Surviving Terminal Cancer – A Patient Advocacy Film
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Surviving Terminal Cancer – A Patient Advocacy Film

In 1971, when President Nixon declared
war on cancer, 1 in 30 of us would develop cancer in our lifetime. Today that figure
is 1 in 3. Conversely, the cold fact is that despite
trillions being spent on research, we have not cured a single cancer since the 1970s.
If this is a war on cancer, then we are staring defeat in the face. We are little closer to
overcoming metastasis or malignancy, the holy grails of oncology, than we were 50 years
ago. Is it possible that a tiny colony of malignant brain cancer survivors, the most
deadly of all cancers, hold the key to a dramatic improvement in all cancer therapies tomorrow?
Could the next great stride forward in the field of oncology be simply a change in strategy
as opposed to a new drug or technology? And what happens if that change in approach directly
contravenes established medical practice, and the entire clinical trial structure we
have built for testing cancer treatments? I think that many of these brain
tumours and other kinds of cancers are treatable. I just think that a mountain of evidence is
being over looked. If you face this disease and say
from the get go that it is incurable, you will always be right, all your patients will
die, and you have no business treating those patients in the first place. They’re trying to protect people.
They inadvertently get into a situation where they kill people. I would not be alive today if I
had listened to the only to the advice of my oncologist. Because as one point he told
me that, Well, you should try to consider just staying home now and playing with your
little daughter while you can and not pursue any aggressive treatments – but I decided otherwise. 02:32Surviving Terminal Cancer When you have just been diagnosed with terminal
cancer, a cancer for which there is no known cure available, access to experimental treatments
becomes the last refuge of hope. but what most people are unaware of, until they themselves
are touched by cancer, is how patients are routinely denied access to those treatments
acknowledged as holding the only possible chance of extending their life The Everest of oncology The brain poses unique challenges
for clinicians: due to its control of every single process in our bodies, it is very difficult
to remove meaningful parts of tissue without removing meaningful functionality from the
human being. This limits the reach of surgery, radiotherapy and multiple biopsies, some of
the most efficacious tools at the oncologists’ disposal today. Furthermore, the brain sits
flush within a fixed volume cavity – the skull – and so the swelling that is the by-product
of carcinogenosis is frequently the primary cause of death in brain tumour patients as
inter-cranial pressure builds relentlessly. Finally, clinicians treating the brain face
a unique impediment in something called the blood brain barrier: a natural and virtually
impenetrable biological coat of armour which protects brain cells from infections circulating
in the body. If we didn’t have such protection then a simple cold could easily end our life.
However, when placed in the context of cancer, this protective coat of armour makes it difficult
to get chemotherapy into the brain. These three aspects of neurology make clinical practice
in the field of neuro-oncology the most severely challenging of any in oncology today. Compared
to other cancers, brain cancer has a very low profile, and yet it claims more young
lives than any other cancer. Nobody survives it’s most aggressive and lethal form, glioblastoma
multiforme, referred to in medical circles as ‘the terminator’. Part of this is because
of the difficulty we just described in treating the brain. But brain cancer itself is differentiated
from more common cancers by it’s cellular heterogeneity: this means it’s highly differentiated
cell populations are inherently complex and varied, and so simple targeted treatments
affecting only some areas can not impact it’s overall ability to mutate and proliferate.
A complex problem calls for a complex solution, and biological heterogeneity demands therapeutic
heterogeneity: or more simply brain cancer is telling us that each patient is has a different
disease, and that they need a different cure. This genetic instability is the hallmark of
all cancers. In this sense, cancer is the most terrestrial of diseases, starting as
a simple malfunction of a living organism, it demonstrates the same remarkable capacity
for adaptation and change, that has defined of all the great survivors of evolution. It
is this ability to modify it’s DNA structure from generation to generation that results
in the phenomenon referred to as drug resistance – the principal barrier to treating cancer.
All of these facts, the limitations of traditional intervention methods when dealing with the
brain, cancer’s most sinister characteristics, and then additional problems specific to brain
cancer, are acknowledged and agreed upon by every hospital and every expert in the world.
The tragedy for brain cancer patients today is that the care they will receive does not
come close to reflecting the scientific knowledge now at our disposal. This is where the problems
facing brain cancer, if they could be solved today, could revolutionise the treatment of
all cancers tomorrow. ‘A round trip to Hades’ in southern California an academic
and scientist has dedicated his life to pursuing better outcomes for brain tumour patients
since being diagnosed himself in 1995 with the most aggressive type of brain cancer,
glioblastoma multiforme. Given only a few months life expectancy, Professor Emeritus
Ben Williams was an extraordinary patient, and now nearly two decades later, he is an
extraordinary survivor for patients, his book Surviving Terminal Cancer is a source of frank
assessment and logical analysis of all available treatment options, often lacking from their
own medical team. Every year, Ben updates this invaluable source of information making
it freely available to any patient surfing the internet via a national brain tumour charity.
