Is there a role for statins in oncology?

Resource post for February

Statins or HMG-CoA reductase inhibitors are pharmacological agents used in the control and management of hyperlipidemia or high cholesterol levels. The most popular statins are Lipitor (atorvastatin) and Zocor (simvastatin).

According to the US Food and Drug Administration (US FDA), statins work in the liver to prevent formation of cholesterol

• are effective in lowering bad cholesterol levels and raising good cholesterol
• are not recommended for pregnant patients or those with active or chronic liver disease 
•  can cause serious muscle problems

Currently available statin drugs are:

• Lovastatin (Mevacor, Altoprev)
• Pravastatin (Pravachol)
• Simvastatin (Zocor)
• Fluvastatin (Lescol)
• Atorvastatin (Lipitor)
• Rosuvastatin (Crestor)

Several studies in recent years indicate that the use of statins can go beyond the therapeutic area of cardiovascular medicine. One of the therapeutic areas is oncology and here are some of the studies:

Statins lower blood marker for prostate cancer

The study tracked 1214 men who were taking statins between 1990 and 2006 and monitored the levels of prostate-specific antigen (PSA), a known biomarker for cancer risk. Those who were on statins had lower PSA levels and effect of statins on PSA was dose-dependent. Whether the effect of statins on the PSA levels translates into anticancer properties is not yet clear. It is also not clear statins interact with prostate biology. However, the anti-inflammatory properties of statins may play a role.

Statins lower risk of clots in cancer patients

Researchers at the Albert Einstein Medical Center in Philadelphia reported statins lower the incidence of blood clots in cancer patients. It is possible that statins “may have a future in preventing blood clots in patients with breast, lung, colon and other solid-organ cancers…Statins could improve endothelial function, and this could reduce the chance of venous thrombosis. Conceivably, statins could have some benefits on clotting factors. It is known that statins can have platelet effects, but this should help arterial thrombosis and would not be expected to help venous thrombosis.” Blood clots in the form of venous thromboembolism (VTE) are conditions that results when patients stay immobile for long periods of time (e.g. after surgery).However, the results are very preliminary and need to be confirmed in bigger studies.

Breast cancer and statins

A more recent research, however, demonstrated that statins do not prevent cancer. This was published in an article in the February issue of the American Association for Cancer Research (AACR) journal Cancer Prevention Research.

The results of previous studies on breast cancer and statin were a bit controversial, even inconclusive because they were mostly restrospective studies, e.g. studies that look at data in retrospect. In clinical research however, prospective studies carry more weight when it comes to providing evidence.

The current study compared the effectiveness of statins atorvastatin and lovastatin in laboratory animals with proven anti-tumor drugs on preventing breast tumors.

Atorvastatin orally administered at a dose of 125 and 500 mg/kg body weight did not influence the incidence of estrogen receptor-positive or estrogen-receptor negative breast cancers in mice. Similarly, lovastatin orally administered at 100 and 500 mg/kg body weight also did not show any significant effects. In contrast, 0.4 mg of tamoxifen or 80 mg of bexarotene induced a significant reduction in the multiplicity of mammary tumors. Combining statins with the anti-tumor drugs did not show any augmentation effect.

According to researcher Dr. Ronald Lubet

“We saw no real efficacy from either statin…Prior studies have shown some but limited efficacy in breast cancer models when these drugs were given through a method that would be the equivalent of intravenously in humans. However, that is not the way people take statins… There is always the question of whether there will be a subset of breast cancer where this class of agents will be effective, but the answer at this point is that the present preclinical studies do not support the use of statins as general breast cancer preventive agents.”

Statins are the blockbusters of the pharmaceutical industry, earning billions of dollars in revenues. One the most successful statins is Lipitor (atorvastatin) of Pfizer, supposedly the bestselling drug globally. However, many popular drugs have gone or are about to go off patent, thus exposing big pharma companies to competition from generic companies. Lipitor goes off patent in 2011. Finding new therapeutic applications for statins could be a way for many big companies to keep their hold on their bestsellers.

Some people might think that pharmaceutical companies are simply clutching straws when testing statins in other therapeutic areas. I believe this is not so. The wonder drug aspirin (acetylsalicylic acid), for example, was initially developed to treat fever and headaches. Nowadays, it occupies a major role in cardiovascular medicine as an anticoagulant agent and is also being tested in treating different kinds of cancer. Another blockbuster drug, Viagra, was initially developed as a cardiovascular drug before its rather “profitable and beneficial” side effect” was discovered.

               

Knowing your heart and stroke drugs: statins

Resource post for November

Background

Statin drugs or HMG-CoA reductase inhibitors play a very important role in the prevention of cardiovascular diseases. They are the first line treatment against high cholesterol levels. Statins have anti-inflammatory properties and interfere with the production of cholesterol thus slowing down the formation of plaques on the arterial walls.

