DCA Papers and Clinical Trials

DCA papers and clinical trials

For almost a decade there has been a growing interest in Dichloroacetate potential to successfully get rid of cancer while causing minimal harm to healthy organs. DCA is a relatively cheap substance which cannot be patented by the pharmaceutical industry, thus it could not generate profit for private drug companies. Right now, because of this reason, Dichloroacetate isn’t receiving enough funding and attention which it deserves.

Despite that, there are plenty of ongoing and completed studies which examine the facts of DCA appliance for therapy. This site will present a handful of completed scientific investigations and will constantly update you with the most recent publications related to the subject.

Below you can find full research reports of Sodium Dichloroacetate (DCA) as an anti-cancer agent.

DCA History

DCA history

Since 1973 Sodium Dichloroacetate (DCA) was used to treat various mitochondrial disorders. It inhibits the activity of pyruvate dehydrogenase kinase, and reduces the accumulation of lactate in body tissues. Its usage for treating lactic acidosis has been successful and is still continued to this day, it is used in several research and medical centers in the United States and Canada.

The majority of the people who have used DCA are children with congenital mitochondrial disorders. The use of the drug could resume the normal function of the cellular enzymes and prevent further neurological damage, mental disability, microcephaly, blindness and movement disorders. Dichloroacetate safety has been confirmed long before the idea, that it could be helpful for someone who has cancer.
In 1920s German biochemist Otto Warburg found abnormalities in metabolism in cancer cells. Normal cells obtain energy by glucose oxidation, which requires the presence of oxygen. Cancer cells depend on glycolysis to obtain energy, and it can occur without the presence of oxygen, but is dependent on the availability of sugar. Cancer cells favor glycolysis even in the presence of adequate oxygen for oxidative phosphorylation, leading to a voracious appetite for glucose. This phenomenon prompted Warburg to propose that mitochondrial malfunction was the primary cause of cancer. Sodium Dichloroacetate (DCA) works by inhibiting the
“Warburg Effect”.

DCA forces cancer cell to abandon its preferred metabolic process and also induces apoptosis, or cellular suicide. The reason cancer is so fast growing is that the mitochondria have been deactivated, so the cells evade apoptosis and are able to grow in the absence of oxygen. DCA reverses this. In effect, DCA directly causes cancer cell apoptosis and works synergistically with other cancer therapies.

• In 2007 dr. Evangelos Michelakis of the University of Alberta in Canada published a research paper that renewed interest in DCA. It showed potential of DCA to shrink cancer tumors. In the study DCA was administered to rats with transplanted tumor cells (brain, breast and lung). DCA killed cancer cells without affecting healthy cells. The rats’ tumors decreased by up to 70 percent in three weeks of DCA treatment:
A Mitochondria-K Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth

Other researchers have followed and confirmed anti-cancer effects of DCA. Yet most of the studies have been done on cell cultures in the lab, and not on the cancer patients themselves. But results are very consistent, suggesting DCA is effective against a wide variety of cancer types.

• In 2013, Phase 1 clinical trial of dichloroacetate (DCA) was completed in Canada. It showed that DCA is feasible and well tolerated in patients with recurrent malignant gliomas and other tumors metastatic to the brain using the dose range established for metabolic diseases:
Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors

• In another study, five glioblastoma multiforme patients were treated with oral DCA for up to 15 months. The research showed clinically promising results in four of the five patients:
Metabolic modulation of glioblastoma with dichloroacetate

• Medicor Cancer Center in Canada is a cancer clinic currently offering DCA therapy for it’s patients. It has published several case studies about the safety and effectiveness of DCA. Its real-world Observational DCA patient data is available to the public.

• Till this day, there are several ongoing clinical studies and a lot of pre-clinical research going on. Recently it has been noted that DCA can work by itself, however, it provides the maximum results in combination therapy with other drugs for a prolonged time period.

Methods and Supplements for Preventing DCA Side Effects

Methods and supplements for preventing DCA side effects

When you begin your Sodium dichloroacetate regimen, it is crucial that you take supplementation which provides protective benefits. This way you minimize the chance for developing reversible peripheral neuropathy asas well as other adverse reactions related to the nervous system.

Below you will find a list of supplements which are essential or recommended for a pleasant DCA usage experience with the lowest achievable side effect probability.

▪ Vitamin B1 – thiamine.(Necessary)
(take one and a half 100mg capsules / tablets twice a day. Take it before breakfast and before lunch.
An alternative way – take 100 mg three times a day. Total – 300 mg)

The B group vitamin thiamine appears to have a protective effect against peripheral neuropathy. This food supplement can be used not only for DCA induced neuropathy but also for other neuropathies which are caused by diabetes and chronic alcohol abuse. (Ref.)

We recommend using benfotiamine because it can be absorbed over five times better than the ordinary thiamine form.

In addition, the newest research claims that Vitamin B1 can have an antiproliferative effect on malignant cells. (Ref.)

▪ Alpha–Lipoic acid. (Necessary)
(take one 300 mg R+/S- capsule/tablet three times a day or take one 150 mg R+ capsule/tablet three times a day. Take it before breakfast, before lunch and before dinner. Total – 900 mg (R+/S-) or 450 mg (R+))

α-Lipoic acid is a strong antioxidant, it helps avoiding and controlling symptoms related to neuropathy. The supplement can lower anxiety, memory problems as well as help keeping away from peripheral neuropathy manifestations such as tingling, burning, painful sensations and numbness. (Ref.)

You can use smaller doses if you’re taking R-form α-Lipoic acid.
If you have Racemate α-Lipoic acid (which is a mix of R and L forms), you should take a twice larger dose to fulfill your daily goal.

Don’t take α-Lipoic acid if you’re receiving chemotherapy or radiotherapy.
α-Lipoic acid has a strong antioxidative effect that can interfere with the effectiveness of chemotherapy. For this reason, we recommend staying away from this supplement a couple of days before the chemo, during the treatment and 1 week after the chemotherapy. (Ref.)

α-Lipoic acid also can decrease the effectiveness of radiotherapy. This is why we recommend avoiding taking it for several days before, during and 2 week after these procedures.

▪ Acetyl L-Carnitine. (Recommended)
(take on 600mg capsule / tablet three times a day. Take it before breakfast, before lunch and before dinner. Total – 1800 mg)

The majority of scientific studies claims that Carnitine can be an effective aid to lower peripheral neuropathy. Acetyl L-Carnitine is also an attractive option because its longtime usage does not cause any side effects and carries no health risk. (Ref1.), (Ref2.), (Ref3.)

α-Lipoic acid and Acetyl L-Carnitine both appear to have a synergistic effect at preventing neuropathy.

On rare occasions, Sodium dichloroacetate administration can result in heartburn or nausea. If this is the case, try taking DCA after you eat a little bit of food and drink some fluids to avoid your stomach becoming irritated.

If that did not resolve the problem, you should try taking medications that lower gastric acid secretion – proton pump inhibitors.
Any type of PPI is acceptable provided the fact that they don’t have any major differences.

▪ Pantoprazole. 
(take one 40mg tablet per day, at the same time. Take it at least 30 minutes before your meal and DCA.)

For convenience purposes, we recommend using Pantoprazole because it doesn’t seem to have any poor interactions with other medications.

If you began experiencing moderate side effects or develop a stronger form of peripheral polyneuropathy – stop taking DCA until the adverse reactions become acceptable or disappear completely.

All Sodium dichloroacetate side effects are reversible.

When you stop taking DCA, the majority of the side effects disappear in several days. Peripheral neuropathy can take up to a week or, in rare occasions, a couple of weeks to resolve completely. (Ref.)

Additionally, if you have an opportunity – we recommend regularly performing blood tests and checking the blood serum for tumor marker levels.

UltrasoundComputer tomography scansMagnetic resonance imagingPositron emission tomography are imaging tests that can provide more information about the dynamics of your overall health, and most importantly, the size changes of your cancer.

DCA Safety and Side Effects

DCA safety and side effects

Sodium dichloroacetate is considered to be a fairly safe alternative cancer treatment. There have been no cases recorded for DCA to be a cause of death.

Before we begin, we should bear in mind that Sodium dichloroacetate has already demonstrated  success in dealing with ‘‘Lactic acidosis in children with congenital mitochondrial defects“  for some time. The first scientific studies and the usage of the drug began over 40 years ago. (Ref.)

In this time period, DCA has been constantly used as a medication for congenital mitochondrial diseases. The research done by Peter Stacpoole and his colleagues proved that when used for therapy, Sodium dichloroacetate can cause nonemild or moderate side effects. (Ref.)

The probability of adverse reactions is dependent on the dosing and the age of the patient. Larger DCA doses and  older patient age (above 40 years) are related to a higher side effect occurrence. (Ref.)

On exceptionally rare occasions, a small portion of the population can metabolize DCA more slowly than the average. For this reason, even the standard DCA doses can cause adverse reactions to appear faster and more prominent in this group of people. In this case, lowering the DCA dose should fix the issues.

If you stop taking DCA, almost all of the side effects disappear in less than a week. The reversible peripheral neuropathy can sometimes take up to 7 or 14 days (rarely) to resolve completely. (Ref.)

According to one of the most famous DCA clinics and their observational data, 44 % of the patients who have taken DCA did not experience side effects.

The most common side effects caused by Dichloroacetate:

▪ Peripheral neuropathy.
(experienced by up to 20% of people who use DCA).

This group of symptoms begins in the fingers, hands and feet. Depending on the intensity of the neuropathy, it can manifest as tingling, numbness, tremor, painful sensations and slightly increased difficulty of coordinated movement.
On less common occasions, neuropathy can emerge in other places and appear as the tingling of eyes, lips and tongue.

Typically, at least a couple of weeks or months are needed for peripheral neuropathy to develop.
This side effect is reversible – its intensity can decrease or it can disappear completely upon lowering the DCA dose or stopping DCA usage. (Ref.)

▪ Sleepiness, mental fogginess, confusion
(experienced by up to 20% of people who use DCA).

This group of symptoms is reversible – you can decrease their intensity or completely make them disappear by lowering the DCA dose or stopping DCA usage.

The rare side effects caused by Dichloroacetate:

▪ Heartburn, nausea, digestive disorders.

Administering Dichloroacetate through the mouth can sometimes cause GI irritability.

▪ Pain at the tumor site (temporary and then resolves).

A very rare adverse reaction. It indicates that due increased apoptosis a lot of cancer cells are dying and indicates that DCA therapy is effective. However, only a couple of Tumor lysis syndrome cases were documented in the most popular DCA administering clinics. This situation is more likely to happen to people who have leukemia, lymphoma or big volume tumors. (Ref.1Ref.2)

▪ Mild liver enzyme (AST, ALT, GGT) elevation, without symptoms.

A majority of medications can cause mild liver enzyme changes in the blood. DCA can cause minimal liver transaminase and transpeptidase elevations (about 50 – 60 U/l) for 1 % of the patients. These little alterations should not cause any worries.
A similar or bigger liver enzyme increase can be influenced by antibiotic, paracetamol (acetaminophen), some types of medicinal herbs and birth control pills. (Ref.)

▪ Increased anxiety, mood changes, hallucinations.

