Life Extension Magazine February 2014

Report

Brain Tumor Treatment Breakthrough!

By William Faloon and Lisa Antone

Bio-Enhanced TURMERIC Compounds Block Multiple Inflammatory Pathways  

Perhaps the most frightening malignancy one can be diagnosed with is a form of brain cancer called glioblastoma multiforme.

This type of brain cancer has a dismal prognosis, with median overall survival of 12 to 15 months, and a 2-year survival rate of 15% to 26%.1

You may remember that Senator Ted Kennedy was diagnosed with glioblastoma multiforme in May 2008. Despite intervention by brain tumor experts, Sen. Kennedy died in August 2009 — a mere 15 months later.

We at Life Extension® have long-been evaluating new approaches to treat this deadly malignancy. We’ve been frustrated by the paucity of meaningful progress and our inability to make better treatment recommendations.

A study published in the September 5, 2013 edition of the New England Journal of Medicine may represent the most significant advance yet discovered in treating glioblastoma multiforme.

What follows is an overview of this therapy that is available right now to brain tumor patients:

  • The cytomegalovirus has been suspected as facilitating the initiation and promotion of brain cancers.2-4 From 50% to as many as 80% of adults in the United States show exposure to cytomegalovirus, but relatively few harbor active viral infection.5
  • Doctors followed 75 glioblastoma multiforme patients and found the median overall survival of those withlow-grade cytomegalovirus infection was 33 months. In patients with high-grade cytomegalovirus infection, median overall survival was only 13 months.1
  • All but one of the 75 glioblastoma multiforme patients studied had active cytomegalovirus infection, indicating that this virus may be involved in the development of this lethal malignancy. 1
  • In glioblastoma multiforme patients with high-grade cytomegalovirus infection, median 2-year survival was 17.2%. Patients with low-grade cytomegalovirus infection had median 2-year survival rates of 63.6%. This suggests that high-grade active cytomegalovirus infection accelerates tumor progression. 1
  • Valganciclovir (Valcyte ® ) is an FDA-approved drug used to treat cytomegalovirus infection. 1
  • In a double-blind clinical trial of valganciclovir involving 42 patients with glioblastoma, an exploratory analysis of 22 patients receiving at least 6 months of antiviral therapy showed 50% overall survival at two years compared with 20.6% of contemporary controls. This study showed that valganciclovir-treated patients have a median overall survival of 24.1 months compared to 13.7 months in patients not treated with valganciclovir. 1
  • Owing to the promising results of this pilot study, glioblastoma multiforme patients at the world famous Karolinska University Hospital received valganciclovir and results were then compared to a control group. Both groups received standard conventional therapy and both groups had a similar disease stage and surgical-resection grade. 1
  • The researchers retrospectively analyzed the data on 50 of these brain cancer patients and found the 2-year rate of survival in the valganciclovir group was 62%, whereas 2-year survival was only 18% in the control group. 1
  • In 40 glioblastoma multiforme patients who received valganciclovir for at least 6 months, the 2-year survival rate was 70%, with a median overall survival of 30.1 months. 1
  • 25 glioblastoma multiforme patients that received continuous valganciclovir treatment after the first 6 months had a 2-year survival rate of 90%, with median overall survival of 56.4 months (4.7 years)! 1
  • Recall that current median survival of glioblastoma multiforme patients is only 12–14 months. 1
  • Also recall the efforts made to prolong Sen. Kennedy’s life and the best the experts at Duke University Medical Center could do was 15 months.1

The implication from these findings is that treating active cytomegalovirus infections may dramatically reduce progression, and significantly increase survival time, in patients suffering from the deadly brain cancer glioblastoma multiforme. Most exciting is the intriguing data from this retrospective study that valganciclovir treatment in patients with active cytomegalovirus produced an unheard of median survival of 56.4 months (4.7 years) in glioblastoma multiforme patients.1

Not only does this retrospective data involving the continuous use of valganciclovir extend survival in glioblastoma multiforme patients, but it provides an opportunity to add in additional complementary therapies (like metformin) that could improve outcomes even more!