According to the US FDA, statin medications

• work in the liver to prevent formation of cholesterol
• are effective in lowering bad cholesterol levels and raising good cholesterol
• are not recommended for pregnant patients or those with active or chronic liver disease
• can cause serious muscle problems

Statins are also said to be the bestselling drugs of all times, raking in billions of dollar in sales every year. Currently available statin drugs are:

• Lovastatin (Mevacor, Altoprev)
• Pravastatin (Pravachol)
• Simvastatin (Zocor)
• Fluvastatin (Lescol)
• Atorvastatin (Lipitor)
• Rosuvastatin (Crestor)

Research studies

Recent studies indicate that statins may play a major role in therapeutic areas outside cardiovascular medicine, thus may earn the title of “the aspirin of the 21st century“. Some of these studies are summarized below.

Statins associated with lower risk of death from pneumonia

Pneumonia is a major cause of mortality worldwide, even in developed countries. It has been reported that the incidence of pneumonia is increasing and hospitalization rates in the US and Europe have increased by 20 to 50% during the last 10 years. About 10 to 15% of pneumonia cases result in death.

Does statin use lower mortality rates due to pneumonia? Danish researchers report in the October 27 issue of Archives of Internal Medicine that “individuals who take cholesterol-lowering statins before being hospitalized with pneumonia appear less likely to die within 90 days afterward.”

The researchers studied data from 29,900 patients hospitalized with pneumonia between 1997 and 2004. 4.6% of these patients (1,371) were taking statins before and during hospitalization as anticholesterol treatment.

Death rates within 30 days among statin users were much lower (10.3%) were much lower than non-statin users (15.7%). The same trend was observed after 90 days, with 16.8% mortality rates among statin users compared to 22.4% among non-users.

The mechanism behind this effect of statins is not clear but the authors theorize that

“Statins change the immune response, beneficially affect processes associated with blood clotting and inflammation and inhibit dysfunction in blood vessels. These effects may especially benefit patients with sepsis and bacteremia, which are associated with early death from pneumonia.”

Statins block 1 cause of pregnancy loss in mice

What does statin have to do with pregnancy? Researchers at Cornell University observed that statins can actually prevent antiphospholipid syndrome (APS), an inflammatory condition that causes serious complications in pregnancy ranging from spontaneous abortion, fetal growth problems and even fetal death. The researchers demonstrated this beneficial effect of statins in laboratory mice.

Statins may protect against memory loss

Statins seem to also have protective properties against dementia and other neurodegenerative diseases. This is according to a study by researchers at the University of Michigan School of Public Health. The researchers observed that “if a person takes statins over a course of about 5-7 years, it reduces the risk of dementia by half.” The study studied tracked 1674 older Mexican-Americans did not have dementia for 5 years. Within the follow up period, 130 study participants developed some form of dementia or cognitive impairment. The incidence of dementia was lower among the 452 participants who took statins at some point in the study. This is an interesting development in view of stories about the popular statin drug Lipitor causing memory losses.

Statins lower blood marker for prostate cancer

Men who are taking statins to lower their cholesterol levels have lower prostate-specific antigen (PSA). PSA is a known biomarker for cancer risk. The PSA reduction seems to be related to statin use in a dose-dependent manner. The study followed up 1214 men who were on statins between 1990 and 2006 and monitored their PSA levels. Whether the effect of statins on the PSA levels translates into anticancer properties is not yet clear.

Are statins beneficial or harmful in multiple sclerosis?

A previous study in animals has shown that some statins may be beneficial against multiple sclerosis when combined with other drugs. This was demonstrated by University of California researchers in mice. In another study, Phoenix researchers showed that simvastatin may have some anti-inflammatory effect that counteracts inflammatory components of multiple sclerosis. However, another study indicates that certain doses of stains combined with beta interferon may actually increase the clinical disease activity in patients with multiple sclerosis. “Caution is [therefore] suggested in administering this combination.” The latter study was based on data of 26 study participants.

Statins lower risk of clots in cancer patients

Researchers at the Albert Einstein Medical Center in Philadelphia observed that cancer patients taking statins have lower incidence of blood clots than non-users. Thus, statins “may have a future in preventing blood clots in patients with breast, lung, colon and other solid-organ cancers.”

Caveat

The abovementioned studies show that there are other potential uses of statins aside from lowering cholesterol levels. However, all these results are preliminary. Further and larger studies are needed to further explore these beneficial effects as well as the risks that may be involved. Many people will claim that most of the positive reports about statins are propaganda from the pharmaceutical companies. Conspiracy theories abound. However, if statins can provide health benefits beyond cardiovascular medicine, who are we to say no?

We also have to be aware that like all drugs, statins come with side effects. Most side effects are mild but some can be serious. Myopathy is a potential fatal denegerative disease of the muscles possibly linked to statin use.

Photo credit: stock.xchng

               

STATINS TO HELP MS

17 March 2006

A DRUG to lower cholesterol could also help multiple sclerosis sufferers, say researchers.

Tests on mice with a similar auto-immune condition produced remarkable results when cholesterol busting statin Lipitor was combined with MS drug Copaxone.

It helped prevent or reduce paralysis, said scientists at the University of California and Stanford University Medical Center in California.

Team member Dr Olaf Stuve said: “It represents a potential new strategy for treating MS.” The MS Society said: “These are promising results.”

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