These effects are temporary and should disappear with the discontinued use of DCA. They are more likely to appear in patients that are using drugs which strongly influence the Central nervous system.

Dichloroacetate influence on different organ systems:

▪ DCA and the brain.
If you are currently using cannabinoids, benzodiazepines, opioids or other drugs which affect the Central nervous system, keep in mind that DCA can amplify the adverse reactions caused by these medications (eg. Delirium, memory problems).
This scenario is more likely to happen if the prescriptions have already caused side effects. If the patient is not experiencing any issues with the CNS affecting drugs – the risk for such interactions with DCA is low.

To minimize the probability of these drugs interacting, we recommend starting with low Sodium dichloroacetate doses and to gradually increase them. (Ref.)

▪ DCA and the heart.
Dichloroacetate seems to have a positive effect for the heart function without increasing the additional demand for oxygen. It also improves the efficiency of energy generation in the heart muscle. The drug is safe to use for people with heart failure and increased risk of cardiac ischemia. (Ref.)

▪ DCA and the liver.
In case of liver failure and severe jaundice don’t use high doses of DCA because Dichloroacetate is metabolised in the liver. In situations like these, DCA should be administered intravenously and not through the mouth. (Ref.)

▪ DCA and the kidneys.
Dichloroacetate is safe for patients who have kidney failure. The drug has no toxicity for the kidneys.

▪ DCA and diabetes.
Patients who have diabetes can achieve better blood glycemic control with the help of Dichloroacetate. DCA seems to lower the blood sugar in between meals. (Ref.)

This is the current accurate information on how DCA affects the major organs in the body. We can come to a conclusion that if Dichloroacetate is administered with care and adequate basic knowledge, its health risks are low and can be almost entirely prevented.

We hope this article answers the most important questions.

How DCA Works

For almost half a century, DCA has been a relatively basic substance used for treating people with congenital mitochondrial diseases. Nearly a decade ago, the interest in this drug spiked up because of new research and claims that it could be able to serve those who have cancer. Since then, there has been a lot of interest generated towards this medication.

In this long article, we will attempt to briefly cover what we know about dichloroacetate and how it works. Keep in mind – we‘ll try to explain the complex mechanisms as simply as possible. We encourage every person interested in DCA therapy to read on.

So… How does a small, inexpensive and a relatively nontoxic molecule like dichloroacetate work ?

How cancer cells act differently ?

To better understand the mechanism of DCA, we must be aware of the different processes that thrive in a cancerous cell. Cancer is considered to be a genetic disease in which genes that control how our cells grow and divide start behaving abnormally. Due to error in our DNA, the cells become chaotic, multiply uncontrollably and change their normal metabolic activity.

Every cell contains important organelles called mitochondria. These structures can be called “cellular power plants” because they produce the energy needed for live organisms to function properly. Besides, mitochondria are important in the cells life cycle – they play key roles in activating apoptosis.

Unfortunately, cancer cells have reduced mitochondrial function. This means that cancerous cells mostly produce energy by extremely high rates of glycolysis outside the mitochondria, rather than oxidative phosphorylation inside the mitochondria (Warburg effect) which also causes a massive increase in uptake of glucose and the exhaustion of the patient.

Because of the intracellular metabolic changes apoptosis (natural cell death) is stopped and it makes the malignant cells “immortal”.

Suppressed mitochondrion function leads to a lot of advantages for the tumor – it can survive and grow without oxygen in anaerobic conditions (eg. the cells in the middle of a cancerous mass), it promotes biosynthesis (cancer growth and division), it evades immune cells and disrupts the normal architecture of tissues (the cancer becomes more malignant and dangerous).

On the top of that, the Warburg effect produces an acidic environment. Such conditions damage the intercellular matrix, set the cancerous cells free into the bloodstream or lymph and promote metastasis (the cancer can spread and become deadly).

As we can see, the Warburg effect causes metabolic changes that make cancer a hardly manageable illness. Nevertheless, recently there have been ideas to begin perceiving and approaching cancer as a metabolic disease and this is where the molecule of DCA comes in handy.

How DCA affects cancer ?

So far we can understand how the cellular metabolism of tumors differs from that of our healthy, normal cells. Malignant cells switch off their mitochondria and start producing energy mainly through cytoplasmic glycolysis and these changes generate a lot of advantages for the tumor.

Dichloroacetate works by restoring the suppressed mitochondrial function and rendering the “bad cells” non cancerous. The normalized mitochondria then are able to resume the halted apoptosis process (the natural intracellular suicide system) and the harmful cells start dying on their own. What’s more important, the drug is selective. It doesn’t poison healthy tissues and cause significant effects on non carcinogenic cells like cytotoxic chemotherapy drugs.

The way DCA achieves these results is by reversing the Warburg effect. The substance inhibits an important enzyme which is essential for cancer proliferation – pyruvate dehydrogenase kinase (PDK). Once again the cell starts producing most of its energy in a normal way (through oxidative phosphorylation). The mechanism restores normal cellular metabolic activity.

Notably, Sodium Dichloroacetate has a lot of characteristics of an ideal antitumor therapy. We will discuss these characteristics further.

Why DCA is a good anticancer medication ?

To begin with, as a result of increased apoptosis, the substance effectively stops tumor growth (proliferation) and can even cause them to shrink in size or disappear.

To our surprise, DCA can also reduce the vascularity of tumors (by inhibiting angiogenesis). This prevents the nutrients from reaching and feeding the “bad cells”. Less blood vessel deposition on the cancerous masses also means that there are fewer pathways for cancer to spread – this lowers the probability of metastasis and disease progression.

Last but not least, since dichloroacetate is a small molecule, it crosses the blood-brain barrier and can help manage brain tumors. Currently, there are only few prescriptions that can reach the cerebral matter, making DCA a considerable option for therapy.

However, we are used to the reality that anticancer medications cause severe outcomes. Chemotherapy can have a very harsh effect on the body and provide unpleasant experiences. This is why patients are specifically prepared and receive medications prior to the administration of chemotherapy, to help minimize this

Despite that, DCA isn’t considered to be a cytotoxic chemotherapy drug and it appears to cause minimal systemic toxicity. Dichloroacetate is a gentle non-chemo treatment option that can have none, little or mild side reactions.

Then again, all the side effects are reversible which makes it the most appealing characteristic of using this molecule.

To put in simply, DCA induces intracellular as well as macroscopic changes that can help you accomplish successful therapy against cancer and achieve good improvements. Many people start feeling better in weeks.

What positive improvements people can expect ?

Given the fact that now we understand enough things about this relatively new cancer treatment,  we can turn our attention from a scientific perspective to a more practical point of view. What are the possible experiences when using Sodium Dichloroacetate ?

Bare in mind that the information we present is based on real and open observational data gathered from the clinical practise of top DCA therapy centers in the world. We must remember the main point which is true to every cancer case there is – the earlier the disease is caught and diagnosed, the sooner we take action, the better results we will achieve. The DCA treatment will not always provide positive outcomes and help everyone.

The lowest positive response is disease stabilization. This means that the tumor stops spreading and growing. There are no further signs of cancer progression.

As a result of taking DCA, a much better positive response can be improved symptoms. Patients regain their appetite, feel more energized, reduce their fatigue, regain weight and feel less pain. These things tend to last for a sustained period of time.

More importantly, people suffering from cancer obtain an improvement in blood tests and a reduction of tumor markers.

The best results of using DCA are measurable tumour size reduction or complete cancer remission. DCA users have their tumours screened by imaging techniques such as CT scans,  Magnetic resonance imaging, Ultrasonography and report significant cancer size reduction. Some of them even report complete cancer recovery.

Half of the people who take DCA experience mild side effects that most of the time are neurological and can be improved by a couple of dietary supplements (eg. Vitamin B1Alpha-Lipoic Acid)  or by taking a break from the treatment.

When all the things are considered, we must emphasize that sodium dichloroacetate can be taken alone or in combination with other anticancer medications. Naturally, a lot of people are eager to know – is DCA acceptable with other forms of cancer therapy ?

In short – yes. It is possible and even encouraged (with a couple of exceptions).

New DCA Publication!

TITLE Long-term stabilization of metastatic melanoma with sodium dichloroacetate
AUTHOR(s) Akbar Khan, Doug Andrews, Jill Shainhouse, Anneke C Blackburn
CITATION Khan A, Andrews D, Shainhouse J, Blackburn AC. Long-term stabilization of metastatic melanoma with sodium dichloroacetate. World J Clin Oncol 2017; 8(4): 371-377
URL http://www.wjgnet.com/2218-4333/full/v8/i4/371.htm
DOI http://dx.doi.org/10.5306/wjco.v8.i4.371
OPEN ACCESS This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
CORE TIP Sodium dichloroacetate (DCA) has been studied as a metabolic cancer therapy since 2007. It has been shown that DCA therapy can result in a classic response which is measured by reduction or disappearance of tumours on imaging. However, DCA can also halt cancer cell growth without causing apoptosis (cytostatic effect). This can result in long-term stabilization of metastatic cancer. We present a case of oral DCA therapy resulting in reduction and stabilization of metastatic melanoma in a 32-year-old male for over 4 years, with only minor side effects.
KEY WORDS Dichloroacetate; Cancer; BRAF; Melanoma; Cytostatic
COPYRIGHT © The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
NAME OF JOURNAL World Journal of Clinical Oncology
ISSN 2218-4333
PUBLISHER Baishideng Publishing Group Inc, 7901 Stoneridge Drive, Suite 501, Pleasanton, CA 94588, USA
WEBSITE Http://www.wjgnet.com

CASE REPORT

 

Long-term stabilization of metastatic melanoma with sodium dichloroacetate

 

Akbar Khan, Doug Andrews, Jill Shainhouse, Anneke C Blackburn

 

Akbar Khan, Doug Andrews, Medicor Cancer Centres Inc, Toronto, ON M2N 6N4, Canada

Jill Shainhouse, Insight Naturopathic Clinic, Toronto, ON M4P 1N9, Canada

Anneke C Blackburn, the John Curtin School of Medical Research, the Australian National University, Canberra, ACT 2601, Australia

Author contributions: Khan A treated the patient and wrote most of the case report; Andrews D assisted in development of the natural medication protocol for reduction of DCA side effects, and wrote a portion of the case report; Shainhouse J treated the patient with natural therapy; Blackburn AC interpreted the case report in the context of the literature on in vitro and in vivo DCA research, wrote parts of the introduction and discussion, and reviewed the manuscript overall.

Correspondence to: Akbar Khan, MD, Medical Director, Medicor Cancer Centres Inc, 4576 Yonge St., Suite 301, Toronto, ON M2N 6N4, Canada. akhan@medicorcancer.com

Telephone: +1-416-2270037  Fax: +1-416-2271915

Received: January 30, 2017   Revised: May 5, 2017   Accepted: May 30, 2017

Published online: August 10, 2017

 

Abstract

Sodium dichloroacetate (DCA) has been studied as a metabolic cancer therapy since 2007, based on a pub­lication from Bonnet et al demonstrating that DCA can induce apoptosis (programmed cell death) in human breast, lung and brain cancer cells. Classically, the res­ponse of cancer to a medical therapy in human research is measured by Response Evaluation Criterial for Solid Tumours definitions, which define “response” by the degree of tumour reduction, or tumour disappearance on imaging, however disease stabilization is also a beneficial clinical outcome. It has been shown that DCA can function as a cytostatic agent in vitro and in vivo, without causing apoptosis. A case of a 32-year-old male is presented in which DCA therapy, with no concurrent conventional therapy, resulted in regression and stabilization of re­current metastatic melanoma for over 4 years’ duration, with trivial side effects. This case demonstrates that DCA can be used to reduce disease volume and maintain long-term stability in patients with advanced melanoma.