What Brain Tumor Patients Should Do

What Brain Tumor Patients Should Do  

At the time of surgical resection of the brain tumor, a specimen should be sent for immunohistochemical analysis to evaluate presence and activity of cytomegalovirus.

In glioblastoma multiforme patients with evidence of cytomegalovirus-positive tumor tissue, those who wish to follow the protocol that resulted in unprecedented survival improvements should consult with their oncologist and consider 900 mg of valganciclovir twice a day for three weeks followed by a maintenance dose of 450 mg twice a day indefinitely to be adjusted for side effects such as kidney impairment and bone marrow suppression.1

Valganciclovir should be taken with fatty meals to enhance its absorption/bioavailability.

The price of valganciclovir is beyond outrageous, with the annual cost being around $50,000.

Those who have already had surgery should have their blood tested to help determine cytomegalovirus activity. Patients whose blood test reveals active cytomegalovirus (CMV) infection, which appears to be an important risk factor in some glioblastoma multiforme patients, should have the cost of valganciclovir covered by their medical insurance.

Cancer patients can often have blood tests covered by their medical insurance as long as their oncologist prescribes the tests.

Will Historic Human Carnage Repeat?

Will Historic Human Carnage Repeat?  

Glioblastoma multiforme is a death sentence. Virtually no one survives long-term. It kills 12,000 Americans each year and many more throughout the world.

The findings from this study showing vast survival improvement in brain cancer patients were published in the prestigious New England Journal of Medicine. Previous published studies corroborate the role that cytomegalovirus may have in human cancers and the potential benefit of valganciclovir.

Since 1980, Life Extension has been at the forefront of identifying off-label cancer drugs like cimetidine, aspirin, and metformin, but medical authorities largely ignore us. When properly used, there is intriguing evidence that suggests metformin, aspirin, and cimetidine could spare tens of thousands of Americans from agonizing cancer deaths each year, yet virtually no oncology group routinely prescribes them.

The benefits reported in the New England Journal of Medicine represent the most significant survival advance against this deadly brain malignancy in history, yet these findings were virtually ignored by the mainstream media even though the life-sparing drug (valganciclovir) is available right now.

It is illegal for the maker of valganciclovir to promote it as a treatment for brain cancer. The regulatory system in the United States requires that the maker of a drug conduct extensive clinical trials for each disease a drug is claimed to treat and then submit the trial results to the FDA for approval.

While it is legal for doctors to prescribe valganciclovir off-label—that does not protect a doctor’s medical license if a patient has an adverse reaction. So many oncologists may refuse to prescribe valganciclovir despite findings that it may improve survival of glioblastoma multiforme patients more than three-fold.

So there is the real possibility 12,000 Americans will continue to perish from glioblastoma multiforme each year despite impressive findings showing that valganciclovir could spare many of them from premature death.

Glioblastoma multiforme patients whose tumor specimen reveals immunohistochemical evidence of active CMV infection, or whose blood test is CMV positive for active infection, should ask their oncologist to consider valganciclovir.

My greatest concern is that this valganciclovir study published in the New England Journal of Medicine will be relegated to medical archives and not be utilized to save cancer patients, just as hundreds of published studies on metformin, aspirin, and cimetidine have been ignored by the medical establishment for the past four decades.

The article on the next page provides a more in-depth review of the role that CMV infection plays in the development and progression of brain and other cancers.

For longer life,

For Longer Life

William Faloon

Common Virus Linked to Deadly Brain Cancer

By Lisa Antone

Few people would ever suspect that one of the most deadly forms of brain cancer is caused by a common virus carried by the majority of people. Yet that’s exactly the case, according to a number of new studies in prestigious medical journals.

