FDA Medwatch: Poss Link beween Vytorin and Cancer

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FDA MedWatch- Ezetimibe/Simvastatin (Vytorin); Simvastatin (Zocor); and Ezetimibe (Zetia) - Report Of SEAS Trial Of A Possible Association Between The Use Of Vytorin And A Potential Increased Incidence Of Cancer
               
  
MedWatch logo MedWatch - The FDA Safety Information and Adverse Event Reporting Program

FDA informed healthcare professionals that the Agency is investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of Vytorin and a potentially increased incidence of cancer. Vytorin is a combination product of simvastatin and ezetimibe used to decrease the production of cholesterol by the liver and inhibit the absorption of cholesterol in the intestine to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events. Recently, FDA obtained preliminary results from the SEAS trial. The clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis. A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study.

FDA anticipates receiving a final SEAS study report in about 3 months and the Agency's review and evaluation of the clinical trial data and other relevant information should take approximately 6 months. FDA will communicate its conclusions and recommendations at that time. Healthcare professionals and caregivers should continue to monitor patients taking Vytorin and report side effects from the use of this drug to the Agency.

Read the complete MedWatch 2008 Safety Summary, including a link to the '"Early Communication About an Ongoing Safety Review of Ezetimibe/Simvastatin (marketed as Vytorin); Simvastatin (marketed as Zocor); and Ezetimibe (marketed as Zetia)", at:

http://www.fda.gov/medwatch/safety/2008/safety08.htm#ezetimibe2

gpawelski

Vytorin and Cancer - is there a link?

The New England Journal of Medicine (NEJM) editorial blasted the analysis by Oxford University statistician, Richard Peto that dismissed Vytorin's possible link to cancer. The SEAS study found that Vytorin patients had higher rates of cancer and cancer deaths. The results for cancer incidence was clearly significant, as well as the results for cancer death.

The NEJM editorial on ezatimibe accompanied the publication of the SEAS trial and a statistical analysis of cancer incidence and deaths in SEAS and two other ezetimibe trials conducted by Richard Peto and the Clinical Trials Service Unit of Oxford University.

Vytorin is a combination of cholesterol-lowering Zetia (ezetimibe) and the statin Zocor (simvastin). As mentioned in the NEJM editorial, some have theorized that Zetia could cause cancer because it blocks chemicals called plant sterols, which may cause heart disease but could also have some anti-cancer effect.

Plant sterols (phytosterols) resemble cholesterol in structure but are found exclusively in plant-based foods like fruits, vegetables, nuts and whole grains. A number of tissue culture studies have exposed various types of human cancer cells to plant sterols and have found a slowing of the progression of cells from one stage to another, something that is abnormal in cancer cells.

In addition, plant sterols have been found to cause apoptosis and shown to inhibit changes in cells that take place when tumor cells metastasize. Also, it has been shown an increase in growth of cells that are part of the human immune system, such as natural killer cells, which could be protective against cancer.

Ezetimibe inhibits cholesterol absorption, as opposed to removing cholesterol from the blood like statins. But ezetimibe also inhibits absorpotion of dietary plant sterols and there is a plausible theory that the reduction in sterol absorption in patients in the SEAS trial may have increased risk of contracting cancer.

The SEAS trial found an increase in cancer cases and deaths in the group that received ezetimibe. The Peto analysis of two ongoing ezetimibe trials found no increase in cancer cases, but did find more cancer deaths (97 vs. 72 in the control group), although the increase in cancer deaths did not reach statistical significance (p = .07).

When all three trials (SEAS, IMPROVE-IT and SHARP) were combined, there was a significant excess of cancer deaths among the patients assigned to ezetimibe (134 vs. 92; risk ratio, 1.45; p = 0.007). The Oxford group believes this is a statistical fluke, noting that there was no trend in the relative risk of death from cancer over time in SHARP and IMPROVE-IT alone or in all three trials combined.

Several lines of evidence suggest that plant sterols may have anti-cancer effects. The New York Tiimes interviewed Peter Bradford, a pharmacologist at SUNY Buffalo who has extensively studied plant sterols. Bradford explained that in laboratory tests plant sterols promote cell death in a way that could make them valuable anti-cancer agents as weapons against tumors. But by blocking plant sterol absorption, ezetimibe could be promoting cancer, he said.

