Category: News

Research on use of statins in cancer

Our nurses have recently received several questions related to statins, one of the medications in the COC Protocol. The following section of our January 2021 newsletter discusses the research literature relating to statins in the context of cancer and addresses some issues raised by a particular journal paper some patients have enquired about.

Statin safety profile

Statins have a good and well understood safety profile in humans. Like all medicines, they may give rise to side effects in some patients, but most people tolerate them well and do not have any problems. Patients often express concerns about the possibility of statin-induced muscle pain, but the actual risk is about 5% or less compared with placebo (a pill that does not contain any medication). Incidence of liver adverse reactions is also quite rare, at less than 2%.

The fact some level of risk exists is precisely why Care Oncology checks bloodwork at baseline and at regular intervals, and monitors for possible side effects. Our team will adjust the dose of statin or pause it if we become aware of any concerns. And of course, we take the same approach with all the other COC protocol drugs too.

Care Oncology’s clinical experience with our patients to date is in line with the risk profile outlined above i.e. the vast majority can tolerate statins without any issues. Blood cell counts and organ function abnormalities are most frequently linked to chemotherapy and/or other conventional care treatments which carry a greater toxicity risk than any of the COC Protocol medications.

Research on use of statins in cancer

Very large numbers of cancer patients take both a statin and metformin for management of other long-term health conditions and need to remain on these drugs for the duration of their cancer treatment. Therefore, a great deal of accumulated safety data exists on their use alongside standard of care cancer therapies, spanning chemotherapy, hormone therapy, targeted therapy, and immunotherapy.

Numerous studies have also shown statins can help to improve the effectiveness of conventional cancer therapies such as chemotherapy and radiotherapy and may help reduce the development of resistance to standard treatments.

In addition, there is now emerging data on the potential for statins to exert protective effects on the heart in patients undergoing chemotherapy.

Due to the high numbers of cancer patients taking a statin for other health conditions, it has been possible to conduct large retrospective studies to explore their impact on cancer incidence and outcomes across different cancer types. These studies have been encouraging and therefore acted as a catalyst for further research, including a growing number of human trials.

Lipophilic statins

The overall data is particularly compelling on the beneficial effects of fat-soluble lipophilic statins in cancer, rather than water-soluble hydrophilic statins.  In addition, lipophilic statins cross the blood-brain barrier more readily.  Atorvastatin, simvastatin and pitavastatin are lipophilic statins, whereas rosuvastatin, pravastatin and fluvastatin are more hydrophilic. As a lipophilic statin, atorvastatin has been extensively explored in the context of cancer and has been generally shown to have superior anticancer effects at the cellular level compared to other less fat-soluble statins. It also has the most extensive safety database due its widespread use for its labelled indication, and allows for dose escalation (as tolerated) to the highest dose achievable.

The power of statins in combination with other medicines

Recent research has demonstrated the potential for enhanced benefit from statins alongside other off-label medicines. e.g. statin + metformin in prostate cancer and endometrial cancer, and statin + metformin + NSAID in lung cancer.

Such studies support the scientific approach at the core of Care Oncology, namely that multiple points of intervention are likely to be needed for a metabolically targeted therapy to have the potential to be truly effective. This is the reason we devised a coherent combination of medicines to address related mechanisms involved in cancer cell metabolism. In this way, the activity of each drug, when given in combination, can potentially produce a synergistic effect and agents do not interfere with or impede one another.

COC Protocol Medications – Mechanisms of action

Diagram of cell breaking down each part's capabilities

A word on contradictory/inconclusive studies

We chose the combination for the COC Protocol carefully – because of the wealth of data in cancer and the safety profile of the medicines separately, together and with standard of care therapies.

This level of safety and efficacy data does not exist for most other off-label medicines, particularly in a combination setting.

We believe it is important to assist our patients to assess different types of evidence and the likely significance of reported results. Fundamentally, our position is that limited pre-clinical data in isolation should be approached with caution – the pharma industry writes off billions of dollars annually in the quest to translate lab studies in rodents to relevant findings for safe and effective treatment of humans.

Recently, several patients have asked us to comment on this paper: Statins have biphasic effects on angiogenesis (Weis et al 2002)

In response to this, we would make the following points:

  • Since 2002 there has been a wealth of supportive published papers on the potential of statins in numerous cancers, especially as regards lipophilic statins (e.g. Atorvastatin) and including human clinical trials.
  • The study referenced is 18 years’ old and laboratory based, in mice. To use mouse body weight as a direct extrapolation to humans is simplistic and inaccurate and human dosing is never based on preclinical research. Without corroborating human data, it is not possible to draw firm conclusions on the possible effects of statins on angiogenesis or any other potential mechanisms relevant in an anticancer setting.

Doses of all medications in humans must be titrated to the individual to avoid toxicities. In the case of Atorvastatin, 40mg once a day is considered a potent therapeutic dose.