 

Key words: Dichloroacetate; Cancer; BRAF; Melanoma; Cytostatic

 

Khan A, Andrews D, Shainhouse J, Blackburn AC. Long-term stabilization of metastatic melanoma with sodium dichloroacetate. World J Clin Oncol 2017; 8(4): 371-377  Available from: URL: http://www.wjgnet.com/2218-4333/full/v8/i4/371.htm  DOI: http://dx.doi.org/10.5306/wjco.v8.i4.371

 

Core tip: Sodium dichloroacetate (DCA) has been studied as a metabolic cancer therapy since 2007. It has been shown that DCA therapy can result in a classic response which is measured by reduction or disappearance of tumours on imaging. However, DCA can also halt cancer cell growth without causing apoptosis (cytostatic effect). This can result in long-term stabilization of metastatic cancer. We present a case of oral DCA therapy resulting in reduction and stabilization of metastatic melanoma in a 32-year-old male for over 4 years, with only minor side effects.

 

INTRODUCTION

Sodium dichloroacetate (DCA) caught the attention of the medical community in 2007, when Bonnet et al[1] published the first in vitro and in vivo study illustrating the value of DCA as a metabolic cancer therapy, through its inhibitory action on the mitochondrial enzyme py­ruvate dehydrogenase kinase. Previously, Stacpoole et al[2-4] had published several studies of DCA for the treatment of congenital lactic acidosis in mitochondrial diseases[2-5]. These studies demonstrated that oral DCA is a safe drug for human use. DCA was noted to have an absence of renal, pulmonary, bone marrow and cardiac toxicity[4]. Most DCA side effects were modest, with the most serious one being reversible peripheral neuropathy[6]. Reversible delirium has also been reported[7]. Elevation of liver enzymes (asymptomatic and reversible) has been noted in a small percentage of patients[3]. The prior human research in mitochondrial disorders has enabled the rapid translation of DCA into human use as an off-label cancer therapy. Several reports of clinical trials using DCA as cancer therapy have now been published, confirming its safety profile, and indicating an increasing recognition of the potential usefulness of DCA in the cancer clinic[8-11]. One limitation of these studies involving late stage patients is that they have only reported on treatment for short periods of time.

In Bonnet’s 2007 publication[1], DCA treatment was shown to reduce mitochondrial membrane potential which promoted apoptosis selectively in human cancer cells. Aerobic glycolysis inhibition (the Warburg effect) and mitochondrial potassium ion channel activation were identified as the mechanisms of action of DCA. Further investigations of DCA in vitro have confirmed the anti-cancer activity against a wide range of can­cer types, which have been reviewed recently by Kankotia and Stacpoole[12]. In addition, DCA is also able to enhance apoptosis when combined with other agents[13-15]. Other anticancer actions of DCA have also been suggested, including angiogenesis inhibition[16], alteration of HIF1-a expression[17], alteration of cell pH regulators V-ATPase and MCT1, and other cell survival regulators such as p53 and PUMA[18]. However, many in vitro studies use unreasonably high concentrations of DCA that are not clinically achievable, in an effort to show cytotoxic activity[12]. In other studies, more modest DCA concentrations were used, demonstrating that DCA could be cytostatic. The second report in 2010 of its in vivo anti-cancer activity found DCA alone to be cytostatic in a metastatic model of breast cancer[19], inhibiting proliferation without triggering apoptosis. This suggests a role for DCA as a cancer stabilizer, similar to angiogenesis inhibitors.

In response to the 2007 report of the anti-cancer actions of DCA, Khan began using DCA for the treat­ment of cancer patients with short prognosis or who had stopped responding to conventional cancer therapies. A natural medication protocol was developed in collaboration with a naturopathic physician (Andrews) to address the dose-limiting neurologic toxicity of DCA. This consisted of 3 medicines: Acetyl L-carnitine[20-22], R-alpha lipoic acid[23-25] and benfotiamine[26-28], for neuropathy and encephalopathy prevention. In over 300 advanced stage cancer patients, observational data revealed that DCA therapy benefitted 60%-70% of cases. The neuropathy risk when natural neuro­protective medicines were combined with DCA was approximately 20% using 20-25 mg/kg per day dosing on a 2 wk on/1 wk off cycle (clinic observational data published online at www.medicorcancer.com). Here, a patient case report illustrating both the apoptotic and anti-proliferative effects of chronic DCA treatment over a period of over four years is presented.

 

CASE REPORT

A 32 years old previously healthy fair-skinned male originally noted that a mole on his left calf began to change in 2006. He consulted a doctor and the mole was excised. A pathologic diagnosis of melanoma was made. A sentinel node dissection was carried out, and was negative for metastatic disease. In 2007, the patient noted enlargement of left inguinal lymph nodes, and small melanocytic lesions on the skin of his left leg. He was treated with interferon alpha under a clinical trial at a regional cancer hospital, with reduction of the nodes and resolution of the skin metastases. Interferon was stopped after 9 mo due to side effects.

The patient remained well until 2010, when a new left leg skin metastasis appeared. This was surgically excised. In late 2011, another new cutaneous meta­stasis was identified on the left leg, within the scar from the original melanoma surgery. This was biopsied and a diagnosis of recurrent melanoma was confirmed. He was then treated with wide excision and skin graft.

In March 2012, the patient was diagnosed with a recurrence within the left leg skin graft. This was excised and a new skin graft procedure was performed. Pathology revealed positive margins of the excised metastasis, so a re-excision was performed, again with positive margins. At the same time, needle biopsy of a left inguinal lymph node confirmed the presence of BRAF-positive metastatic melanoma. A Computed tomography (CT) scan performed in Mar 2012 revealed no evidence of distant metastases. The largest left inguinal node was 8mm in diameter, which was reported as “insignificant by size criteria” (Figure 1).

In April 2012, the patient consulted a naturopathic doctor (Shainhouse) and began therapy with the following oral natural anti-cancer agents: Active hexose correlated compound or AHCC (mushroom extract)[29], dandelion root[30], curcumin[31], and astragalus root[32]. Parenteral therapy was also started, which consisted of intravenous vitamin C twice weekly[33] and subcutaneous European mistletoe extract[34]. The patient also changed to a vegan diet.

In May 2012, the patient attended the author’s clinic (Khan) looking to pursue additional non-traditional therapies. DCA therapy was discussed, but the patient decided to give the natural anti-cancer therapies (pre­scribed by Shainhouse) an adequate trial first. CT scan was performed again in May 2012 (after only 1 mo of natural therapy) and indicated mild growth of multiple inguinal and external iliac nodes, with sizes ranging from 10 mm × 11 mm to 14 mm × 15 mm.

In July 2012, CT scan was repeated to assess the patient’s natural anti-cancer therapies. At that time, the left inguinal and external iliac nodes had enlarged again, and ranged in size from 13 mm × 16 mm to 22 mm × 20 mm (Figure 2). PET scan was also performed in preparation for entering a clinical trial in Boston, MA (United States), and confirmed increased glucose uptake in the left inguinal nodes. There was new low intensity (2/10) aching pain in the left inguinal region. Examination revealed a 20 mm non-tender left inguinal lymph node, and two small skin metastases within the left calf skin graft.

The patient was thus diagnosed with disease progression. At that point he decided to initiate DCA therapy. He began oral DCA 500 mg 3 times per day, which was equivalent to 17 mg/kg per day (manufacturer: Tokyo Chemical Industry, United States) in addition to maintaining the other natural therapies. The DCA treatment cycle was 2 wk on and 1 wk off. To minimize the occurrence of DCA side effects, 3 additional natural medications were prescribed: Oral acetyl L-carnitine 500 mg 3 times a day, oral benfotiamine 80 mg twice a day and oral R-alpha lipoic acid 150 mg 3 times a day. These supplements were taken daily (no cycle). Routine baseline blood tests were performed (Table 1). These were all normal, except for low creatinine which was felt to be insignificant.

In November 2012, 4 mo after the addition of DCA to his original natural anti-cancer therapies, the patient was re-assessed. He felt generally well. Two new symptoms were reported to have begun only after initiation of DCA therapy: Slightly reduced sensation of the finger tips and toes, and slightly reduced ability to concentrate during the 2 wk periods in which he was taking DCA. The mild sensory loss was not worsening and was felt to be mild DCA-related neuropathy. Both the numbness and reduced concentration were reported to resolve during the weeks when the patient was off DCA. Blood panel from October 2012 showed no significant changes (Table 1). August 2012 and November 2012 CT scans revealed significant regression of all previously enlarged lymph nodes. The largest node was 10 mm, and there was no evidence of intra-thoracic or intra-abdominal disease, and no bone metastases (Figure 3).

The patient continued to feel well on DCA therapy, and did not notice any new skin metastases or new enlargement of inguinal nodes. He continued to have frequent clinical monitoring with his naturopathic doctor (Shainhouse), and annual follow-up with his medical doctor (Khan). The listed natural anti-cancer therapies (prescribed by Shainhouse) and DCA therapy were maintained into 2016. Blood panel results in June 2016 continued to be normal (Table 1). CT scan was repeated in August 2016, showing no evidence of metastatic melanoma, after a full 4 years of ongoing DCA therapy, combined with natural anti-cancer therapy (Figure 4). By December 2016, the patient reported an increase in work-related stress and a reduction in compliance with his medications. At the time, he noted a new left inguinal mass. Ultrasound imaging was obtained, which revealed a new conglomerate of enlarged lymph nodes measuring 40 mm × 25 mm × 23 mm, with colour Doppler showing blood flow within the mass. This was interpreted as re-growth of melanoma, after approximately four and a half years of continuous DCA therapy. Further workup was performed including a PET/CT scan, which confirmed disease recurrence in 3 left inguinal nodes (SUVmax ranging from 13 to 17.8).

In summary, the patient received conventional therapy for recurrent stage 3 melanoma over a period of 6 years, consisting of primary surgical excision with lymph node dissection, interferon alpha and surgical excisions for recurrent cutaneous metastases on 5 occasions. The patient then received natural anti-cancer therapy alone (prescribed by Shainhouse) for 3 mo with no response, evidenced by steady disease progression on serial CT scans. Finally the patient added oral DCA therapy to the natural anti-cancer therapy, with 3 concurrent neuroprotective medicines (lipoic acid, acetyl L-carnitine and benfotiamine) and no concurrent conventional cancer therapies. The result was a complete radiological remission lasting for over 4 years, followed by recurrence. During the course of DCA therapy, the patient experienced trivial side effects consisting of slight neuropathy and slight reduction of concentration. The patient maintained ECOG level 0 function, and he was able to work full time.