His remarkable journey has taken him from moribund patient, to highly respected survivor
and patient advocate. When I was diagnosed with brain
cancer I knew almost nothing about the disease other than that it is one of the worst medical
diagnosis you can get. My first reaction when I heard of that was to basically have a shiver
down my spine because I knew I probably didn’t have much chance of surviving. I hadn’t even
heard of a glioblastoma at that point. I was told that it was the worst kind of tumour
you could have and that nobody survived it. For the first couple of weeks after that I
was just in shock. I mean there was no other way to describe it. Ben was told he could expect to live
for 12-18 months if he was lucky, and that the chemotherapy treatment available to him
would not save his life. For the first several months, most
of my thinking was, you know well, I’m going to die. How am I going to deal with it? And
I thought a lot about death. The treatment was just sort of something I was just following
along because I didn’t know any better at that point. There were no options that were
presented to me. What you are faced with is well, I don’t really have a choice. This is
going to kill me and I better try and figure out how to make that as easy a process as
possible. Like all patients Ben was prescribed
the standard of care: immediate surgery, followed by intensive radiation and chemotherapy. When you receive a diagnosis that
every one tells you is terminal – that no one survives it – it’s impossible not to become
depressed by that information. I mean I look at pictures from that period of time and I
mean, clearly I was depressed and it wasn’t until I began doing research that said there
was a possibility, that there are things you can do that would be helpful and I began to
think – well this is worth at least making the fight. And the more information I began
to find, the less depressed I became, and the more optimistic that things were not nearly
as terrible as everyone was telling me. However, before the era of the internet,
Ben’s task of educating himself quickly was considerable. The first couple of months I basically
did nothing else but reading. It was a crash course. I knew I didn’t really have much time
to do a comprehensive education so I was really trying to find a shorthand account of what
I was dealing with. Unfortunately most of the articles were every bit as discouraging
as what I had been told initially as they almost all began with an introduction that
said glioblastoma is universally fatal. But, the more research I did, the more leads that
I came across about things that had been ignored and things that – at some early stage data
from clinical trials that really hadn’t gotten much attention but still looked quite promising
and – it seemed like it was totally sensible to try and add those things into whatever
else I was being prescribed to do. So I found, you know, several different drugs that had
good evidence from medical literature of benefitting people with cancer – some of them specifically
with brain cancer but others with cancer in general. I mean things like (*immune stimulants*)
and things that were used widely else where so that I found one mushroom extract that
was used in Japan routinely in almost all cancer treatment protocols and yet it is never
mentioned in the United States. It has zero toxicity. Why would you not use it? I mean
millions of people in Japan use it. That’s a big mystery to me. How you can just disregard
something that has credible evidence. But Ben’s line of thinking was met
with surprising opposition. My neuro-oncologist raised the question
– well you don’t want to add these things because, you know, they have a lot of toxicity
and I thought, well not from what I know about them compared to what you’re about to give
me. And it turned out that while I had some side effects of some of the things they were
really nothing of major consequence so I was right about the idea that they were worth
trying. With a PHD from Harvard and a chair
as Professor of experimental psychology at the University of California, Ben had the
courage of his convictions, a critical tool the vast majority of patients lack. I realised fairly early that medical
practice is standardised for everyone and pays almost no regard for the individual variability
of patients. When I first asked my oncologist – my neuro-oncologist – if I could add the
first agent that I used – it was high dosage Tamoxifen – to what he was offering in terms
of a chemotherapy program. He just out right refused. He was unwilling to bend and we had
a major altercation over the phone and it ended up with him basically saying that we
couldn’t work together and so whether he fired me or I fired him, I was without a neuro-oncologist
at that time. But fortunately my neurosurgeon intervened and convinced my neuro-oncologist
that maybe they should let me do a little bit more in terms of participating in my own
treatment program than they would ordinarily do. Eventually we got along quite well but
I never did really tell him everything I was doing after that. Going against the advice
of my doctors was really initially an act of desperation. I mean, I wasn’t concerned
about offending them, I was concerned about staying alive and so I was going to use anything
I could get my hands on, and if that made them angry, well that was too bad. At one
point I was going down to Mexico, to Tijuana, to obtain a drug normally used for acne which
also had been shown to have some treatment benefits for glioblastomas. I had to go to
Mexico because the drug required a prescription and I knew it was going to be a great difficulty
obtaining it here so I was taking that all along without the knowledge of my neuro-oncologist.
The irony was that when I eventually told my neuro-oncologist what I had done, he said
to me ‘that was a very nice study that MD Anderson did’ – he knew about it all along,
but it was not a part of the standard treatment and so he’d never even mentioned the possibility.
In most cancer treatment protocols there is a standard treatment that the oncology community
has agreed upon and they don’t deviate from it except in the context of clinical trials.