More data is urgently needed before patients can again feel comfortable taking ezetimibe. It would be useful for the SEAS investigators to test the levels of plant sterols and carotenoids in blood samples from participants in the SEAS trial.

Until more information is available, ezetimibe use should be limited to patients in clinical trials. Zetia should not be used in clinical medicine until the justifiable and substantial cloud of uncertainty over it is resolved.

gpawelski

More Uncertainty Over Zetia

Zetia is ezetimibe, a component of Vytorin. In the ENHANCE trial, ezetimibe had no effect on atherosclerosis, leading a panel at the American College of Carbiology conference in March 2008 to recommend that it be used only as a last resort. The SEAS trial found a troubling increase in cancer in patients who received ezetimibe, leading to uncertainty as to ezetimibe's safety.

A new study, published in the December issue of the Journal of the American College of Cardiology, added nothing to the knowledge about ezetimibe's safety and efficacy. This study was an analysis of data from the SANDS trial.

This new study is a post-hoc analysis, a term which refers to testing data for patterns that you had not  planned to look for when the study was designed. Sometimes called "data dredging," this technique has been compared to shooting an arrow into a target and then drawing a bull's-eye around it.

In this case, the researchers compared patients who achieved low cholesterol levels with a combination of a statin and ezetimibe with patients who achieved similar levels with a statin alone, and found no difference in the effect on atherosclerosis. However, only 69 patients received ezetimibe and the two groups were not determined through randomization.

Although SANDS was funded by the National Institutes of Health, several of the researchers have close ties to Merck and Schering-Plough, the manufacturers of ezetimibe, having received research support from and served on the scientific advisory boards and/or speaker's bureaus of these companies.

Source: GoozNews

http://cancerfocus.net/forum/showthread.php?t=233

Rosemary44

This makes me feel happy that I gave up Zetia.  Drs. are getting paranoid about getting LDL cholesterol under 70 for certain high risk people.  Zetia will do that.  Where is the evidence that it is necessary to have LDL under 70?  Now there's a possible cancer connection?  Maybe it's not good to have such low LDL.  Or maybe its the pill itself causing the problem.  One thing is for sure they should find out.

Harley44

Now I am wondering...  do they know if ALL the cholesterol-lowering medications can cause cancer?

My FIL took Zocor for MANY years, and then he got kidney ca, with mets to the bones.  I often wondered if the cholesterol medication had anything to do with him getting ca.

Harley

Rosemary44

Harley,

I think we're going to stay wondering.  They sell billions of dollars worth of cholesterol lowering drugs.  It's the last thing they'll do is to look at them closely.

Harley44

Rosemary,

Ain't that the truth?  Sad, but true.  As long as they are making money hand over fist on these drugs, we won't see them doing a study to see what the long term se's might be.

I think I will try to control my borderline cholesterol levels with exercise and supplements.  Here is yet another question for my onc when I see him on Friday, not that he will have any answers for me, but at least I know that he won't side with the drug companies...  He's a rather blunt guy, and I think he will level with me.  The problem is that he will probably say that they just don't know...

Oh, and I agree with you completely about the LDL not needing to be under 70.  My sister has Graves Disease, and at one of our regular gatherings, my other sisters and I were mentioning our high cholesterol levels.  She just looked at us and said that her cholesterol has NEVER been a problem, in fact, it was LOW....    I have read that  LOW cholesterol is a symptom of certain diseases, and Graves Disease is one of them.  Go figure!

Harley

gpawelski

Don't forget, ezetimibe inhibits cholesterol absorption, as opposed to removing cholesterol from the blood like statins. But ezetimibe also inhibits absorpotion of dietary plant sterols and there is a plausible theory that the reduction in sterol absorption in patients in the SEAS trial may have increased risk of contracting cancer.

Ezetimibe does not reduce production of rho kinase (the substance that increases vascular inflammation) and in fact may increase it. May that explain why ezetimibe (Zetia) and Zocor, which is Vytorin, causes allergic reactions including inflammation of the pancreas and inflammation of the gallbladder?

Some studies have indicated that it may in fact not be the cholesterol reduction that leads to the positive results demonstrated by these drugs, but rather the blood (and cellular) changes precipitated by this drug that may be the cause of not only the sinister body chemistry changes but the demonstrated cancer causing potential.

Until more information is available, ezetimibe use should be limited to patients in clinical trials. Zetia should not be used in clinical medicine until the justifiable and substantial cloud of uncertainty over it is resolved.