In the same way that cervical cancer and head and neck cancer has been linked to certain strains of the HPV virus, the most common and deadly type of brain cancer, glioblastoma, has been linked to a virus in the herpes family called CMV (short for cytomegalovirus).6,7

A diagnosis of glioblastoma means certain death, with population studies indicating typical overall survival rates of less than a year.8 And unfortunately, this deadly form of brain cancer is the most common malignant brain tumor in the US.8

Establishing a link between this deadly cancer and a common virus is an enormous step in understanding how to treat, and potentially to prevent, early and unnecessary deaths. And more importantly, it led to the discovery of a drug that can quadruple the life span of those who have already been diagnosed with this deadly disease!1

What You Need to Know

CMV And Brain Cancer: The Deadly Connection

  • The deadly brain cancer, glioblastoma, has now been convincingly linked to a common virus, cytomegalovirus (CMV).
  • Most people are infected with CMV, but latent disease carries no symptoms.
  • Strong evidence suggests that CMV lying latent can become reactivated and trigger cancerous growth in the brain and other organs.
  • A dramatic pair of recent studies shows that treating CMV in glioblastoma patients significantly prolongs survival, nearly doubling it at 6 months and more than quadrupling it with prolonged treatment.
  • Antiviral drug treatment, however, is not for otherwise healthy people; it is hideously expensive and produces major side effects.
  • But healthy people can take major steps: get tested for CMV, and then start one or more of the supplements known to support healthy immunity and resistance to re-activation of CMV.

The Dangers Of The CMV Virus

Cytomegalovirus, or CMV, may be the most important virus you’ve never heard of. The prevalence of latent CMV infection is up to100% in most populations of adults worldwide with increasing prevalence in the elderly, and is now considered to play multiple roles in immunosenescence, the gradual fading of immune function with age.9,10

This is a serious problem. Latent CMV infections are strongly associated with frailty in the elderly and dramatically increases mortality risk.11,12 CMV has also been associated with accelerated aging in general, and even with shortening of telomeres (the age-regulating bits of DNA that govern each cell’s lifespan).13 Indeed, a 2013 study found disturbing early signs of immunosenescence in young people who tested positive for CMV, compared with their CMV-negative peers.14

And of course, waning immune function also opens the door for cancers to develop, freed of the ever-present surveillance carried out by a younger, more robust immune system.

And that’s just with the latent form of the virus; the active form is far worse. Active CMV disease in older patients or in those with compromised immune systems is a devastating disease. It can cause hepatitis leading to liver failure, retinitis leading to blindness, severe colitis (large bowel inflammation), pneumonitis (viral pneumonia), esophageal inflammation, and disorders of the central and peripheral nervous systems.15,16

But unlike other herpes viruses, CMV rarely produces detectable symptoms in otherwise healthy people.16 That makes it difficult to diagnose, and dangerously easy to spread. Diagnosing CMV often requires two separate blood tests, several weeks apart, as well as a high index of suspicion by both patient and provider (see sidebar on the next page for an understanding of test results).17 CMV spreads the way other herpes viruses do: by contact with bodily secretions, especially saliva.18

The ease of spread and the absence of symptoms in healthy adults accounts for the very widespread prevalence of CMV.18 Estimates vary, depending on geography, socioeconomic status, and other variables, but at least 35%, and up to 100% of people in some communities, will test positive for CMV.19-21

Life Extension Magazine February 2014

Report

Brain Tumor Treatment Breakthrough!

By William Faloon and Lisa Antone

CMV: The Cancer Connection

Over the past decade, scientists have become increasingly concerned at the growing association of CMV with certain cancers. While it is too early to label CMV a true cancer-causing virus,22 evidence implicating CMV as a contributor to cancer comes from several observations:

  • Studies show a strong correlation between cancer incidence and the percentage of adults who test positive for CMV.23,24
  • CMV proteins and DNA have been found in 90-100% of malignant cells from a variety of cancers, especially those of the brain, breast, prostate, liver, lung, and colon.1,25-33
  • CMV genes, once inserted into the host’s own DNA, increase inflammation-generating genes that promote cancer growth.34,35
  • CMV genes are known to induce mutations in host tumor-suppressor genes, increasing the risk that a new cancer will develop.36
  • CMV may help cancer cells avoid detection by the immune system by several mechanisms including increased secretion of immune suppressive cytokines.22
  • CMV-infected cells produce more of the growth factors and chemical receptors needed for tumor development and invasion, compared to non-infected cells.32,33,37

The evidence for a direct connection between CMV and malignancy is by far the greatest in the case of the deadly brain tumor called glioblastoma multiforme (often simply “glioblastoma”). This tumor is the most common and aggressive brain cancer, and it carries a dismal prognosis.38,39