 

DISCUSSION

The use of oral DCA in the metastatic melanoma patient described herein demonstrates tumour shrinkage and long-term disease stability according to clinical status and CT imaging. Disease stability was maintained for over 4 years while taking DCA in the absence of any concurrent conventional therapy, with a survival time since the initial diagnosis of 10 years. According to the National Cancer Institute’s SEER cancer statistics, the survival of this patient who showed no evidence of distant metastases is not remarkable (62.9% 5-year survival rate for melanoma with spread to regional lymph nodes, https://seer.cancer.gov/statfacts/html/melan.html). What is remarkable is that in a situation where involved lymph nodes were clearly enlarging, the addition of oral DCA therapy was efficacious in shrinking the enlarging nodes (Figures 2 and 3), and in achieving a remission lasting over 4 years. It is possible that the natural anti-cancer therapies the patient received synergized with DCA, but it is also clear that these natural therapies alone cannot account for the disease regression. DCA has been reported to have both apoptotic and cytostatic effects[14,17,19,35,36], which is consistent with this patient’s clinical course of regression (apoptotic) and prolonged remission (cytostatic). The recurrence after 4 years coincided with reduced compliance, suggesting that this method of cancer management with DCA requires the metabolic pressure to be maintained continuously. Despite recurrence, the patient remained clinically well and planned to start new immunotherapy medications. It remains to be seen if a change in therapy can once again achieve disease regression or stability.

In addition to the maintenance of remission for over 4 years, this case illustrates that DCA can be well-tolerated in a cancer patient for a prolonged time period, as compared to all published DCA cancer clinical trials. Notably, this patient was able to tolerate 17 mg/kg per day in a regime of 2 wk on/1 wk off for 4 years with minimal side effects. This is similar to our previous case report of chronic DCA usage in colon cancer[37], where the patient was able to tolerate 16 mg/kg per day (but not 25 mg/kg per day) in the same regime, but contrasts with the clinical trials for DCA, which recommend a lower dose of 10-12.5 mg/kg per day given continuously[9,11]. The 1 wk break or the neuroprotective supplements may both contribute to the ability of the patients in the case reports to tolerate the higher dose. Genetic polymorphisms in GSTZ1, the liver enzyme that metabolises DCA, may also contribute to the dose of DCA that can be tolerated[9,38]. Variable drug levels have been reported in the trials, but not all of them have considered this pharmacogenetic aspect of DCA therapy[9,11], and further studies are needed to clarify if this is a significant contributor to DCA tolerance. As of this writing, a DCA multiple myeloma human trial is ongoing, which is examining both GSTZ1 genotypes and drug levels to contribute to our understanding of these issues (Australia New Zealand Clinical Trials Register #ACTRN12615000226505, http://www.anzctr.org.au).

This case report shows that chronic DCA therapy can be used without reducing quality of life, as compared to conventional melanoma therapies such as interferon. To determine the optimal protocol for maximum tolerable acute or chronic treatment with DCA, human trials are needed. But more importantly, it still remains to be clarified what dose is required for on-target effects that will be efficacious against cancer. This information is necessary before investing in larger, long term studies on patient outcomes. DCA deserves further investigation in clinical trials as a non-toxic cancer therapy due to its modest cost and low toxicity, and deserves consideration as an off-label cancer therapy.

 

ACKNOWLEDGMENTS

The authors wish to thank Dr. Humaira Khan for her assistance, and also the patient for his support and consent to publish his case.

 

COMMENTS

Case characteristics

The 32-year-old male patient presented with a pigmented lesion on his leg.

 

Clinical diagnosis

The patient was diagnosed with a melanoma.

 

Laboratory diagnosis

Melanoma confirmed by excisional biopsy.

 

Imaging diagnosis

Enlarged inguinal node confirmed to be involved with melanoma (needle biopsy).

 

Pathological diagnosis

Melanoma, BRAF positive.

 

Treatment

Excision of primary lesion with skin graft, sentinel node dissection, multiple excisions of recurrent cutaneous metastases. Traditional therapy stopped and natural anti-cancer therapies started (AHCC, dandelion root, curcumin, astragalus root, i.v. vitamin C, s.c. European mistletoe). Progression after 3 mo, dichloroacetate (DCA) added. Regression and remission following addition of DCA lasting for over 4 years.

 

Related reports

Computed tomography scan reports demonstrate the course of the disease and response to therapies.

 

Term explanation

DCA: Dichloroacetate sodium; RECIST: Response Evaluation Criteria for Solid Tumours; ECOG: Eastern Cooperative Oncology Group.

 

Experiences and lessons

DCA can act as a pro-apoptotic and cytostatic drug, and can thus achieve regression as well as long-term stabilization of metastatic cancer without serious side effects, as illustrated by this melanoma case.

 

Peer-review

Dr. Khan described a 32-year-old man received DCA therapy, with other medications from natural therapists and maintained in a stabilization state (metastatic melanoma) for over 4 years. It is an interesting case.

 

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FIGURE LEGENDS

Figure 1  Computed tomography scan from March 2012 prior to natural therapies and prior to dichloroacetate therapy. Largest node measured 8 mm in diameter.

Figure 2  Computed tomography scan from July 2012 after 3 mo of natural therapy alone, just prior to the start of dichloroacetate therapy. Largest node measured 22 mm × 20 mm.

Figure 3  Computed tomography scan from November 2012 after 4 mo of dichloroacetate therapy. Largest node measured 10 mm.

Figure 4  Computed tomography scan after 4 years of dichloroacetate therapy without any concurrent conventional cancer therapies. Scan demonstrates absence of cancer re-growth. All nodes measure less than 10 mm.

 

FOOTNOTES

Informed consent statement: The patient described in this manuscript has given consent to publish his case anonymously.

Conflict-of-interest statement: One of the authors (Khan) administers dichloroacetate therapy for cancer patients through Medicor Cancer Centres at a cost, and without profit. The clinic is owned by a family member of this author. The other authors have nothing to disclose.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Manuscript source: Invited manuscript

Peer-review started: February 12, 2017

First decision: March 28, 2017

Article in press: May 31, 2017

P- Reviewer: Su CC    S- Editor: Ji FF    L- Editor: A    E- Editor: Lu YJ 

 

 

 

 

 

 

 

 

 

 

 

 

CASE REPORT

 

Long-term stabilization of metastatic melanoma with sodium dichloroacetate

 

Akbar Khan, Doug Andrews, Jill Shainhouse, Anneke C Blackburn

 

Akbar Khan, Doug Andrews, Medicor Cancer Centres Inc, Toronto, ON M2N 6N4, Canada

Jill Shainhouse, Insight Naturopathic Clinic, Toronto, ON M4P 1N9, Canada

Anneke C Blackburn, the John Curtin School of Medical Research, the Australian National University, Canberra, ACT 2601, Australia

Author contributions: Khan A treated the patient and wrote most of the case report; Andrews D assisted in development of the natural medication protocol for reduction of DCA side effects, and wrote a portion of the case report; Shainhouse J treated the patient with natural therapy; Blackburn AC interpreted the case report in the context of the literature on in vitro and in vivo DCA research, wrote parts of the introduction and discussion, and reviewed the manuscript overall.

Correspondence to: Akbar Khan, MD, Medical Director, Medicor Cancer Centres Inc, 4576 Yonge St., Suite 301, Toronto, ON M2N 6N4, Canada. akhan@medicorcancer.com

Telephone: +1-416-2270037  Fax: +1-416-2271915

Received: January 30, 2017   Revised: May 5, 2017   Accepted: May 30, 2017

Published online: August 10, 2017

 

Abstract

Sodium dichloroacetate (DCA) has been studied as a metabolic cancer therapy since 2007, based on a pub­lication from Bonnet et al demonstrating that DCA can induce apoptosis (programmed cell death) in human breast, lung and brain cancer cells. Classically, the res­ponse of cancer to a medical therapy in human research is measured by Response Evaluation Criterial for Solid Tumours definitions, which define “response” by the degree of tumour reduction, or tumour disappearance on imaging, however disease stabilization is also a beneficial clinical outcome. It has been shown that DCA can function as a cytostatic agent in vitro and in vivo, without causing apoptosis. A case of a 32-year-old male is presented in which DCA therapy, with no concurrent conventional therapy, resulted in regression and stabilization of re­current metastatic melanoma for over 4 years’ duration, with trivial side effects. This case demonstrates that DCA can be used to reduce disease volume and maintain long-term stability in patients with advanced melanoma.

 

Key words: Dichloroacetate; Cancer; BRAF; Melanoma; Cytostatic

 

Khan A, Andrews D, Shainhouse J, Blackburn AC. Long-term stabilization of metastatic melanoma with sodium dichloroacetate. World J Clin Oncol 2017; 8(4): 371-377  Available from: URL: http://www.wjgnet.com/2218-4333/full/v8/i4/371.htm  DOI: http://dx.doi.org/10.5306/wjco.v8.i4.371

 

Core tip: Sodium dichloroacetate (DCA) has been studied as a metabolic cancer therapy since 2007. It has been shown that DCA therapy can result in a classic response which is measured by reduction or disappearance of tumours on imaging. However, DCA can also halt cancer cell growth without causing apoptosis (cytostatic effect). This can result in long-term stabilization of metastatic cancer. We present a case of oral DCA therapy resulting in reduction and stabilization of metastatic melanoma in a 32-year-old male for over 4 years, with only minor side effects.

 

INTRODUCTION

Sodium dichloroacetate (DCA) caught the attention of the medical community in 2007, when Bonnet et al[1] published the first in vitro and in vivo study illustrating the value of DCA as a metabolic cancer therapy, through its inhibitory action on the mitochondrial enzyme py­ruvate dehydrogenase kinase. Previously, Stacpoole et al[2-4] had published several studies of DCA for the treatment of congenital lactic acidosis in mitochondrial diseases[2-5]. These studies demonstrated that oral DCA is a safe drug for human use. DCA was noted to have an absence of renal, pulmonary, bone marrow and cardiac toxicity[4]. Most DCA side effects were modest, with the most serious one being reversible peripheral neuropathy[6]. Reversible delirium has also been reported[7]. Elevation of liver enzymes (asymptomatic and reversible) has been noted in a small percentage of patients[3]. The prior human research in mitochondrial disorders has enabled the rapid translation of DCA into human use as an off-label cancer therapy. Several reports of clinical trials using DCA as cancer therapy have now been published, confirming its safety profile, and indicating an increasing recognition of the potential usefulness of DCA in the cancer clinic[8-11]. One limitation of these studies involving late stage patients is that they have only reported on treatment for short periods of time.

In Bonnet’s 2007 publication[1], DCA treatment was shown to reduce mitochondrial membrane potential which promoted apoptosis selectively in human cancer cells. Aerobic glycolysis inhibition (the Warburg effect) and mitochondrial potassium ion channel activation were identified as the mechanisms of action of DCA. Further investigations of DCA in vitro have confirmed the anti-cancer activity against a wide range of can­cer types, which have been reviewed recently by Kankotia and Stacpoole[12]. In addition, DCA is also able to enhance apoptosis when combined with other agents[13-15]. Other anticancer actions of DCA have also been suggested, including angiogenesis inhibition[16], alteration of HIF1-a expression[17], alteration of cell pH regulators V-ATPase and MCT1, and other cell survival regulators such as p53 and PUMA[18]. However, many in vitro studies use unreasonably high concentrations of DCA that are not clinically achievable, in an effort to show cytotoxic activity[12]. In other studies, more modest DCA concentrations were used, demonstrating that DCA could be cytostatic. The second report in 2010 of its in vivo anti-cancer activity found DCA alone to be cytostatic in a metastatic model of breast cancer[19], inhibiting proliferation without triggering apoptosis. This suggests a role for DCA as a cancer stabilizer, similar to angiogenesis inhibitors.