  • A common feature of contradictory or inconclusive studies is that frequently they do not research the drug in question alongside standard of care therapies and/or they consider it as a single agent rather than deployed as one component of a coherent metabolically targeted combination.
  • Some cancer research on single agent statin does suggest a greater potential for overall anticancer therapeutic benefit at higher doses, which is why we seek to establish patients at 40mg Atorvastatin daily wherever safe to do so, rather than prescribing a lower dose. Use of Atorvastatin also allows for the possibility of escalating further to 80g daily depending on tolerance, satisfactory lab values and consideration of standard of care therapies and other concomitant medication.

Where it is not a suitable for a patient to be on a 40mg daily dose, our clinicians may still consider a lower dose to be worthwhile, again keeping in mind the principle that the potential for therapeutic benefit is amplified by the combination of medicines.

  • It is key to remember that all the COC Protocol medicines have multi-faceted effects in cancer and that we are using them in combination with standard of care therapy and with each other. Both Mebendazole and Metformin also demonstrate the potential to inhibit angiogenesis.

Further information

Visit our website to read more about statins and the other COC Protocol medications in the context of specific cancer types – https://careoncology.com/ – Click on “COC – Select Cancer Types” from the homepage menu

Click here to read our research paper published in Frontiers which provides more detail on our approach and includes preliminary results for our Glioblastoma IV brain tumor cohort. https://www.frontiersin.org/articles/10.3389/fphar.2019.00681/full

How could the COC Protocol help you? – Metastatic Breast Cancer

This month’s newsletter features a documentary charting the journey of one of our patients with metastatic breast cancer.

Early in 2018, Yvonne was diagnosed with stage IV breast cancer with multiple metastases in her liver. Faced with a bleak prognosis, she began to research what else she might be able to do in addition to her standard treatment to increase the odds of a positive outcome.

She found Care Oncology and was able enroll on our adjunctive metabolic treatment program designed to complement her conventional care. She also made changes to diet and nutrition and other aspects of her lifestyle.

Yvonne’s daughter Georgia works as a TV researcher and broadcast journalist in London, UK and in 2019 they made a documentary film about Yvonne’s journey. Here’s what Georgia has to say about her mother and the film they made together:

“By using cheap, existing drugs in combination with the conventional cancer treatments, alongside changes to diet and nutrition, we believe mum is living a healthier life with cancer than she was before her diagnosis. This documentary investigates all aspects of “starving cancer” and speaks to those who swear by it, as well as those who totally refute it.”

November 2020 – Zoom update with Yvonne & Georgia

Yvonne and Georgia caught up with Yvonne’s Care Oncology physician, Dr Ndaba Mazibuko, just before Thanksgiving. They were joined by Dr Chuck Meakin, US Medical Director. It was truly inspiring for our doctors to hear that Yvonne continues to do very well clinically with ongoing stable disease, no new tumors in the liver and no sign of any suspicious lesions in other organs.

She also describes how the research and pursuit of additional evidence-led interventions, like the COC Protocol, has given her a mental and emotional boost, allowing her to exert positive influence over circumstances which, all too easily, can feel as though they’re outside a patient’s control.

At Care Oncology, we seek to empower our patients to help them live longer and better lives. But, we’re also with them every step of the way, providing ongoing medical supervision, regular follow up appointments with our doctors and access to nurse support. 

I am 29 and I have lung cancer – No, I do not smoke

I am 29 and I have lung cancer. And, before you ask: No, I do not smoke, have never smoked, and most certainly will NEVER start smoking so long as these sturdy lungs of mine can breathe. Cigarettes, as well as any of their close cousins [e.g. vape pens, e-cigarettes, cigars, or pretty much any object stuffed with injurious chemicals intended for bodily consumption], I have always found worth strenuously avoiding like the plague, or that irritable uncle of yours who corners you at family gatherings only to lecture you on society’s innumerable shortcomings, or the regrettable state of our politics, or the lackluster quality of today’s music, or…well, you get the point. You’ll have to forgive the acerbity, dear reader, as the general public – perhaps, even you – have succumbed to a dreadful misconception about me and others suffering from this horrible affliction. Remember this: You need not have smoked to get lung cancer, and that is a truth even the mighty gods of Olympus cannot impugn. Exposure to radon gas, air pollution, second-hand smoke, and, if recent research is to be believed, even third-hand smoke, are just some of the ways you can get lung cancer. More infuriating still, smoking is the leading preventable cause of most cancers[1] in the United States; however, when some unfortunate sap gets hit with a bladder cancer diagnosis, this is usually met with unhurried expressions of sympathy rather than, as is the case with lung cancer patients, an on-the-spot examination of the troubled victim’s [ugh, do I hate that word!] “history” of smoking.