Most patients die within the first 15 months of diagnosis, with few surviving past 3 years.40-42

Glioblastomas occur most commonly in the frontal and temporal (side) lobes of the brain, where they produce disturbing symptoms that include persistent headaches, double or blurred vision, vomiting, changes in mood and personality, changes in cognition, seizures, and speech difficulty.42

In addition to their aggressive growth, glioblastomas are notoriously difficult to treat because of their location within the brain, where efforts to extract them are complicated by their deep invasion of healthy brain tissue and the brain’s limited ability to repair itself.40,42 Patients with glioblastomas frequently experience a number of clinical complications including seizures, blood clots, fluctuating neurological symptoms as well as side effects from powerful corticosteroids and chemotherapeutic drugs.43

Glioblastomas leak fluid, increasing the pressure on brain tissue; they also disrupt the blood supply, making it difficult for anti-cancer drugs to reach them.42

All of this accounts for the fact that, despite three decades of research, we have managed to increase overall survival in cases of glioblastoma by only about 3 months.42,44 Making matters worse, the tumor strikes at the prime of life, occurring mainly in adults between 45 and 70, with a median age at death of 64 years.42

The high incidence of glioblastoma, coupled with the difficulty of its treatment, has made the search for causes and preventive measures paramount. That’s why this emerging evidence about the link between CMV and malignant brain tumors is exciting to so many researchers.34

Testing Your Blood For CMV

Cytomegalovirus (CMV) is part of the herpes virus family, which means that this virus is almost never completely cleared from the body following infection.77 The maintenance of suppression of viral infection is dependent upon a strong immune system.

Cytomegalovirus can lie dormant in your body for decades before emerging in response to a weakening of the immune system.77

The steps that aging Life Extension members take to protect against immunosenescence such as maintaining youthful levels of DHEA, suppressing oxidative stress, and taking immune boosters like garlic and reishi mushroom extracts should help keep cytomegalovirus in check. But each individual is different, and reemergence of CMV infection is often asymptomatic in normally aging people.

The regular member price for the blood test called CMV IgM that detects acute, initial cytomegalovirus infection is $125. The antibody test for past/prior infection is called CMV IgG and it normally costs Life Extension members $59. We’re making both of these tests available to members for a limited time for only $169. When calling about this, please mention code: BTA422D so the operator knows to give you this special price.

If you order any CMV tests, we’ll include at no additional charge, a comprehensive blood count and blood chemistry test that includes glucose, cholesterol, LDL, HDL, triglycerides, liver-kidney, immune cell counts, and many other tests.

To ascertain if you have evidence of acute, initial, or past/prior cytomegalovirus infection, you should order both the CMV IgM and IgG tests. At the discounted price of $169 plus the free CBC/Chemistry panel you save $50 compared to if all three tests were ordered separately. When ordering these tests, call 1-800-208-3444 (24 hours). Please mention code: BTA422D.

Understanding Your CMV Test Result

The most-commonly used test for CMV is a blood test looking for evidence that your body has encountered the virus. The test for prior infection looks for the antibody called IgG. If it is negative, you don’t have (and never had) CMV infection.77

If the IgG test is positive, however, it only indicates that your body has, at some time in the past, been invaded.77 It means the virus is still latent in your body, but is not active at present. To identify active infection, you need to test your blood for the antibody called IgM.77

If you test positive for IgM, you may be recently infected with CMV, or you may recently have been re-exposed to the virus. Or, your body may be experiencing re-activation of the virus as a consequence of immunosenescence or another cause of reduced immunity. But IgM alone is not used to diagnose active CMV infection.77

Instead, test for both IgG and IgM. If both are negative, your body has never seen CMV. If IgG is positive, and IgM negative, you’re carrying the virus but it isn’t active. If both are positive, it suggests either a recent first-time exposure to CMV, or a reactivation of a latent infection. In this case you can confirm the result with an additional IgG test in 4-6 weeks. A 4-fold or greater rise in IgG level makes it near-certain that active CMV infection is going on in your body and valganciclovir drug therapy should be considered.78

If you have questions, call a Life Extension Health Advisor at 1-866-864-3027.