In response to the 2007 report of the anti-cancer actions of DCA, Khan began using DCA for the treat­ment of cancer patients with short prognosis or who had stopped responding to conventional cancer therapies. A natural medication protocol was developed in collaboration with a naturopathic physician (Andrews) to address the dose-limiting neurologic toxicity of DCA. This consisted of 3 medicines: Acetyl L-carnitine[20-22], R-alpha lipoic acid[23-25] and benfotiamine[26-28], for neuropathy and encephalopathy prevention. In over 300 advanced stage cancer patients, observational data revealed that DCA therapy benefitted 60%-70% of cases. The neuropathy risk when natural neuro­protective medicines were combined with DCA was approximately 20% using 20-25 mg/kg per day dosing on a 2 wk on/1 wk off cycle (clinic observational data published online at www.medicorcancer.com). Here, a patient case report illustrating both the apoptotic and anti-proliferative effects of chronic DCA treatment over a period of over four years is presented.

 

CASE REPORT

A 32 years old previously healthy fair-skinned male originally noted that a mole on his left calf began to change in 2006. He consulted a doctor and the mole was excised. A pathologic diagnosis of melanoma was made. A sentinel node dissection was carried out, and was negative for metastatic disease. In 2007, the patient noted enlargement of left inguinal lymph nodes, and small melanocytic lesions on the skin of his left leg. He was treated with interferon alpha under a clinical trial at a regional cancer hospital, with reduction of the nodes and resolution of the skin metastases. Interferon was stopped after 9 mo due to side effects.

The patient remained well until 2010, when a new left leg skin metastasis appeared. This was surgically excised. In late 2011, another new cutaneous meta­stasis was identified on the left leg, within the scar from the original melanoma surgery. This was biopsied and a diagnosis of recurrent melanoma was confirmed. He was then treated with wide excision and skin graft.

In March 2012, the patient was diagnosed with a recurrence within the left leg skin graft. This was excised and a new skin graft procedure was performed. Pathology revealed positive margins of the excised metastasis, so a re-excision was performed, again with positive margins. At the same time, needle biopsy of a left inguinal lymph node confirmed the presence of BRAF-positive metastatic melanoma. A Computed tomography (CT) scan performed in Mar 2012 revealed no evidence of distant metastases. The largest left inguinal node was 8mm in diameter, which was reported as “insignificant by size criteria” (Figure 1).

In April 2012, the patient consulted a naturopathic doctor (Shainhouse) and began therapy with the following oral natural anti-cancer agents: Active hexose correlated compound or AHCC (mushroom extract)[29], dandelion root[30], curcumin[31], and astragalus root[32]. Parenteral therapy was also started, which consisted of intravenous vitamin C twice weekly[33] and subcutaneous European mistletoe extract[34]. The patient also changed to a vegan diet.

In May 2012, the patient attended the author’s clinic (Khan) looking to pursue additional non-traditional therapies. DCA therapy was discussed, but the patient decided to give the natural anti-cancer therapies (pre­scribed by Shainhouse) an adequate trial first. CT scan was performed again in May 2012 (after only 1 mo of natural therapy) and indicated mild growth of multiple inguinal and external iliac nodes, with sizes ranging from 10 mm × 11 mm to 14 mm × 15 mm.

In July 2012, CT scan was repeated to assess the patient’s natural anti-cancer therapies. At that time, the left inguinal and external iliac nodes had enlarged again, and ranged in size from 13 mm × 16 mm to 22 mm × 20 mm (Figure 2). PET scan was also performed in preparation for entering a clinical trial in Boston, MA (United States), and confirmed increased glucose uptake in the left inguinal nodes. There was new low intensity (2/10) aching pain in the left inguinal region. Examination revealed a 20 mm non-tender left inguinal lymph node, and two small skin metastases within the left calf skin graft.

The patient was thus diagnosed with disease progression. At that point he decided to initiate DCA therapy. He began oral DCA 500 mg 3 times per day, which was equivalent to 17 mg/kg per day (manufacturer: Tokyo Chemical Industry, United States) in addition to maintaining the other natural therapies. The DCA treatment cycle was 2 wk on and 1 wk off. To minimize the occurrence of DCA side effects, 3 additional natural medications were prescribed: Oral acetyl L-carnitine 500 mg 3 times a day, oral benfotiamine 80 mg twice a day and oral R-alpha lipoic acid 150 mg 3 times a day. These supplements were taken daily (no cycle). Routine baseline blood tests were performed (Table 1). These were all normal, except for low creatinine which was felt to be insignificant.

In November 2012, 4 mo after the addition of DCA to his original natural anti-cancer therapies, the patient was re-assessed. He felt generally well. Two new symptoms were reported to have begun only after initiation of DCA therapy: Slightly reduced sensation of the finger tips and toes, and slightly reduced ability to concentrate during the 2 wk periods in which he was taking DCA. The mild sensory loss was not worsening and was felt to be mild DCA-related neuropathy. Both the numbness and reduced concentration were reported to resolve during the weeks when the patient was off DCA. Blood panel from October 2012 showed no significant changes (Table 1). August 2012 and November 2012 CT scans revealed significant regression of all previously enlarged lymph nodes. The largest node was 10 mm, and there was no evidence of intra-thoracic or intra-abdominal disease, and no bone metastases (Figure 3).

The patient continued to feel well on DCA therapy, and did not notice any new skin metastases or new enlargement of inguinal nodes. He continued to have frequent clinical monitoring with his naturopathic doctor (Shainhouse), and annual follow-up with his medical doctor (Khan). The listed natural anti-cancer therapies (prescribed by Shainhouse) and DCA therapy were maintained into 2016. Blood panel results in June 2016 continued to be normal (Table 1). CT scan was repeated in August 2016, showing no evidence of metastatic melanoma, after a full 4 years of ongoing DCA therapy, combined with natural anti-cancer therapy (Figure 4). By December 2016, the patient reported an increase in work-related stress and a reduction in compliance with his medications. At the time, he noted a new left inguinal mass. Ultrasound imaging was obtained, which revealed a new conglomerate of enlarged lymph nodes measuring 40 mm × 25 mm × 23 mm, with colour Doppler showing blood flow within the mass. This was interpreted as re-growth of melanoma, after approximately four and a half years of continuous DCA therapy. Further workup was performed including a PET/CT scan, which confirmed disease recurrence in 3 left inguinal nodes (SUVmax ranging from 13 to 17.8).

In summary, the patient received conventional therapy for recurrent stage 3 melanoma over a period of 6 years, consisting of primary surgical excision with lymph node dissection, interferon alpha and surgical excisions for recurrent cutaneous metastases on 5 occasions. The patient then received natural anti-cancer therapy alone (prescribed by Shainhouse) for 3 mo with no response, evidenced by steady disease progression on serial CT scans. Finally the patient added oral DCA therapy to the natural anti-cancer therapy, with 3 concurrent neuroprotective medicines (lipoic acid, acetyl L-carnitine and benfotiamine) and no concurrent conventional cancer therapies. The result was a complete radiological remission lasting for over 4 years, followed by recurrence. During the course of DCA therapy, the patient experienced trivial side effects consisting of slight neuropathy and slight reduction of concentration. The patient maintained ECOG level 0 function, and he was able to work full time.

 

DISCUSSION

The use of oral DCA in the metastatic melanoma patient described herein demonstrates tumour shrinkage and long-term disease stability according to clinical status and CT imaging. Disease stability was maintained for over 4 years while taking DCA in the absence of any concurrent conventional therapy, with a survival time since the initial diagnosis of 10 years. According to the National Cancer Institute’s SEER cancer statistics, the survival of this patient who showed no evidence of distant metastases is not remarkable (62.9% 5-year survival rate for melanoma with spread to regional lymph nodes, https://seer.cancer.gov/statfacts/html/melan.html). What is remarkable is that in a situation where involved lymph nodes were clearly enlarging, the addition of oral DCA therapy was efficacious in shrinking the enlarging nodes (Figures 2 and 3), and in achieving a remission lasting over 4 years. It is possible that the natural anti-cancer therapies the patient received synergized with DCA, but it is also clear that these natural therapies alone cannot account for the disease regression. DCA has been reported to have both apoptotic and cytostatic effects[14,17,19,35,36], which is consistent with this patient’s clinical course of regression (apoptotic) and prolonged remission (cytostatic). The recurrence after 4 years coincided with reduced compliance, suggesting that this method of cancer management with DCA requires the metabolic pressure to be maintained continuously. Despite recurrence, the patient remained clinically well and planned to start new immunotherapy medications. It remains to be seen if a change in therapy can once again achieve disease regression or stability.

In addition to the maintenance of remission for over 4 years, this case illustrates that DCA can be well-tolerated in a cancer patient for a prolonged time period, as compared to all published DCA cancer clinical trials. Notably, this patient was able to tolerate 17 mg/kg per day in a regime of 2 wk on/1 wk off for 4 years with minimal side effects. This is similar to our previous case report of chronic DCA usage in colon cancer[37], where the patient was able to tolerate 16 mg/kg per day (but not 25 mg/kg per day) in the same regime, but contrasts with the clinical trials for DCA, which recommend a lower dose of 10-12.5 mg/kg per day given continuously[9,11]. The 1 wk break or the neuroprotective supplements may both contribute to the ability of the patients in the case reports to tolerate the higher dose. Genetic polymorphisms in GSTZ1, the liver enzyme that metabolises DCA, may also contribute to the dose of DCA that can be tolerated[9,38]. Variable drug levels have been reported in the trials, but not all of them have considered this pharmacogenetic aspect of DCA therapy[9,11], and further studies are needed to clarify if this is a significant contributor to DCA tolerance. As of this writing, a DCA multiple myeloma human trial is ongoing, which is examining both GSTZ1 genotypes and drug levels to contribute to our understanding of these issues (Australia New Zealand Clinical Trials Register #ACTRN12615000226505, http://www.anzctr.org.au).

This case report shows that chronic DCA therapy can be used without reducing quality of life, as compared to conventional melanoma therapies such as interferon. To determine the optimal protocol for maximum tolerable acute or chronic treatment with DCA, human trials are needed. But more importantly, it still remains to be clarified what dose is required for on-target effects that will be efficacious against cancer. This information is necessary before investing in larger, long term studies on patient outcomes. DCA deserves further investigation in clinical trials as a non-toxic cancer therapy due to its modest cost and low toxicity, and deserves consideration as an off-label cancer therapy.

 

ACKNOWLEDGMENTS

The authors wish to thank Dr. Humaira Khan for her assistance, and also the patient for his support and consent to publish his case.

 

COMMENTS

Case characteristics

The 32-year-old male patient presented with a pigmented lesion on his leg.

 

Clinical diagnosis

The patient was diagnosed with a melanoma.

 

Laboratory diagnosis

Melanoma confirmed by excisional biopsy.