You may be surprised by this. Appalled, even. Don’t be. It’s happened more times than I care to recount. Now, you’re probably wondering how someone like me – a healthy, physically active [I’m an avid runner], 29-year-old never-smoker – got lung cancer, right? Beats me. What you may not know is that in most patients with a similar profile [young, healthy, never-smoker], lung cancer is often discovered at a more advanced stage, when treatment options are few-and-far between compared to when the disease is caught at an earlier stage. In my case, I was completely asymptomatic. I had no difficulty breathing, my organs were functioning as they should, and I felt no discomfort whatsoever. My primary care physician even once joked during a follow-up appointment to discuss the results of my annual physical that I was “medically boring.” [Well, doc, you should see me now!] Until, of course, that fateful day in June of last year when I felt the left side of my body seize up while walking back to my office at work. I was later to discover that the cause of this seizure was an acorn-sized tumor that had metastasized to my brain from the primary tumor site in my right lung. You could imagine my surprise when I was given my diagnosis. Time immediately stood still in that moment. Like raging river waters that had broken through a dam, thoughts came flooding in: How did this happen? Where do I go from here? Could I have done anything to prevent this? And, most disturbingly of all, did I do anything to DESERVE this?

Prevention. We know the most effective way to treat patients is to not have to treat them at all. Despite some of my friends’ and family’s’ smoking habits, I never took up smoking and knew I never would. I ate right, barring the occasional late-night excursion to Taco Bell, exercised regularly (I still do), and did all I could to maintain my “medically boring” reputation. Sadly, it appears, that making all the right moves in life does not always guarantee you’ll come out on top. Luck, sometimes, plays an even greater role in the affairs of our species more than we care to admit. Let my story serve as a prickly and uncomfortable reminder of that fact.

You may be further tempted to ask: Could I have done anything to catch this disease at an earlier, more manageable stage? If only. What’s unfortunate is that, given my medical profile, the tests presently available to screen for lung cancer in patients for preventative or early treatment purposes would not have been available to me. Why? Well, among the eligibility criteria governing which patients are considered “high-risk” and should have annual low-dose CT screenings, the American Cancer Society lists the following: (1) persons  “aged 55 to 74 years and in fairly good health,” (2) persons who “currently smoke or have quit within the past 15 years,” and (3) persons who “have at least a 30-pack-year smoking history.”[2] Strike 1. Strike 2. Strike 3. I’M OUT! What about an X-ray, you ask? Not quite as effective as a CT scan. Not to mention, when I was hospitalized in June of last year, an X-ray of my chest was done, and this revealed absolutely nothing; the tumor was not quite large or dense enough for it to be picked up by the machine. And, though liquid blood biopsies are a novel and promising new screening mechanism employed by oncologists today to detect early signs of cancer, I would still have not been eligible to receive such testing for the same reasons that excluded me from receiving a low-dose CT screening; namely, I wasn’t considered “high-risk.” And that, to use the language of my gambling cohorts, is what we would call, a wash. Or, as my Francophilic friends would hurry to proclaim, C’est la vie.

However, I do not want to give you the wrong impression, dear reader. I’m not writing you in order to elicit your sympathy or pity. The world has no shortage of stories like mine, and I count myself not as possessing any special status far and above theirs. Though engendering a world in which love, kindness, and mutual understanding become ever more ubiquitous is a noble goal worth pursuing, my more immediate aim is simply to bridge what I and countless others see as a glaring gap in our public consciousness about lung cancer – its causes, its prevalence, and its victims. I bet you didn’t know that lung cancer is the LEADING cancer-killer in the United States, did you? Also, I can guess with near-to-absolute certainty that you didn’t know lung cancer kills MORE WOMEN every year than breast, uterine and ovarian cancer COMBINED. In fact, it is fairly evident lung cancer has no sex-specific predilections when it comes to choosing its victims, killing more men and women than any other cancer in the United States. I suppose, then, that in light of these findings, you’d be surprised (aghast, perhaps) to hear that lung cancer research garners the FEWEST dollars every year than any other cancer research initiative does? I can just picture you now, sitting there with furrowed brow, ponderously searching for an explanation that would account for such a depressingly large funding disparity. It’s quite simple, really: Lung cancer patients are seen as “deserving” their fate because they knew the risks when they began smoking. Of course, you need not be a master logician to see just how patently absurd this belief is. However, since I absolutely relish tearing apart fallacious arguments (my B.A. is in philosophy, after all), I would humbly ask that you allow me this one indulgence.

First, as was already made clear at the beginning, you need not have smoked to get lung cancer. In fact, as the rate of smoking continues to decline, a greater proportion of newly diagnosed lung cancer patients are younger, healthy, never-smokers like me. To edify you further: 60-65% of all newly diagnosed lung cancer cases are amongst people who have never smoked or who quit smoking some time ago. Estimated 10-15% of newly diagnosed lung cancer cases are amongst never-smokers. Sadly, however, the smoking stigma persists, and it is this stigma that needs quashing – and fast.