Strong Link Between CMV And Brain Cancer

There are a number of lines of evidence closely linking CMV with glioblastomas specifically, as well as to cancer in general. Virtually all glioblastomas have been found to contain CMV particles, proteins, and DNA (in one study of 250 patients, only one was CMV-negative).1,2,45 In fact, the amount of CMV in a glioblastoma is closely correlated with the tumor stage: More advanced tumors contain more CMV.22 Recent studies show that the amount of CMV in a tumor can accurately predict survival time in glioblastoma victims, with those carrying the most virus dying significantly earlier (average 13 months) than those with lower viral burden (average 33 months).45,46

Ironically, and tragically, further evidence of CMV involvement in glioblastoma comes from treatment misadventures with the cancer chemotherapy drug temozolomide. This drug, one of the few approved for treating glioblastoma, is powerfully immunosuppressive.47 In glioblastoma patients being treated with temozolomide, reports are now appearing of the emergence of active and devastating CMV disease, indicating that the virus had lain dormant until the patients’ immune systems were suppressed by this chemo drug.47,48

There’s a glimmer of hope on the horizon, however, the direct result of our understanding of the CMV/glioblastoma connection.

Antiviral Drug Quadruples Life Span!

Results of Valganciclovir Treatment in Glioblastoma Patients  

Researchers at the internationally acclaimed Karolinska Institute in Sweden recently made medical headlines with their findings about the use of an antiviral drug quadrupling the lives of patients with glioblastomas.1 The drug, valganciclovir, is widely used in treatment of active CMV infection in immunocompromised patients.

Beginning with an animal model, the researchers found that they could reduce the growth of medulloblastomas (the main group of brain tumors to which glioblastomas belong) by 72% using a drug combination including valganciclovir to combat CMV infection.34

Next, they wanted to determine how effective valganciclovir would be as an add-on to chemotherapy. In a double-blind clinical trial, researchers gave valganciclovir to 42 glioblastoma patients already receiving standard chemotherapy.49 Although tumor sizes were smaller in treated than in non-treated patients, the difference was not statistically significant. There were no significant differences in survival over the 6 months of the study period.

However, that all changed when patients were allowed to continue taking the drug after the study phase. Analyses showed that patients taking valganciclovir for longer than 6 months had an overall survival of 24.1 months, compared with just 13.1 months (a typical survival time) in patients taking the drug for 0 to 6 months.49 By 4 years (an eternity for glioblastoma patients), 27.3% of long-term valciclovir patients survived, compared with just 5.9% of controls.

Encouraged by these results, the researchers immediately undertook another study, again providing valganciclovir as add-on to regular chemotherapy—but this time, extending the study period beyond the original 6-month time frame.1 Fifty patients were treated and compared with controls who received only standard care. In the authors’ own words, “The rate of survival of treated patients was remarkably high”—an understatement considering the facts. Take a look:

  • At 2 years, 62% of all treated patients were still alive, compared with just 18% of controls with comparable cancers.1 Median overall survival was 25 months, vs. 13.5 months in controls (Figure 1a).
  • Among those who received at least 6 months of valganciclovir, the 2-year survival rate was 70% and median overall survival was 30.1 months (Figure 1b).1
  • And, among the 25 patients who received continuous valganciclovir treatment after the first 6 months, 90% of patients were alive at 2 years, and median overall survival was an incredible 56.4 months—that’s more than 4½ years, or a 4.2-fold increase over the 13.5 months in control patients.1 (Figure 1c)

In other words, even short-term treatment with valganciclovir nearly doubled overall survival time; medium-term therapy nearly tripled survival time, and long-term, continuous therapy more than quadrupled it.

These are compelling results. At this point, anyone with a diagnosis of glioblastoma and a desire to extend their lives as much as possible should demand therapy with oral valganciclovir, at 900 mg/day twice daily, followed by a maintenance dose of 450 mg twice daily, with adjustments as needed for impaired kidney function and bone marrow suppression.

What About The Rest Of Us  

What About The Rest Of Us?

