Cancer Decisions - Free Newsletter -October 14, 2007

INFLUENCING THE OUTCOME OF CLINICAL RESEARCH

In the past twenty years medical research in this country has increasingly come to rely on the financial support of the pharmaceutical industry - to such an extent, in fact, that industry financial backing is now considerably larger than that provided by the National Institutes of Health.

A group of researchers at the University of North Carolina set out to determine whether, and to what extent, the financial involvement of the pharmaceutical industry influenced the outcome of clinical research. Published in the journal Cancer earlier this year, their report, which focused specifically on the outcome of breast cancer trials, found that clinical studies backed by the drug industry were much more likely to report a favorable result (Peppercorn 2007).

A full 84 percent of industry-backed studies reported positive results, as compared to only 54 percent of those which received no drug company support. And as previous research has repeatedly shown, clinical studies with a positive outcome are far more likely to be published in the medical literature than those with negative findings.

The result of the study comes as no surprise to the many commentators, including myself, who have repeatedly warned that the pharmaceutical industry exerts an unhealthy influence on the way clinical trials are designed, reported and published.

The worth of evidence-based medicine is severely undermined when the evidence on which it is based can be bought in this way. If the medical literature cannot be counted upon for objectivity, how can patients and their caregivers determine which treatments are likely to be of the most benefit? For the newly diagnosed cancer patient, who must quickly make vital decisions based on what is often only a very tenuous understanding of the disease and its treatment, having access to reliable and trustworthy information is of the utmost importance.

HERE AT THE MOSS REPORTS

We are dedicated to helping cancer patients weigh the evidence carefully and critically. For more than 30 years I have studied the subject of cancer and its treatment, and have compiled a comprehensive series of more than 200 individual reports on different cancer diagnoses - The Moss Reports. Each of these reports offers an unbiased analysis of the scientific evidence for current treatment approaches, both conventional and alternative, and offers the cancer patient a clear-eyed, truthful assessment of the available options. A client who recently purchased a Moss Report wrote:

"Having no control over a situation is a very scary thing. When you or someone you love has cancer you find yourself shedding a lot of tears, having a lot of nightmares, and second-guessing every decision you make. I honestly don't know what we would've done without Dr. Moss’s report. I know for a fact it helped us focus on the problem at hand, instead of being consumed by panic and fear. In a place where you feel powerless, it helped us feel empowered. You can’t really put a price on that." - M.M.

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

PHONE CONSULTATIONS

To those who have already purchased a Moss Report I also offer phone consultations. A phone consultation can be enormously helpful in drawing up an effective treatment strategy and getting one's options clearly prioritized. A recent phone consultation client wrote:

"The consultation with Dr. Moss made me see clearer the various options I had, at a time when my mind was just too foggy. He helped me walk out of the maze as though I had a map in my hand." - E.V.

To schedule an appointment, please call 1-800-980-1234 (814-238-3367 from outside the US) or send an email to our Coordinator, Jacquie Johnson, at: Jacquie@cancerdecisions.com.

We look forward to helping you.

CURRENT TOPICS

Also available from our website are our Current Topics reports - a series of in-depth reviews of cancer-related subjects and controversies. Currently available are the following:

On Guard - Gardasil (A discussion of the anti-cervical cancer vaccine Gardasil)
Do Antioxidants and Chemotherapy Conflict?
Mammography, Biopsy and the Diagnosis of Breast Cancer
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
The Mexican Cancer Clinics in the Era of Evidence-Based Medicine

AUDIO NEWSLETTER

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CONFERENCE ANNOUNCEMENT

The Annie Appleseed Project, long a champion of cancer patient advocacy and a consistent source of unbiased information on complementary and alternative cancer treatments, is sponsoring a conference to be held on January 10th-11th 2008, in West Palm Beach, Florida.

The conference - at which I will be among the guest speakers - is titled "Evidence-based Complementary/Alternative Therapies (CAM) for Cancer Advocates." The aim of the conference is to bring together advocates and caregivers from many communities, and to provide a forum for evidence-based discussion of the role of CAM in cancer management.