Secondly, let us dispense with the morally confused and abhorrent belief that anyone “deserves” cancer. Cancer patients are human beings, many of them with families and friends whom they hold dear, and who harbor dreams, goals, and aspirations much like your own. On all accounts, they are neither less nor more human than you are. It smacks as the height of arrogance to believe that any one mortal can sit in judgment of another, consigning them to a fate not of their own willful choosing. And, yes, while those who chose to smoke knew the risks they were assuming, it is also crucial to try to understand the prevailing contextual factors that would explain why such a deleterious habit was adopted to begin with. Passing judgment against those whose lives we may not fully understand makes us into moral monsters, not paragons of virtue. Furthermore, can any morally serious person believe that a mistake, once made, forever forecloses any opportunity for personal redemption? Indeed, is it not this opportunity for redemption that is the sine qua non of the virtue of forgiveness? By the way, you need not be of the religious variety to believe in the power of forgiveness. I, myself, am not particularly religious, though I do harbor spiritual beliefs of my own over which no religious organization or tradition can claim an exclusive monopoly. In short, if we cannot presume to know in their entirety the circumstances that would explain people’s poor past decision-making, it would be just as presumptuous of us to think that we can divine a person’s future chances at redemption or self-transformation. To think otherwise surely taxes the credulity of the credulous, and any person who feigns such omniscience should be treated with the scorn and ridicule that such claims rightfully deserve.

With that said, I suppose you have fully anticipated the crucially important point at which I’ve been driving with these (hopefully) thought-provoking moral queries and observations. If not, permit me to spell it out for you in language both unambiguous and emphatic: If we cannot justifiably rob one of our fellow mortal brethren of the chance to right past wrongs, to seek forgiveness (and, by extension, redemption), or to simply improve upon who they were in the hopes of achieving the best version of themselves, which is indisputably the object of all of our life’s exertions, then why should we allow cancer to do so? Let us not be so quick to heed the Siren call of fatalism, tempting though it be. The fatalistic attitude, which dismisses as un-malleable the circumstances of human existence, is something we must forcefully repudiate, and not just because it traffics in fabrications, but because it is crippling to the human spirit – a spirit that has made possible so many brilliant, innovative, and important achievements our species can lay claim to. If our species is ever to claim victory against such a historically cunning and formidable foe as cancer, than we must not let this spirit wane. To do otherwise would be to admit defeat, and defeat is most certainly not an option.

Ok, enough moralizing, lest I dissuade you from engaging in that introspection, which, I hope, my own ruminations put to paper on the topic of my own diagnosis provoke in you. If I have failed in that – if I have not sufficiently convinced you of the undeniable importance of self-reflection and the critical need to challenge unremittingly your underlying preconceptions, presuppositions, and prejudices – than, I’m afraid, people like me will continue to suffer needlessly under an unforgiving and confused stigma. Nevertheless, I have hope that, as Abraham Lincoln put it so poetically during his legendary address to those assembled at Gettysburg in 1863, that the “better angels of our nature” will prevail in the end.   

In truth, I take immense comfort in knowing that it is the untrammeled innovativeness of our species, together with our ability to remain hopeful during the darkest and bleakest of times, that will lead us with meteoric propulsion towards a cure for cancer of all types. Indeed, I do not think it exaggerated to claim that there has never been a better time to have cancer – heaven forbid you should get it. And this is not simply because of the promising new developments in conventional treatment options that we hear touted by the medical industry. No. We are at the beginning of a new epoch in the way cancer is understood; specifically, with respect to what causes it, and, thus, how it can be more effectually prevented and treated. Thanks to the unflagging efforts of pioneering medical professionals like Dr. Thomas Siegfried and Dr. Jason Fung (just to name two working professionals on a very long roster of professionals) and fastidious investigative journalists like Travis Christofferson, we have come to understand that our previous conceptualization of cancer as a genetic – or exclusively genetic – disease is woefully, indeed, fatally misguided.

In fact, as Dr. Siegfried and others have argued, cancer is a disease caused by a disruption in the normal metabolic functioning of our cells, and the genetic mutations conventional practitioners make haste in detecting are simply the effects (not the cause of) such metabolic dysfunction. New evidence continues to be amassed in support of this hypothesis, while pre-existing evidence thought to support the conventionally embraced genetic causal theory of cancer has been shown to be more supportive of the metabolic causal theory of cancer. As Dr. Siegfried and others have pointed out, when hundreds, if not thousands, of several different mutations can occur in even one solid tumor, focusing all our efforts on developing tailor-made therapies that may be able to target one of those mutations, and for a limited period of time, is to make poor use of what few resources and limited time we have in combatting this nefariously wily enemy we call cancer. If the metabolic theory of cancer has any credence – and I believe that it does – than a re-calibration of how we spend our precious time and resources when it comes to fighting cancer is in order.

For example, it may strike you as a surprise to discover that there is evidence to suggest that several re-purposed medications, such as the anti-diabetic drug Metformin, have anti-carcinogenic properties. These repurposed drugs are extremely mild in their toxicity, and are far cheaper to obtain than several conventional chemotherapeutic drugs (but don’t tell BigPharma I said that). It is pathbreaking discoveries, or, in some cases, re-discoveries like these that have been made by organizations, such as my virtual oncology platform CareOncology.com, that are providing cancer patients with a newfound sense of hope where none may have previously existed. Additionally, other unconventional, but no less effective, therapies, such as high-dose IV vitamin C, have been shown to yield great promise as either monotherapies or adjunctive therapies[3].

