might be a tall order.

Ironically, the company blamed the delay on its collaborators at the National Cancer Institute. According to a report in the New York Times:

"Genentech applied for approval of Avastin as a treatment for metastatic breast cancer based on a trial organized by academic researchers sponsored by the National Cancer Institute. Such academic trials, Genentech said, do not collect and audit data as rigorously and in as organized a form as trials typically run by companies."

This reverses the assumption, common to most observers, that NCI and other unaffiliated scientists generally attain a high level of objectivity in their work, while reports emanating from drug companies are typically presented in a way that distorts both the safety and efficacy of new drugs.

"We're very confident the data is there," Dr. David Schenkein, vice president for clinical oncology at Genentech, said in an interview. Still, he said, "We certainly were surprised and disappointed" by the FDA request.

According to the company, the NCI-sponsored trial had shown that the addition of Avastin to a standard drug, paclitaxel (Taxol), had doubled the median time that it took for breast cancers to worsen, from six months (with paclitaxel alone) to one year (with added Avastin). However, readers should be aware that a delay in the doubling time of a tumor does not by any means translate into an increase in overall survival. And unless the company can show through reliable studies that Avastin-added patients actually lived longer, FDA may decide to continue to withhold approval for this indication.

Wall Street reacted with disappointment to the news and Genentech lost some 5 percent of its valuation. Geoffrey C. Porges of Sanford C. Bernstein & Company wrote that if by some chance Avastin were not approved for breast cancer in 2007, "the revenue loss would be substantial." He is forecasting that use for breast cancer will account for $1.4 billion of Avastin's $5.6 billion in sales by the year 2010.

The generally poor performance of Abraxane, Avastin and Genasense in the latest clinical trials is a cautionary tale about the limitations of both chemotherapy and the supposedly more effective ‘targeted' therapies. While these drugs may eventually find a broader niche in cancer treatment, they have not yet even begun to live up to the wildly exaggerated claims that were being made for them in the mainstream media just a few short years ago.

--Ralph W. Moss, Ph.D.

References:

Associated Press, FDA panel says leukemia drug shouldn't be approved. USA Today, Sept. 6, 2006. Available at:
http://www.usatoday.com/news/health/2006-09-06-genasense_x.htm

Berenson, Alex. Hope, at $4,200 a Dose. New York Times, Oct. 1, 2006. Available at:
http://www.nytimes.com/2006/10/01/business/yourmoney/01drug.html?ref=yourmoney

Branca, Malorye A. Genasense Faces Identity Crisis. Bio-ITworld.com, February 18, 2004. Available at:
http://www.bio-itworld.com/archive/021804/genasense/

Goldberg, Paul. ODAC Nixes Abraxane In Adjuvant Breast Cancer, Genasense Falls Victim To Its Randomized Trial. Cancer Letter, vol. 32, no. 31, Sept. 8, 2006. (Subscription required).

Motley Fool. Avoiding Biotech Land Mines [Commentary] May 13, 2004. Available at:
http://www.fool.com/news/commentary/ 2004/commentary040513ct.htm
(sign-up required)

Pollack, Andrew. Longer Delay for Genentech on New Use of Cancer Drug, New York Times, Sept. 12, 2006. Available at:
http://www.nytimes.com/2006/09/12/business/12gene.html?
ex=1160020800&en=efab615e678f11f6&ei=5070

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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.