Full information on conference schedule, registration, etc., please click or go to:
http://www.annieappleseedproject.org/evcamforadc.html

DO STATINS INCREASE CANCER RISK? - PART TWO

(Last week we began a discussion of whether or not the cholesterol-lowering drugs statins are associated with an increased risk of cancer. We presented some research suggesting that statins do not cause cancer, and may even exert a mild protective effect against the occurrence of certain cancers. However, this week we present some important new data concerning possible risks associated with aggressive reduction in low-density lipoprotein (LDL) levels.)

A July 2007 paper in the American Journal of Cardiology has introduced an important new perspective on the issue of statins and cancer (Alsheikh-Ali 2007).

The study, carried out by Dr. Richard Karas and colleagues at Tufts University School of Medicine, Boston, was designed to examine whether there was any relationship between a patient’s blood level of LDL and that patient’s risk of cancer. The study also looked at two other statin-related adverse effects: elevated liver enzymes and a rare - but potentially serious - muscular side effect known as rhabdomyolysis.

Perhaps not surprisingly, the Tufts researchers found that the dosage of statins had a direct influence on the likelihood and severity of adverse effects, with higher dosages being associated with an increased incidence of such effects.

However, Karas and his team also discovered that the lower the blood level of LDL achieved through the use of statins, the greater the risk of cancer. The researchers observed "a significant and linear relationship" between LDL levels and the risk of developing a new cancer, an effect that was especially marked at LDL levels below 100 milligrams per deciliter (mg/dL).

The study concludes: "...the risk of cancer is significantly associated with lower achieved LDL levels. These findings suggest that ...the cardiovascular benefits of low achieved levels of LDL-C may in part be offset by an increased risk of cancer."

These are frightening words, and about the last thing that cardiologists and their patients want to hear, since current recommendations specify that the optimal target level of LDL for cardiovascular benefit should be less than 100mg/dL.

Reducing LDL or "bad" cholesterol is a cornerstone of cardiologists’ efforts to control the epidemic of heart disease, America’s (and the world’s) number one killer disease. Moreover, there has been a recent push to drive optimum LDL levels even lower than are currently recommended. In April 2004, some leading cardiologists called for a target reduction of LDL to 65 mg/dL, to be achieved by taking up to 80 mg per day of Lipitor. Although this recommendation grew out of a study that tested this thesis only in patients with severe cardiovascular disease who were already hospitalized because of a ruptured plaque in their coronary arteries, many doctors were quick to extrapolate these findings to patients in general. "This is really a big deal," Dr. David Waters, a professor of medicine at the University of California in San Francisco, said of these findings. "We have in our hands the power to reduce the risk of heart disease by a lot. It’s very exciting." (New York Times, March 8, 2004).

THE BARKING DOG

Prof. Karas, in an interview with the online medical news service Heartwire, took pains to point out that his research categorically did not indicate that statins cause cancer. The study has established only that there is a correlation between lowered levels of LDL and cancer; no causal link has been demonstrated.

To explain the difference between correlation and causation, Karas coined the analogy of the barking dog. "I have a dog, and every time an airplane goes over my house, my dog goes out into the backyard and barks at the plane. That airplane has never landed in my yard. Now we could say there is a very strong association between my dog barking and planes not landing in my yard, but there certainly is no cause and effect."

In other words, it is the low level of blood LDL that is the concern here, not the use of statins themselves. "What we’re always doing in terms of trying to take care of patients is balance benefit and risk," Karas said. "This analysis was really focused on trying to enhance our understanding of the risk side of that equation. It has produced a provocative and interesting result that raises a lot of new questions... but it’s a complicated message, and the conclusion people will jump to if they are not being careful is that statins cause cancer. We don’t know that, and our data don’t show that."

It can be hard for laypeople to make sense of statements such as this. Confusing correlation with causation is an easy mistake, and one that even physicians commonly make. Let me again emphasize that the Karas study does not show that statins cause cancer. What it does seem to suggest is that low levels of LDL are associated with increased cancer risk.