Furthermore, simple changes to our dietary and eating habits – from the elimination of processed foods and sugar, to increasing our consumption of healthy alternatives, together with time-restricted eating or intermittent fasting and regular exercise – can all serve as effective weapons that you can store in your cancer-fighting arsenal. Uncovering all these latest developments in cancer research, I can honestly say, can be attributed to my voracious appetite for new information and unchecked intellectual curiosity – or, more simply put, to my inability, as my mother would say, to “sit still.” Those have always been two of my greatest assets, but they are assets, I believe, every cancer patient will need should they want to defeat this most cunning and devious of foes.

In some form or another, I have adopted the therapies, prescriptions, and practices mentioned above in my own life, as well as several more the details of which I will spare you (for now). However, I believe I would be remiss if I did not impress upon you the incalculable importance of supporting and maintaining a happy mental life, whether you have cancer or are seeking to keep it at bay (especially, if you’re trying to keep it away). Indeed, I believe that my failure to grasp this fundamental importance contributed, in one way or another, to my getting cancer.  As the influential philosopher Sam Harris once remarked, our minds are all we have, and that is undoutedly true. Though our understanding of the nature of consciousness leaves much to be desired, it is clear on virtually every account that our physical life is largely an extension of our mental life. More precisely put, our physical life is conditioned by our mental life, as the famed epigeneticist Bruce Lipton reminds us in his wonderful book entitled “The Biology of Belief: Unleashing the Power of Consciousness, Matter, and Miracles.”

To bring the point squarely into focus: A happy life suggests a mind that is unburdened of needless complications, indecision, stress, anxiety, and confusion, and can think about and comprehend things lucidly. Unfortunately, much about our contemporary lifestyles makes it all but impossible to cultivate a happy mental life. Social media sites vie for our uninterrupted attention, even as they contribute to the shortening of our individual and collective attention spans. Cable news networks shower us incessantly with one “news alert” after another, with each new alert more terribly inconsequential than the one that preceded it. And advertisers bombard us relentlessly with suggestions that we should all purchase the latest cellphone, luxury vehicle, or what-have-you in order to fill the void we feel deep inside us – a void, ironically enough, that is of the advertising industry’s very own self-serving creation. The stress induced by trying to “keep up with it all” is, I firmly believe, what is partly driving cancer to overtake heart disease as the leading cause of death on the planet. 

That is why I’ve decided to cut myself loose from these harmful distractions, and it’s why I think you should do so as well. Instead of feverishly checking your Twitter feed for the latest musings of a famous know-nothing, crack open a book on a subject you find interesting. I’m currently reading a brilliant biography on one of my favorite philosophers, David Hume. Unlike mindlessly scrolling through my social media feed, with the turn of each page, my mind does not suffer from diminishing returns. Rather than watching your politically-preferred cable news network of-choice, turn off that television and use that time to find a quiet place to meditate – to placate your mind, not to agitate it further with gratuitous noise, contrived conflict, and vacuous commentary. Lastly, find it in yourself to learn to love yourself. Without question, I’ve been characterized as somewhat of a perfectionist by those who know me best; however, in my drive to be the best, I was often my harshest critic. It was soon after I received my cancer diagnosis that I realized this was a terrible mistake. The biggest cause of the stress in my life came not from the outside, but from within.  I regret not realizing that earlier on. So, try not to be so hard on yourself. Perfection at the expense of finding that internal peace that makes for a happy life is too high a price to pay. So, refrain from paying it.

In conclusion, I would like to thank you for taking the time out of your busy (but, hopefully, not too busy) day to read my story. I hope it has aroused your curiosity and given you pause to reflect on some of those pre-conceived notions about cancer – especially, lung cancer – that you may have harbored prior to reading this article. Furthermore, I hope you use my story – improbable, though it may sound – to counter what are the altogether pernicious and prevalent misconceptions about lung cancer patients discussed earlier. Remember, if you have lungs, you can get lung cancer; it’s as simple as that, so consider a prevention strategy noted above. Now, before I dispatch with another one of my moralizing tirades and risk losing the progress I’ve made up until now, I’ll end it here. Go forth, and remember, that your personal well-being is the only thing of any real consequence in this life. And, in case you are wondering, I am thriving 18 months since that difficult day in June, and, for now, all is in remission. Rest assured; I intend to keep things that way.

With Love,

Thomas

[1] “Cancers Linked to Tobacco Use Make up 40% of All Cancers Diagnosed in the United States.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 10 Nov. 2016, www.cdc.gov/media/releases/2016/p1110-vital-signs-cancer-tobacco.html.

[2] “Lung Cancer Screening Guidelines.” American Cancer Society, www.cancer.org/health-care-professionals/american-cancer-society-prevention-early-detection-guidelines/lung-cancer-screening-guidelines.html.