 

Imaging diagnosis

Enlarged inguinal node confirmed to be involved with melanoma (needle biopsy).

 

Pathological diagnosis

Melanoma, BRAF positive.

 

Treatment

Excision of primary lesion with skin graft, sentinel node dissection, multiple excisions of recurrent cutaneous metastases. Traditional therapy stopped and natural anti-cancer therapies started (AHCC, dandelion root, curcumin, astragalus root, i.v. vitamin C, s.c. European mistletoe). Progression after 3 mo, dichloroacetate (DCA) added. Regression and remission following addition of DCA lasting for over 4 years.

 

Related reports

Computed tomography scan reports demonstrate the course of the disease and response to therapies.

 

Term explanation

DCA: Dichloroacetate sodium; RECIST: Response Evaluation Criteria for Solid Tumours; ECOG: Eastern Cooperative Oncology Group.

 

Experiences and lessons

DCA can act as a pro-apoptotic and cytostatic drug, and can thus achieve regression as well as long-term stabilization of metastatic cancer without serious side effects, as illustrated by this melanoma case.

 

Peer-review

Dr. Khan described a 32-year-old man received DCA therapy, with other medications from natural therapists and maintained in a stabilization state (metastatic melanoma) for over 4 years. It is an interesting case.

 

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FIGURE LEGENDS

Figure 1  Computed tomography scan from March 2012 prior to natural therapies and prior to dichloroacetate therapy. Largest node measured 8 mm in diameter.

Figure 2  Computed tomography scan from July 2012 after 3 mo of natural therapy alone, just prior to the start of dichloroacetate therapy. Largest node measured 22 mm × 20 mm.

Figure 3  Computed tomography scan from November 2012 after 4 mo of dichloroacetate therapy. Largest node measured 10 mm.

Figure 4  Computed tomography scan after 4 years of dichloroacetate therapy without any concurrent conventional cancer therapies. Scan demonstrates absence of cancer re-growth. All nodes measure less than 10 mm.

 

FOOTNOTES

Informed consent statement: The patient described in this manuscript has given consent to publish his case anonymously.

Conflict-of-interest statement: One of the authors (Khan) administers dichloroacetate therapy for cancer patients through Medicor Cancer Centres at a cost, and without profit. The clinic is owned by a family member of this author. The other authors have nothing to disclose.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Manuscript source: Invited manuscript

Peer-review started: February 12, 2017

First decision: March 28, 2017

Article in press: May 31, 2017

P- Reviewer: Su CC    S- Editor: Ji FF    L- Editor: A    E- Editor: Lu YJ 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Proof that the cancer industry doesn’t want a cure – even if it’s a pharmaceutical

Tuesday, January 31, 2012 by: PF Louis

http://www.naturalnews.com/034823_cancer_industry_patent_protection_drugs.html

(NaturalNews) A safe and effective cure for cancer has been discovered with a drug that was once used for unusual metabolic problems. Yet, the cancer industry shows no interest with following up on dichloroacetate (DCA) research from University of Alberta in Edmonton, Canada, reported in 2007. That’s because DCA is no longer patented. (1)

That research also confirmed cancer as a metabolic malfunction, not a weird mutation of cells often explained away as a genetic issue. But the medical mafia doesn’t want you to hear about it. But it confirms what most alternative cancer therapists already know.

Since Nixon declared the “war on cancer” in the 1970s, the cancer industry has succeeded with raising money for researching very expensive chemo substances at $50,000 to $100,000 per round or more for toxic therapies that rarely work. (2)

Chemo drugs usually lead to demanding more business with drugs to ease terrible side effects (http://www.naturalnews.com/034761_cancer_drugs_toxicity_Voraxaze.html). Meanwhile, more are getting cancer and more are dying from it, mostly because of the toxic treatments.

Explaining DCA research results

Evangelos Michelakis and the Alberta University research team tested DCA on human cancer cells outside the body and in cancerous mice with profound success. DCA was once used for unusual metabolic disorders. The worst side effects, which rarely occur, include some numbness and an affected gait.

The mice were fed DCA in water, and in weeks they had remarkable tumor shrinkage. This indicates DCA can be taken orally. DCA works by restoring the cells’ mitochondria. Michelakis and his team had discovered that the mitochondria in cancer cells are not permanently damaged and irreparable. This is what mainstream medicine thinks.

With mitochondria malfunctioning, cancer cells use glucose fermentation for survival energy. This fermentation occurs when glycolysis (glucose conversion) occurs in an anaerobic cellular environment, which can be created by benign tumor masses, toxins, and low pH levels.

DCA restores mitochondria in cells to make them function properly. Another function of normal mitochondria is signaling apoptosis, or cellular self destruction. Normal cells die and become replaced constantly. But with cancer cells, the apoptosis signal is nullified, making cancer cells “immortal.” (3)

The Alberta University researchers also realized that glycolysis fermentation in cancer cells produces lactic acid. The lactic acid breaks down the collagen holding those cells together in a tumor. This allows cancer cells to easily break away from a tumor shrinking with mainstream therapies.

The researchers reasoned this is why cancer metastasizes or spreads to different parts of the body or reappears after remission from chemo.

Tragic hypocrisy

Alternative cancer therapies have little or no problem with metastatic cancer or even cancer reoccurring after remission. Most alternative cancers simply cure cancers completely.

DCA offers the cancer industry an opportunity to come up with a pharmaceutical cure that is much cheaper and safer than their current standard of care. Yet the cancer industry is ignoring this opportunity. Instead, DCA is a homeless orphan begging for research funds to avoid legal issues with off label use on cancer. (4)

Alternative cancer practitioners have always simply tried out and when they succeeded shared them with others who cared more about healing than money and power.

The medical mafia has created a matrix that demands big bucks to make big bucks for sick care instead of curing. Everyone in on the scam makes out financially. The cancer industry accuses alternative cancer therapists of quackery and taking advantage of the desperately ill for financial gain. Accusing others of your motives and crimes is called projection.

The medical/pharmaceutical complex is crony capitalism that doesn’t want a cure for cancer from anywhere.

Sources for this article include:

(1) http://www.newscientist.com/article/dn10971

(2) http://www.sawilsons.com/gonzalez2.htm

(3) http://www.cell.com/cancer-cell/retrieve/pii/S1535610806003722

(4) http://www.dca.med.ualberta.ca/Home/Donations/

Chemotherapies that target angiogenesis can increase metastasis threefold- Cancer Cell Journal

Study finds that tumor cells can prevent cancer spread

January 17, 2012 in Cancer Cell Journal

http://medicalxpress.com/news/2012-01-tumor-cells-cancer.html

A new study finds that a group of little-explored cells in the tumor microenvironment likely serve as important gatekeepers against cancer progression and metastasis. Published in the January 17 issue of Cancer Cell, these findings suggest that anti-angiogenic therapies – which shrink cancer by cutting off tumors’ blood supply – may inadvertently be making tumors more aggressive and likely to spread.

One approach to treating cancer targets angiogenesis, or blood vessel growth. In this new investigation, senior author Raghu Kalluri, MD, PhD, Chief of the Division of Matrix Biology at Beth Israel Deaconess Medical Center (BIDMC) and Professor of Medicine at Harvard Medical School (HMS), wanted to find out if targeting a specific cell type, the pericyte, could inhibit tumor growth in the same way that other antiangiogenic drugs do. Pericytes are an important part of tissue vasculature, covering blood vessels and supporting their growth. Kalluri and his colleagues began by creating mice genetically engineered to support drug-induced depletion of pericytes in growing tumors. They then deleted pericytes in implanted mouse breast cancer tumors, decreasing pericyte numbers by 60 percent. Compared with wild-type controls, they saw a 30 percent decrease in tumor volumes over 25 days. However, contrary to conventional clinical wisdom, the investigators found that the number of secondary lung tumors in the engineered mice had increased threefold compared to the control mice, indicating that the tumors had metastasized. “If you just looked at tumor growth, the results were good,” says Kalluri. “But when you looked at the whole picture, inhibiting tumor vessels was not controlling cancer progression. The cancer was, in fact, spreading.” To understand the mechanism behind this increased metastasis, Kalluri and his team examined the tumor’s microenvironment to find out what changes were taking place at the molecular level. They found a fivefold percentage increase in hypoxic areas in tumors lacking pericytes. “This suggested to us that without supportive pericytes, the vasculature inside the tumor was becoming weak and leaky—even more so than it already is inside most tumors—and this was reducing the flow of oxygen to the tumor,” explains Kalluri. “Cancer cells respond to hypoxia by launching genetic survival programs,” he adds. To that end, the investigators found evidence of epithelial-to-mesenchymal transition (EMT), a change that makes the cells more mobile, so they can travel through those leaky vessels to new locations, and makes them behave more like stem cells, so they are better able to survive. Experiments that demonstrated fivefold increases in protein markers of EMT showed that the cells had undergone the change. The team also found a fivefold increase in activation of Met, a receptor molecule that promotes cell migration and growth.

Importantly, the team found that these molecular changes occurred inside the smaller, pericyte-depleted tumors that had increased incidences of secondary tumors in the lungs in the mouse models. “This suggested that smaller tumors are shedding more cancer cells into the blood and causing more metastasis,” says Kalluri. “We showed that a big tumor with good pericyte coverage is less metastatic than a smaller tumor of the same type with less pericyte coverage.” Because cancer therapies such as Imatinib, Sunitinib and others have been shown to decrease pericytes in tumors, the researchers’ next step was to perform the same experiments in mice with primary tumors, only this time, using Imatinib and Sunitinib rather than genetic programs to decrease pericyte numbers. And while both Imatinib and Sunitinib caused a 70 percent pericyte depletion, the end results, stayed the same: metastasis increased threefold. “We showed that a big tumor with good pericyte coverage is less metastatic than a smaller tumor of the same type with less pericyte coverage,” says Kalluri, who corroborated these findings in multiple types of cancer by repeating these same experiments with implanted renal cell carcinoma and melanoma tumors. Additional experiments showed that combining pericyte-depleting drugs with the Met-inhibiting drug helped suppress EMT and metastasis. Finally, to determine if the findings were relevant to patients, the scientists examined 130 breast cancer tumor samples of varying cancer stages and tumor sizes and compared pericyte levels with prognosis. They found that samples with low numbers of pericytes in tumor vasculature and high levels of Met expression correlated with the most deeply invasive cancers, distant metastasis and 5- and 10- year survival rates lower than 20 percent. “These results are quite provocative and will influence clinical programs designed to target tumor angiogenesis,” says Ronald A. DePinho, president of the University of Texas MD Anderson Cancer Center. “These impressive studies will inform and refine potential therapeutic approaches for many cancers.” Meanwhile, for Kalluri, the work suggests that certain assumptions about cancer must be revisited. “We must go back and audit the tumor and find out which cells play a protective role versus which cells promote growth and aggression,” says Kalluri. “Not everything is black and white. There are some cells inside a tumor that are actually good in certain contexts.” Provided by Beth Israel Deaconess Medical Center

Read more at: http://medicalxpress.com/news/2012-01-tumor-cells-cancer.html#jCp

Surgery – Biopsies Cause Metastasis – New Study finds

PROOF THAT CANCER SURGERY INCREASES MORTALITY

Walter Last

It is generally accepted in cancer research that the vast majority of patients or about 90% die from metastases or secondary tumours, and only a small minority from a primary tumour. Therefore it should be of great concern to therapists as well as patients that already more than 30 years ago it was conclusively shown that cancer surgery is the main cause of metastasis (Krokowski, see below). However, this research was completely ignored by the profession, it was just too awful to contemplate, and patients never got to know about it (1).