Yet the primary reason that one takes statins is precisely to lower one’s LDL. So while statins may not be carcinogenic in themselves, their use to push LDL levels below 100 mg/dL - at least according to this one study - seems to be associated with increased cancer risk. If true, this is a ‘damned if you do, damned if you don’t’ proposition. If we assume that levels of LDL below 100mg/dL offer better protection against heart disease, then the more you decrease your risk of heart disease, the more you increase your risk of cancer! And what will happen, long-term, if cardiologists adopt the proposal of some of their peers that optimum LDL be lowered to 65mg/dL or less? Will that lead to a concomitant rise in cancer incidence?

As cardiovascular disease specialist Dr. Thomas Pearson of the Department of Rochester School of Medicine, NY pointed out, it has been known since at least the 1970s - before statins were even invented or LDL became a household term - that cancer risk was heightened in patients with the lowest cholesterol levels. Indeed, conventional medical wisdom at that time said that when a patient’s cholesterol levels were seen to fall significantly over a short period of time, a cancer diagnosis often followed.

While not arguing against the use of statins per se, the Karas study does call into question the assumption that disease can be effectively managed by manipulating one particular biomarker - a biochemical or physiological metric whose relationship to the entire disease process is far from clear. It also points to the necessity of following the effect of drugs long-term, not just for the specific disease that they are designed to treat or prevent, but for their impact on health in general, including cancer incidence and mortality.

HOW LOW SHOULD WE GO?

In an editorial accompanying the publication of the Karas study, Dr. John LaRosa of the State University of New York, Brooklyn, expressed the opinion that the study had focused attention on an issue that urgently needed to be addressed - namely, does the process of lowering LDL, particularly to very low levels, introduce hazards of its own in either causing or accelerating the process of cancer?

In the management of cardiovascular disease risk, statins have undoubtedly been extremely effective for countless patients, and, in the opinion of most cardiovascular specialists, have saved many lives. But the issue of whether it is always beneficial to push LDL levels below 100 mg/dL, much less 65 mg/dL, remains unclear.

If the Karas study stands up to future scrutiny, it may be necessary to rethink current recommendations for drastically lowering LDL in many individuals. Lower may not always be better.

NOTE

An insightful overview of the risks and benefits of statins is available at the University of California, San Diego, Statin Study Group Web site:
http://medicine.ucsd.edu/SES/index.htm

This UCSD site is edited by Beatrice Golomb, MD, PhD, who maintains a database on statins and has published many papers concerning these drugs. One of Dr. Golomb’s most recent papers, documenting the generally dismissive response of physicians to patients’ complaints concerning side effects of statins, was mentioned in a previous issue of this newsletter which you can read by clicking or going to:
http://cancerdecisions.com/093007.html

--Ralph W. Moss, Ph.D.

References:

Alsheikh-Ali AA, Maddukuri PV, Han H, et al. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol 2007;50(5):409-18.

Cauley JA, McTiernan A, Rodabough RJ, et al. Statin use and breast cancer: prospective results from the Women's Health Initiative. J Natl Cancer Inst 2006;98(10):700-7

Coogan PF, Rosenberg L, Strom BL. Statin use and the risk of 10 cancers. Epidemiology 2007;18:213-219.

Coogan PF, Smith J, Rosenberg L. Statin use and risk of colon cancer. J Natl Cancer Inst 2007;99(1):32-40.

Fortuny J, de Sanjosé S, Becker N, et al. Statin use and risk of lymphoid neoplasms: results from the European Case-Control Study EPILYMPH. Cancer Epidemiol Biomarkers Prev. 2006;15:921-925.

Heart Protection Study Collaborative Group. The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomised placebo-controlled trial. BMC Med. 2005;3:6.

Peppercorn J, Blood E, Winer E, et al. Association between pharmaceutical involvement and outcomes in breast cancer clinical trials. Cancer. 2007;109(7):1239-46.

Strandberg TE, Pyorala K, Cook TJ, et al. Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet. 2004;364(9436):771-7.

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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.