[3] “A Combo of Fasting plus Vitamin C Is Effective for Hard-to-Treat Cancers, Study Shows.” ScienceDaily, ScienceDaily, 12 May 2020, www.sciencedaily.com/releases/2020/05/200512151941.htm.

Future of Medicine Book “Curable” – EP09: Travis Christofferson (Author)

In this ninth episode, Travis Christofferson provides an overview of his new future of medicine book “Curable: How an Unlikely Group of Radical Innovators is Trying to Transform our Health Care System”. He covers the great inefficiencies of healthcare and harm it’s doing to swaths of the patient population. He explains it’s too qualitative than quantitative, that incentives are misaligned. He offers hope by urging a shift to being data-driven.

 

COC Comment: New Research on COC Medications and NSAIDs

A large South Korean registry study has shown that the combination of two COC Protocol medications (metformin & statin) alongside aspirin reduced lung cancer incidence and mortality. The study also indicated that the potential for benefit increased the longer the duration of use –

Summary here
Full paper here

This is interesting as:

a) it adds to the research literature which suggests the combination of metformin and statin may exert synergistic anticancer effects (see, for example, recent papers in the context of Prostate and Endometrial cancer. Click to read more

b) it bolsters existing evidence on the potential usefulness of NSAIDs such as aspirin and ibuprofen in a cancer context. Click to read more

COC Comment: Research on New Doxycycline Derivative

Frontiers | A Myristoyl Amide Derivative of Doxycycline Potently Targets Cancer Stem Cells (CSCs) and Prevents Spontaneous Metastasis, Without Retaining Antibiotic Activity | Oncology

Read the article Here

“This is very exciting and important research, which we believe holds real promise.

However, as with the development of any new chemical entity, further work must first be completed, including human pharmacokinetics, and toxicology, before a new drug could reach the market. We would like to wish Prof Lisanti and his team all the very best taking this project forward.
In the meantime, patients continue to seek out treatments which could benefit them today.

As highlighted by this paper, existing, licensed Doxycycline is a known cancer stem cell inhibitor and potentially potent antimetastatic agent in its own right, particularly when administered as one component of a comprehensive adjunctive combination (the COC Protocol) aimed at disrupting and weakening the overall metabolic machinery of abnormal cells.

Doxycycline is a bacteriostatic rather than bactericidal antibiotic, meaning it stops bacteria from reproducing while not necessarily killing them. It is generally believed to be less disruptive to gut bacteria than other classes of antibiotics and studies show it is almost completely absorbed in the upper gastrointestinal tract.

Furthermore, it is safely taken over the long-term as prophylaxis in chronic lung conditions such as COPD and also in malaria. At Care Oncology we seek to further limit overt antibacterial effects by pulsing cycles of Doxycycline at intervals rather than administering it continuously.

” Active” Active Surveillance in Prostate Cancer

Dr. Charles Meakin
Dr. Charles Meakin

As Chief Medical Officer of Care Oncology, I have witnessed many prostate cancer patients (in the above scenarios) find their way to our metabolic protocol to engage a truly “Active” Active Surveillance strategy.

One of the therapeutic options upon diagnosis of prostate cancer is the prospect of deferring commencement of traditional therapies while one monitors the PSA level. (https://www.nccn.org/patients/guidelines/content/PDF/prostate-patient.pdf).

In line with this, at Care Oncology we have many men who have chosen to start the COC Protocol and ultimately been able to enjoy long periods away from traditional therapy and its side effects and cost. It is possible the protocol is having a favorable impact on proliferation drivers that foster the cancer cell growth reflected in a rising PSA, and we are tracking our cohort over time to analyze this further.

The strategy may be a sensible one since many patients are diagnosed with indolent cancers and at an age where they are likely to have comorbidities. Hence the statement that many men with prostate cancer “die with it, but not from it.”  The first step is identifying the risk category of the prostate cancer (PSA level, Gleason Score, degree of spread etc) versus the anticipated life expectancy of the patient. Once these two characteristics have been evaluated, one can consider which threat is the greatest – the prostate cancer versus the other advancing potential causes of death as men age. The traditional Active Surveillance strategy incorporates frequent PSA  or tumor marker checks as measured in an annual biopsy procedure, which can become very challenging for patients (https://pubmed.ncbi.nlm.nih.gov/28512731/). Generally, about 50% of the patients will transition to some treatment over a ten-year period without any loss of treatment success as compared to immediate treatment with surgery or radiation.

The difficulty with active surveillance is going to bed every night, knowing there may be cancer growing in your body. Some men handle this dilemma better than others, and I have noticed that after one to two years, many say, “Hey Doc, can we go ahead and treat it!”.

In my big cancer center oncology role, during this watchful waiting window, I would frequently put patients on some nutrition and supplements strategies associated with anti-proliferation. In many instances, I would see the PSA reduce or even flatline, resulting in emotional satisfaction for the patients, many of whom reported feeling able to exert some element of direct control over their disease for the first time. Personally, I found management of these patients very rewarding too, as I believe there is a strong likelihood the “active” strategies we deployed also had a positive impact on other existing chronic health conditions  or chronic disease risk factors prevalent in men of a certain age.