As exciting as the results of this study were for those battling glioblastoma, valganciclovir is prohibitively expensive to use as a preventive drug. It can cost upwards of $50,000/year and has myriad side effects, including plummeting white blood cell counts.50

There are no known drugs or supplements that can prevent primary infection with CMV in humans. However, if you are CMV-positive (like so many Americans), there are a number of ways you can protect yourself against the effects of the virus, including protecting against immunosenescence, the immune aging that triggers CMV activation.

Fight CMV-Related Immunosenescence Naturally

Although no human data exist yet, there’s striking evidence that certain natural compounds can inhibit the replication and spread of CMV in animal and basic lab studies.

These include Urtica dioica (stinging nettle), garlic extract, Terminalia chebula (an Asian tree), ginger extracts, flavones from ginger-like Kaempferia parviflora, a variety of seaweed extracts, and oil from Nigella sativa (black cumin seed).51-58 Black cumin seed oil in particular was so effective in mice that, after 10 days of treatment, no virus was detected in treated animals, while it was readily detectable in control mice.55

Other nutrients can fight the CMV that may already be in your body by enhancing your immune system’s resources to fight CMV, as well as other infections that arise when immunosenescence sets in. These include the following:

  • Probiotics and prebiotics, by balancing the intestinal microbial population, have powerful immune-stimulating properties.59,60 Studies show that probiotic/prebiotic therapy produces improvements in natural killer cell activity, activated T-lymphocytes (including “memory” cells responsible for recognizing old enemies), and cell signaling molecules called cytokines.61-64
  • Elderly people are more likely to be deficient in zinc, a trace element absolutely required for normal immunity.65 Zinc supplementation fights immunosenescence by enhancing the appropriate immune response to stress in older humans and by increasing appropriate cytokine signaling to mobilize response to infection.66,67
  • Sulfur-containing antioxidants such as N-acetylcysteine help replenish the body’s normal stores of natural antioxidants, which helps keep immune system cells fresh and vigorous. These supplements improve white blood cell function, increasing their ability to track and attack invaders, and increasing white cell proliferation in response to invasion.68 Aged mice fed a diet rich in N-acetylcysteine and thioproline for 5 weeks showed an improvement in all immune functions, with values becoming close to those of young adult animals.69
  • Spirulina, a blue-green algae, increases the microbe-eating activity of white blood cells called macrophages, while stimulating antibody production and activating killer T-cells that destroy viruses and fungi.70-72
  • Finally, the prescription drug metformin (which is in fact a natural derivative of the French lilac) has shown great promise in reducing immunosenescence and fighting CMV and CMV-related cancers.73 Metformin has shown surprisingly beneficial results in combination with standard treatments for breast cancer,74 and is now being closely investigated as an additional treatment for glioblastoma. Similar studies showed that metformin inhibits growth and migration of glioblastoma cells, a property that would reduce the tumor’s invasiveness in patients’ brains.75 Excitingly, metformin has now also been shown to promote differentiation of glioblastoma-initiating cells into non-cancer-producing cells in lab cultures.76

Life Extension Magazine February 2014

Report

Brain Tumor Treatment Breakthrough!

By William Faloon and Lisa Antone

Summary

Recent research has established a surprising connection between a common virus, CMV, and a deadly brain tumor, glioblastoma. This relationship opens the door to a variety of forms of treatment and prevention of brain and other cancers.

At present, even with chemotherapy, survival in glioblastoma patients is rarely more than 15 months after diagnosis.42

But CMV proteins and DNA are found in the vast majority of glioblastomas removed at surgery, and the amount of CMV has been found to correlate closely with the severity of the tumor.1,2,22,45 This suggests that anti-CMV treatment might ameliorate glioblastoma and improve prognosis.

Indeed, treatment with valganciclovir, a specific anti-CMV drug, has been shown to dramatically increase overall survival in two studies of glioblastoma patients—as much as quadrupling life span!1,49

However, for those with the CMV virus, but without glioblastoma, there are a few supplements that may help fight CMV infection and can mitigate its impact on your body.51-58

You should consider being tested for CMV, by means of a blood test described in the sidebar on page 2. If you test positive, then start some of the recommendations made in this article.

The comforting news for Life Extension® members is that they have been supplementing with immune boosting nutrients for many decades.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

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