Since then more and more disturbing data and reviews have been published, the latest one is a comprehensive review by an international team of leading cancer researchers with the conclusion obvious from the title: Surgery Triggers Outgrowth of Latent Distant Disease in Breast Cancer: An Inconvenient Truth? (2).

Because of the undisputed status of the members of this team, their conclusions can no longer be ignored by the medical profession and cause much consternation, especially as the review is an open access publication. I expect that efforts are being made to prevent this information from becoming widespread public knowledge.

The review also found that future organ metastasis is independent of the size of the primary tumour and its apparent malignancy or the involvement of any lymph glands. Metastasis seems to depend mainly on the degree of stress for the tumour and the patient, growth stimulation due to the wound-healing mechanism initiated by surgery as well as on the quality of the immune system.

Furthermore, as the following examples show, surgery is not the only medical procedure that increases metastasis. In recent years there has been a steady stream of research showing that basically all medical interventions can trigger metastasis while a growing number of natural remedies and methods tend to inhibit metastasis.

Recent research findings

While most cancer research is funded by drug companies with the aim of increasing their profits, there are now also a growing number of independent studies that show the negative side of conventional cancer therapy. Here is a small selection of interesting research findings.

Conflict of Interest in Cancer Research: This analysis shows why it is so difficult to get to the truth in medical research. Conflicts of interest exist in a considerable number of cancer research articles published in medical journals, and there is a high degree of financial connections between researchers and pharmaceutical companies. This produces biased results with a more favourable outcome for investigated drugs and technologies (3).

Experts want to stop screening: Screening for breast and prostate cancer has not brought a decline in deaths from these diseases. Instead screening programs lead to tumour over-detection and over-treatment (4).

Morphine stimulates cancer and shortens life: Morphine has been used in cancer treatment for two centuries. Now research shows that it stimulates the growth and spread of cancer cells and shortens the survival time of patients (5).

Diagnostic X-rays cause cancer: It has been estimated that diagnostic X-rays over a lifetime cause up to 3.2% additional cancers in a population. Germany ranks among the countries with the highest X-ray cancer rates while with 0.6% the U.K. and Poland have the lowest lifetime risk, in Australia it is 1.3% (6).

Radiation therapy damages bones: The scientific world has been shaken by a report that a single therapeutic dose of radiation can cause appreciable bone loss. Years later osteoporosis, bone necrosis or bone cancer may develop (7).

More radiation danger: Exposure to ionizing radiation is known to result in genetic damage that can make cells cancerous. Now a new study has revealed that radiation can alter the environment surrounding cells so that future cells are more likely to become cancerous (8).

Chemotherapy promotes metastasis: Taxol, a chemotherapy drug, causes cancer cell micro-tentacles to grow longer and tumour cells to reattach faster. If treated with taxol before surgery to shrink the primary tumour, levels of circulating tumour cells go up 1,000 to 10,000 fold, potentially increasing metastasis (9).

Tamoxifen increases aggressive tumours: Tamoxifen use for breast cancer patients decreases their risk of developing a more common and less dangerous type of second breast cancer but has a more than four-fold increased risk of causing a more aggressive and deadly tumour (10).

Biopsies cause metastases: Biopsies may actively encourage the spread of metastases. Needle biopsies caused a 50% increase of metastatic spread to nearby lymph glands of breast tumours as compared to lumpectomies (11).

Stress promotes cancer: Stress hormones protect cancer cells from self destruction, promote the spread and growth of tumours directly as well as indirectly by weakening the immune system and encouraging new blood vessel growth. Patient stress  was associated with faster disease progression (12).

Stress kills: Stress hormones are released in high amounts with fear and during surgery. They greatly impair the immune system and promote the spread of metastases. Blocking stress hormones increased long-term post-operative cancer survival rates in animal models by 200-300 percent (13).

Breast cancer metastasis after hormone replacement therapy: Previously it had been shown that hormone replacement therapy increases the risk of breast cancer. Now a new study has found that it also increases the chance of the cancer metastasizing, or spreading to the lymph nodes (14).

Sharp drop in breast cancer rates: In recent years breast cancer rates dropped sharply due to a corresponding sharp drop in the use of hormone replacement therapy (15).

Ernst KrokowskiErnst H. Krokowski, M.D., Ph.D. (1926 – 1985) was a German Professor of Radio­logy. His research provided the first convincing proof that cancer surgery triggers metastasis. While many of his articles on different subjects are still on public record, his research on the relationship between surgery and metastases is difficult to find, even in German. His only paper on this subject in English is not listed in PubMed, and the journal in which it was published does no longer exist (16). Because of the obvious importance of this research I have now made this article available on my website (1). Also a related lecture in German can still be downloaded (17).

The Summary of his article reads: ‘It can no longer be doubted that under certain conditions diagnostic or surgical procedures can result in metastases. Analysis of metastatic growth rates has shown that from 30 percent (in hypernephroma) to 90 percent (in sarcoma and seminoma) of the diagnosed metastases were provoked by such procedures. This has been established by numerous animal experiments and clinical observations, and necessitates a change in the currently held concept of cancer therapy. The previ­ously applied and proven treatments by surgery and radiation must be preceded by a metastasis prophylaxis. Three different ways to achieve such a prophylaxis are proposed.’

With radiological imaging he measured the growth rates of 2,893 metastatic tumours in 568 patients with different cancers. From these he derived the following conclusions:

 

<!–[if !supportLists]–> 1.     <!–[endif]–> Metastases arise only from primary tumours or from their local recurrences; they disseminate at one time or only in a few shoves.

 

<!–[if !supportLists]–> 2.     <!–[endif]–> Lymph node metastases behave biologically differ­ently from organ metastases [lymph node metastases are relatively harmless, organ metastases are very dangerous].

 

<!–[if !supportLists]–> 3.     <!–[endif]–> The more than 3,000 growth curves (including exper­imental data from animals) can be described by a growth formula. The growth curves of a very large number of meta­stases, from 30 to 90 percent depending on the type of tumour, can be traced back to the time of the first treatment.

 

Here are some key observations from his article:

 

<!–[if !supportLists]–> §  <!–[endif]–> Inflated success rates [of cancer surgery] are the result of either selective composition of the groups of patients studied or of correspondingly adapted, i.e., corrected, statistics.

 

<!–[if !supportLists]–> §  <!–[endif]–> Cures related to the same stage and tumour size have not improved in the last 20 to 25 years [more recent findings state that the cure rate has not significantly increased since the 1970’s, which means that overall there was no significant improvement since the 1950’s].

 

<!–[if !supportLists]–> §  <!–[endif]–> Untreated postmenopausal women with breast cancer live longer than medically treated patients.

 

<!–[if !supportLists]–> §  <!–[endif]–> Metasta­ses occur sooner in fast-growing tumours than in slow-growing tumours. This suggests that these metastases begin their development at the same time as the first treatment.

 

<!–[if !supportLists]–> §  <!–[endif]–> Present cancer surgery may be regarded as a second Semmelweis phenomenon! (Dr Semmelweis campaigned for surgeons to wash and disinfect  their hands to stop them killing women during childbirth).

 

<!–[if !supportLists]–> §  <!–[endif]–> Manipulation of a tumour, such as severe palpation and pressure [mammography!], biopsy or surgery, results in a sudden increase of tumour cells released into the blood with a higher probability of metastasis.

 

<!–[if !supportLists]–> §  <!–[endif]–> The connection between surgery and formation of metastases was particularly impressive in single observed cases: in a patient with a sarcoma, formation of metastases occurred after surgery of the primary tumour and each time after four further surgeries of locally recurrent tumours.

 

<!–[if !supportLists]–> §  <!–[endif]–> It has long been taught in medicine that a melanoma should not be injured since lesions would cause an almost explosion-like growth of metastases.

 

<!–[if !supportLists]–> §  <!–[endif]–> Not only disturbance of a tumour but also unrelated surgery at a different location can trigger metastasis.

 

<!–[if !supportLists]–> §  <!–[endif]–> The larger a tumour becomes the slower its growth, and some observations suggest that it eventually stops growing.

 

<!–[if !supportLists]–> §  <!–[endif]–> Radiation and chemotherapy of the tumour before and after surgery were both unsuccessful.

 

<!–[if !supportLists]–> §  <!–[endif]–> The chance to decisively improve the cure quota occurs only once during the course of cancer, namely at the time of the first treatment.

 

An Inconvenient Truth?

 

The following review cites a steady stream of studies showing that it is better for patients to leave tumours alone. But that is not in the interest of the cancer industry for which invasive treatment is the financial life-blood. There were always new drugs and new ways to combine chemotherapy and radiotherapy with surgery, and claims that now a way has been found to prolong the lives of  patients. With new methods of early detection and small, precancerous, non-invasive and dormant tumours classified as cancer—tumours that would not have become malignant if left alone—some statistics indeed showed improved cure rates. This has now changed with a comprehensive review by this international team of leading cancer researchers.

Michael Retsky, Romano Demicheli, William Hrushesky, Michael Baum and Isaac Gukas

Review:Surgery Triggers Outgrowth of Latent Distant Disease in Breast Cancer: An Inconvenient Truth?

Cancers 2010, 2(2), 305-337; doi:10.3390/cancers2020305

Received: 9 March 2010; in revised form: 25 March 2010 / Accepted: 26 March 2010 / Published: 30 March 2010

Here is the Abstract of Surgery Triggers Outgrowth of Latent Distant Disease in Breast Cancer: An Inconvenient Truth? (2):

‘We review our work over the past 14 years that began when we were first confronted with bimodal relapse patterns in two breast cancer databases from different countries. These data were unexplainable with the accepted continuous tumour growth paradigm. To explain these data, we proposed that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell phase and the avascular micrometastasis phase. We also suggested that surgery to remove the primary tumour often terminates dormancy resulting in accelerated relapses. These iatrogenic events are apparently very common in that over half of all metastatic relapses progress in that manner. Assuming this is true, there should be ample and clear evidence in clinical data. We review here the breast cancer paradigm from a variety of historical, clinical, and scientific perspectives and consider how dormancy and surgery-driven escape from dormancy would be observed and what this would mean. Dormancy can be identified in these diverse data but most conspicuous is the sudden synchronized escape from dormancy following primary surgery. On the basis of our findings, we suggest a new paradigm for early stage breast cancer. We also suggest a new treatment that is meant to stabilize and preserve dormancy rather than attempt to kill all cancer cells as is the present strategy.’

http://www.mdpi.com/journal/cancers/special_issues/induced_angiogenesis

The bimodal relapse patterns referred to in this abstract mean that there are two time peaks when metastases appear after surgery for the primary tumour. The first peak is after 18 months, then follows a dip at 50 months and a broad peak at 60 months with a long tail extending for 15 to 20  years. About 50 to 80% of all relapses are in the first peak. Patients with large tumours relapse mainly in the first peak while with smaller tumours relapses are equal in both peaks.