The other situation that frequently would come up with similar options and implications is the very common occurrence of PSA failure after attempted curative surgery or radiation (External Beam or Implant). At this unfortunate juncture, men often continue to feel fine. Still, they are tortured by the knowledge that the cancer is growing back and may be a problem at some time in the future, and some new therapies may be necessary despite the initial treatment. This dilemma can be complicated by consideration of therapies such as androgen blockade that can accelerate other chronic comorbidities and impact the quality of life in order to treat an asymptomatic lab value like the rising PSA.

We’re very excited about the encouraging preliminary results we are seeing, so in addition to continuing to audit the outcomes of our own patients at Care Oncology, we have now also begun  approaching large urology  groups to explore initiating the COC metabolic protocol as a  formal study, given the ease of implementation, fundamental affordability of the program and most importantly how empowering it has the potential to be for patients.

Stay strong and curious,

Charles Meakin MD

 

The tumor microenvironment, immune response and the COC Protocol

The body’s own anti-tumor immune response can be a powerful weapon against cancer. Once mobilized it can target and destroy cancer cells very efficiently. New and developing immunotherapies seek to harness this ability. But tumors are also very good at recruiting the immune system for their own protection. Scientists are looking for ways to help improve the body’s immune system respond to cancer and help facilitate immunotherapy treatment activity.

Tumor Associated Macrophages (TAMs) are key immune cells which help to modulate the body’s own anti-tumor immune response. TAMs circulate in the region immediately around the tumor, called the tumor microenvironment. Once recruited by the tumor, TAMs can help to promote growth and spread of tumor cells. They can also help to stimulate the formation of new blood vessels (angiogenesis) to feed the tumor.

TAMs are generally thought to ‘polarize’ into anti-tumor M1-type or pro-tumor M2-type cells, depending on outside signals they receive. This is a growing field of research, and scientists are still working to understand just how and when TAMs can polarize to promote or inhibit cancer growth. However, there is emerging evidence that polarization of TAMs may in part be influenced by the metabolic state (i.e. nutrient availability) of the tumor microenvironment. In this way, TAMs and cancer cells may also be able to directly influence each other, depending on their own metabolic activity (Vitale et al, 2019).

In line with this, emerging evidence also suggests that the COC Protocol medications (which can help to influence cell metabolic activity), may help to beneficially modulate the anti-tumor activity of TAMs and other immune cells.

For example, a 2018 lab study found that metformin can ‘skew’ TAM polarization in the tumor microenvironment from pro-tumor M2 to anti-tumor M1. Metformin inhibited both tumor growth and angiogenesis in this study (Wang et al. 2018). Other studies suggest metformin may also boost other immune cell functions, potentially helping to increase abundance of (anti-cancer) tumor infiltrating lymphocytes, and enhancing the cancer cell-killing ability of  T-cells (Pereira et al 2018).

Mebendazole has also been shown to help initiate the TAM mediated anti-tumor immune response. In one study, gene expression profiling in mebendazole-treated breast cancer and leukemia cells showed that mebendazole strongly upregulated several genes related to activation of the anti-tumor M1 monocyte/macrophage (i.e. TAMs). A further lab study in colon cancer cells also showed that mebendazole’s tumor suppressive effect is intrinsically linked to monocyte/macrophage immune cell response (both studies reviewed in Guerini et al 2019).

Further reports suggest that statins and doxycycline can also have antitumor effects on TAM polarization and other immune cell functions. For example, in a study which analyzed samples from patients with lung cancer, statin use was associated with reduced levels of pro-tumor TAMs, and reduced tumor invasiveness (Dujaily et al. 2020). And in a mouse model of breast cancer, statin helped to improve anti-tumor T cell infiltration into tumors, and decrease the number of M2-type TAMs. Initiation of new cancerous lesions in these mice was also decreased (Mira et al. 2013). In a different study using a mouse model of breast cancer, doxycycline slowed tumor growth, and this effect was associated with changes in levels of cytokines and TAMs (Tang et al. 2017).

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Important Notice

Purpose of this article

This article is an overview of some of the scientific and medical published literature concerning the medications which comprise the patented Care Oncology protocol. Care has been taken to select relevant articles supporting the off-label use of these medicines in a clinical setting for the adjunct treatment of cancer. This article does not purport to be a comprehensive review of all the evidence, nor does it capture all the potential side-effects of such treatment.

This article is for information purposes only and it does NOT constitute medical advice. The medicines discussed herein are available on prescription-only and should not be taken without consultation with your doctor or other professional healthcare provider. Care Oncology doctors will discuss the suitability of these medicines with you and will liaise with your doctor or oncologist to discuss their suitability for you.

You must NOT rely on the information in this article as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about any medical matter you should consult your doctor or other professional healthcare provider. If you think you may be suffering from any medical condition you should seek immediate medical attention. You should never delay seeking medical advice, disregard medical advice, or discontinue medical treatment because of information contained in this article.

Copyright

The copyright in this article is owned by Health Clinics USA Corp and its licensors.

Patent

The Care Oncology (“COC”) Protocol is protected by United States patent US9622982B2 and by various additional international patents.

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References

Dujaily, Esraa Al, Juvenal Baena, Madhumita Das, Marco Sereno, Claire Smith, Tamihiro Kamata, Leah Officer, Catrin Pritchard, and John Le Quesne. 2020. “Reduced Pro-Tumourigenic Tumour-Associated Macrophages with Statin Use in Premalignant Human Lung Adenocarcinoma.” JNCI Cancer Spectrum. https://doi.org/10.1093/jncics/pkz101.

Guerini, Andrea Emanuele, Luca Triggiani, Marta Maddalo, Marco Lorenzo Bonù, Francesco Frassine, Anna Baiguini, Alessandro Alghisi, et al. 2019. “Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature.” Cancers 11 (9). https://doi.org/10.3390/cancers11091284.

Jeong, Hoibin, Sehui Kim, Beom-Ju Hong, Chan-Ju Lee, Young-Eun Kim, Seoyeon Bok, Jung-Min Oh, et al. 2019. “Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis.” Cancer Research 79 (4): 795–806. https://doi.org/10.1158/0008-5472.CAN-18-2545.

Mira, Emilia, Lorena Carmona-Rodríguez, Manuel Tardáguila, Iñigo Azcoitia, Alicia González-Martín, Luis Almonacid, Josefina Casas, Gemma Fabriás, and Santos Mañes. 2013. “A Lovastatin-Elicited Genetic Program Inhibits M2 Macrophage Polarization and Enhances T Cell Infiltration into Spontaneous Mouse Mammary Tumors.” Oncotarget 4 (12): 2288–2301.

Pereira, Melo, Low, de Castro, Braga, Almeida, Batista de Lima, Hiyane, Correa-Costa, Andrade-Oliveira, Origassa, Pereira, Kaech, Rodrigues, Olsen, Camara, 2018.  Metformin exerts antitumor activity via induction of multiple death pathways in tumor cells and activation of a protective immune response.” https://doi.org/10.18632/oncotarget.25380

Tang, Xiaoyun, Xianyan Wang, Yuan Y. Zhao, Jonathan M. Curtis, and David N. Brindley. 2017. “Doxycycline Attenuates Breast Cancer Related Inflammation by Decreasing Plasma Lysophosphatidate Concentrations and Inhibiting NF-ΚB Activation.” Molecular Cancer 16 (February). https://doi.org/10.1186/s12943-017-0607-x.

Vitale, Ilio, Manic, Gwenola, Coussens, Lisa M, Kroemer, Guido, Galluzzi, Lorenzo. “Macrophages and Metabolism in the Tumor Microenvironment.” Cell Metab. 2019;30(1):36-50. https://doi:10.1016/j.cmet.2019.06.001.

Repurposed medicines and COVID-19

The coronavirus pandemic has put drug repurposing in the spotlight in a way that has never happened before. If shown to be effective in COVID-19, existing medicines with known safety profiles can be brought to clinical use quickly and will likely offer a more rapid hope of tackling the virus than a vaccine. In nearly all cases, use of existing drugs will also offer a highly affordable solution.

Many Artificial Intelligence and bioinformatics studies are cross-referencing vast numbers of different medicines with new information about the biology of SARS CoV-2 (the virus which causes COVID-19) and dynamic clinical trials are taking place all over the world. These trials have secured regulatory approval far more quickly than would normally be the case and many have been designed to allow for rapid review of information so that the most promising agents can be prioritised.

More research is required before various medicines can be widely prescribed as COVID-19 prophylaxis or treatment, but the direction of travel is encouraging.

As this data develops, it is interesting to note that various druggable targets associated with the COC Protocol medications in cancer (e.g. glycolysis, lipid accumulation, inhibition of pro-inflammatory cytokines) also appear to be relevant in COVID-19.

Please see below for further reading.

The SARS-CoV-2 Transcriptional Metabolic Signature in Lung Epithelium

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3650499

 

Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis

https://www.ajtmh.org/content/journals/10.4269/ajtmh.20-0375

 

Metformin in COVID-19: A possible role beyond diabetes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190487/

 

Modulation of Cytokine and Cytokine Receptor/Antagonist by Treatment with Doxycycline and Tetracycline in Patients with Dengue Fever

https://www.hindawi.com/journals/jir/2011/370872/

 

Further aspects of doxycycline therapy in COVID‐19

https://onlinelibrary.wiley.com/doi/full/10.1111/dth.13810

 

A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulates the Innate Immune Response in COVID-19 Patients

https://chemrxiv.org/articles/preprint/A_Combination_of_Ivermectin_and_Doxycycline_Possibly_Blocks_the_Viral_Entry_and_Modulate_the_Innate_Immune_Response_in_COVID-19_Patients/12630539

 

In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30316-8