 

There is also a structure in the first peak. Relapses in the first 10 months are due to micro-metastases that pre-exist with the primary tumour and that are stimulated to grow. This mode is most common for premenopausal patients with positive lymph nodes, over 20% of whom relapse. The rest of the first peak is due to single cells that are initially dormant but are induced to divide as a result of surgery. The second peak is then due to single cancer cells that have been seeded during surgery and are subsequently gradually developing into metastases.

 

This dynamic also accounts for the persistent excess mortality of premenopausal women in the third year of long-term mammography screening trials: metastases appear after 10 months and the time between relapse and death in breast cancer is approximately 2 years, which then results in death about 3 years after screening. I remember a young and apparently healthy patient who just had her breast removed after a mammogram showed a tiny tumour. She was confident that she had been saved because it had been caught so early, but 3 years later she was dead.

 

Other interesting evidence in this paper is from a Danish report: forensic autopsies show that 39% of women aged 40–49 have hidden and dormant breast cancer, while the lifetime risk of clinical breast cancer in Denmark is only 8%. This means that only about 20% of positive mammograms are for real and would have progressed to a clinical stage. The rest are either completely harmless and boost the medical cure rate, or in others subsequent surgery does trigger metastases and these women eventually die due to their treatment.

 

Here are some more highlights from this article:

 

<!–[if !supportLists]–> §  <!–[endif]–> Getting women screened with mammography is a major goal of some organizations so this information (about possible harm) is withheld as its release will be contrary to achieving their goal.

 

<!–[if !supportLists]–> §  <!–[endif]–> During most of the 20th century radical mastectomy was the accepted therapy. Unfortunately, only 23% of patients survived 10 years. The natural response to this failure was even more radical surgery.

 

<!–[if !supportLists]–> §  <!–[endif]–> The next step by medical oncologists was similar to that by surgeons: if a little doesn‘t work then try a lot! Needless to say the high dose chemotherapy with bone marrow rescue was a failure and the least said about this sorry episode in the history of breast cancer the better.

 

<!–[if !supportLists]–> §  <!–[endif]–> Pathological and autopsy studies have suggested that most of the occult tumours in breast (and prostate cancers) may never reach clinical significance.

 

<!–[if !supportLists]–> §  <!–[endif]–> Cancer cells and micro-metastases remain in a state of dormancy until some signal, perhaps the act of surgery or other adverse life event (emotional shock according to Dr Hamer) stimulates them into fast growth. The act of wounding the patient creates a favorable environment for the sudden transfer of a micro-metastasis from a latent to an active phase.

 

<!–[if !supportLists]–> §  <!–[endif]–> A large primary tumour inhibits the development and growth of any distant metastases! Removal of the primary results in the establishment and rapid growth of large numbers of latent metastases, the majority of which would have remained dormant or would have disappeared if the primary tumour had not been removed. The growth-stimulating postoperative effects on pre-existing latent metastases are due to removal of the primary tumour.

 

<!–[if !supportLists]–> §  <!–[endif]–> Other cancers also need to be carefully examined. There are data showing similar activity especially in melanoma and osteosarcoma.

References

 

<!–[if !supportLists]–> 1)     <!–[endif]–> http://www.health-science-spirit.com/Krokowski.pdf

 

<!–[if !supportLists]–> 2)     <!–[endif]–> http://www.mdpi.com/2072-6694/2/2/305/pdf, 30 March 2010

 

<!–[if !supportLists]–> 3)     <!–[endif]–> http://www.eurekalert.org/pub_releases/2009-05/acs-rfc050609.php, 11 May 2009

 

<!–[if !supportLists]–> 4)     <!–[endif]–> http://esciencenews.com/articles/2010/03/24/study.questions.whether.screening.really.cuts.breast.cancer.deaths, 24 March 2010, http://www.sciencedaily.com/releases/2009/10/091020181301.htm, 22 October 2009, and http://scienceblog.com/35676/implementing-comparative-effectiveness-research-lessons-from-the-mammography-screening-controversy/ 22 June 2010

 

<!–[if !supportLists]–> 5)     <!–[endif]–> http://www.sciencedaily.com/releases/2009/11/091118143209.htm, 18 November 2009

 

<!–[if !supportLists]–> 6)     <!–[endif]–> http://www.abc.net.au/science/news/stories/s1034306.htm, 30 January 2004

 

<!–[if !supportLists]–> 7)     <!–[endif]–> http://www.cancerdecisions.org/102906_page.html, 29 October 2006

 

<!–[if !supportLists]–> 8)     <!–[endif]–> http://www.physorg.com/news192978184.htm, 13 May 2010

 

<!–[if !supportLists]–> 9)     <!–[endif]–> http://www.sciencedaily.com/releases/2010/03/100312133712.htm, 15 March 2010

 

<!–[if !supportLists]–> 10)  <!–[endif]–> http://www.medicalnewstoday.com/articles/161850.php, 26 August 2009

 

<!–[if !supportLists]–> 11)  <!–[endif]–> http://articles.mercola.com/sites/articles/archive/2005/04/16/needle-biopsy.aspx, 16 April 2005

 

<!–[if !supportLists]–> 12)   <!–[endif]–> http://www.scientificamerican.com/article.cfm?id=does-stress-feed-cancer, 13 April 2010

 

<!–[if !supportLists]–> 13)   <!–[endif]–> http://scienceblog.com/15572/stress-fear-increase-cancer-recurrence-risk-study-says/, 27 February 2008

 

<!–[if !supportLists]–> 14)  <!–[endif]–> http://www.medicalnewstoday.com/articles/188001.php, 07 May 2010

 

<!–[if !supportLists]–> 15)  <!–[endif]–> http://breast-cancer-research.com/content/12/1/R4, 8 January 2010

 

<!–[if !supportLists]–> 16)  <!–[endif]–> Krokowski, E.H.: Is the Current Treatment of Cancer Self-Limiting in the Extent of its Success? J Int Acad Preventive Medicine, 6 (1) 23 – 39, 1979

 

<!–[if !supportLists]–> 17)  <!–[endif]–> http://www.windstosser.ch/museum/manuskript/allgem_u_historisch/05_7.html –  Krokowski, E,H.: Verändertes Konzept der Krebsbehandlung. Lecture at the ‘Kongress der DEUTSCHEN AKADEMIE FÜR MEDIZINISCHE FORTBILDUNG 1978 in Kassel’

 

<!–[if !supportLists]–> 18)  <!–[endif]–> http://www.cancerdecisions.com/031509_page.html, 15 March 2009

 

<!–[if !supportLists]–> 19)  <!–[endif]–> http://www.medicalnewstoday.com/articles/23042.php, 19 April 2005

 

<!–[if !supportLists]–> 20)  <!–[endif]–> http://www.sanfordburnham.org/default.asp?contentID=785, 15 September 2009

 

<!–[if !supportLists]–> 21)  <!–[endif]–> http://www.curenaturalicancro.com/pdf/bicarbonate-increases-tumour-ph-and-inhibits-metastases.pdf, 10 March 2009

 

<!–[if !supportLists]–> 22)  <!–[endif]–> http://www.sciencedaily.com/releases/2010/03/100309182449.htm, 10 March 2010

 

<!–[if !supportLists]–> 23)  <!–[endif]–> http://scienceblog.com/10094/ginkgo-biloba-extract-more-than-just-for-memory/,24 February 2006

 

<!–[if !supportLists]–> 24)  <!–[endif]–> http://www.medicalnewstoday.com/articles/167261.php, 14 October 2009

 

<!–[if !supportLists]–> 25)  <!–[endif]–> http://www.scientificamerican.com/article.cfm?id=environment-as-cause-for-cancer, 6 May 2010

 

<!–[if !supportLists]–> 26)  <!–[endif]–> http://www.newscientist.com/article/dn18799-rats-on-junk-food-pass-cancer-down-the-generations.html, 20 April 2010

 

<!–[if !supportLists]–> 27)  <!–[endif]–> http://www.medicinenet.com/script/main/art.asp?articlekey=104326, 4 August 2009

 

<!–[if !supportLists]–> 28)  <!–[endif]–> http://cancerres.aacrjournals.org/cgi/content/full/67/3/847, 1 February 2007, and also http://www.sciencedaily.com/releases/2010/05/100509144652.htm, 9 May 2010

 

<!–[if !supportLists]–> 29)  <!–[endif]–> http://scienceblog.com/20646/autoantibodies-may-be-created-in-response-to-bacterial-dna/, 27 April 2009

 

<!–[if !supportLists]–> 30)  <!–[endif]–> http://www.sciencedaily.com/releases/2009/06/090611160658.htm, 11 June 2009

 

<!–[if !supportLists]–> 31)  <!–[endif]–> http://foodforbreastcancer.com/news/fasting-protects-normal-cells-and-sensitizes-cancer-cells-to-chemotherapy, 6 May 2010

 

<!–[if !supportLists]–> 32)  <!–[endif]–> Last, Walter: The Holistic Solution to Overcoming Cancer. NEXUS 2008; 16(1); also at http://www.health-science-spirit.com/cancersolution.htm

 

<!–[if !supportLists]–> 33)  <!–[endif]–> http://www.wired.com/wiredscience/2009/05/cancercompromise/

 

<!–[if !supportLists]–> 34)  <!–[endif]–> Websites: http://www.health-science-spirit.com/, www.heal-yourself.com.au or www.healing-yourself.com. Books: Overcoming Cancer http://www.the-heal-yourself-series.com/OvercomingCancer.html, and Heal Yourself the Natural Way http://www.the-heal-yourself-series.com/Heal_Yourself_The_Natural_Way.html

 

http://www.health-science-spirit.com/cancersurgery.htm

Dichloroacetate reduces sympathetic nerve responses to static exercise

Dichloroacetate reduces sympathetic nerve responses to static exercise

  1. 1.  S. Ettinger,
  2. 2.  K. Gray,
  3. 3.  S. Whisler, and
  4. 4.  L. Sinoway

+ Author Affiliations

1.   1Milton S. Hershey Medical Center, Division of Cardiology, PennsylvaniaState University, Hershey 17033.

Abstract

Lactic acid is thought to be a stimulant of muscle metaboreceptors. The goal of the present study was to determine if inhibition of lactic acid production by dichloroacetate (DCA) would attenuate muscle sympathetic nerve activity (MSNA) during static forearm exercise. DCA increases pyruvate dehydrogenase levels. Thus, for a given amount of pyruvate produced, less lactic acid is formed. Seven subjects performed static forearm exercise at 20% maximal voluntary contraction until fatigue followed by posthandgrip circulatory arrest (PHG-CA) (trial.1). Subjects then received DCA (35 mg/kg) and repeated the exercise protocol (trial 2). We observed an attenuated rise in forearm venous lactate and MSNA. The trial 2 MSNA value during PHG-CA was 51 +/- 11% less than the value during trial 1 (P less than 0.01). In seven control subjects, two bouts of static forearm exercise were performed with an intervening saline infusion. This intervention had no effect on lactate or MSNA responses to exercise. We conclude that DCA attenuates lactate responses to static exercise, and this is associated with a blunted MSNA response.