That realisation, the beginning of my deep anger about how the medical system was working
– It made absolutely no sense to me not to use everything that might have a benefit as
long as the toxicities were acceptable. Why wouldn’t anyone want to add them? It seemed
to me totally irrational that people didn’t use everything that was available. With this strategy Ben constructed
a cocktail of drugs around his chemotherapy. When his MRI scans began to show his tumour
gradually reducing in size, and eventually disappearing altogether 6 months later, it
was clear that something very unusual was taking place. After my first round of chemotherapy
I did get a small amount of shrinkage in my tumour. That was a tremendous weight that
was lifted off of me. I mean I didn’t feel of the kind of depression that I had felt
up until that time. I mean, I was ready for the battle at that point because it didn’t
seem hopeless. So I started adding even more things at that point. And then after the second
round of chemotherapy I had a lot of progression in the tumour, and then after the third round
of chemotherapy, a lot more. Then I had a clean MRI after the fourth round. And I’ve
got clean MRIs ever since. People are always raising the question – so this might have
worked for you, but maybe you were just a rare case that responded to chemotherapy’?
Did any of these other things that you added make a critical difference? The hallmark of
my case was that the chemotherapy did work for me. I mean, I had something was different
about how I was getting the chemotherapy and the things that went with it, and I had deliberately
focused on that. I mean, I though seriously about where the resistance to chemotherapy
came from and how one might overcome it. Now retired, Ben spends a great deal
of his time responding to the desperate enquiries of patients who have read his book, offering
impartial advice whilst never advocating specific treatments. We’ll never know for sure why I’m
still alive. Certainly I did things that were unusual, but, you know, I might have done
things that were unusual in terms of the characteristics of my tumour. I don’t think that’s an argument
I take seriously now because I have advised a lot of people over the years to adopt a
similar approach. They didn’t do exactly what I did, but they added as many things as they
could to the standard treatment – and many of them have had very good success. The irony
is that almost all oncologists agree that multiple agent approaches are going to be
necessary to actually cure anything. And so, no one really is disputing that. The question
is what goes into those cocktails and what kind of criterion of evidence that you have
to have for putting those cocktails together. To this day Ben still self-administers
a maintenance therapy: a daily cocktail of vitamins and supplements designed to try and
create as hostile an environment as possible for cancer to face in his body. 18:36Logic Dictates On the east coast of America, an
advocate of combination therapies is Dr Raymond Chang. Pioneering the integration of oriental
and western medicine, his book Beyond the Magic Bullet poses an uncomfortable question
for the oncology community. RC: Oncology thinking somewhat followed
infectious disease treatment thinking because the first original breakthrough in achieving
a cure for any disease came in the infectious disease field whereas possible with the discovery
of penicillin and so fourth. Single antibiotics, single chemical moieties were able to eradicate
– cure, literally – serious medical conditions like tuberculosis, like syphilis. That was
then applied to cancer with the same logic behind it well if we find the right chemical,
maybe we can eradicate cancer just like we can eradicate tuberculosis and then that mode
of thinking dominated oncologic therapy for over a century at least. We think that most
diseases, if you simply find the right key, you should be opening the door, and the reason
why the door remains locked – the cure remains locked – is because we don’t have the right
key. So we should keep looking for new keys or try to improve the key that we have and
we will eventually open the door. What if this door has multiple locks? When you keep
looking for one key, it’s not going to open the door no matter how hard you look. It will
never, it will fail, the whole strategy of research will fail! Then maybe the way of
thinking is wrong. It’s not that we need better drugs, but we need to know better how to deploy
what we have already. If we have ‘cure’ or ‘control’ already in our hands except that
we’re not using things properly. As proved to be the case with childhood
Leukaemia and aids, it was the combination of existing treatments that delivered the
breakthrough. Today infectious disease treatments follow this logic. RC: Hepatitis C, hepatitis B – chronic
viral infection – HIV obviously. They are all attacked with multi multi agent, multi
target approaches – and with success. Cancer treatments are kind of behind again. So hopefully
it will follow the lead of the infectious disease practitioners. The idea of a cocktail approach to
cancer treatment has gained adherence amongst the oncology community. HF: I think that if we are going to
try to treat this disease we need to be using combination therapy from the get go. Single
agent therapy is not likely to be very affective with a disease with so many molecular perturbations
underlying its ability to be invasive and resistant to therapy. AE: What you want to design for a problem
like cancer is not a drug or an intervention. You want to design a solution – because that’s
what patients want. So it’s a lot like your computer: there’s amazing components in there
like your microprocessor or your hard drive, but individually they aren’t worth anything
to you until they are put together into an interoperable system that becomes your laptop
that’ll do word processing or send emails Now that’s of value to you. Today in drug
development and in clinical research we need to be thinking of those kinds of integrated,
interoperable solutions. AP: With glioblastoma we’re really climbing
a mountain. Every therapy that we see a modest success for gets us a little bit further up
the mountain then we set up a new base camp, and then we come up with a another therapy
that gets us further up the mountain, set up a new base camp. The concept of synergy
is really important here because what if we could just get further, faster? An example of why it is that combining
different treatments together is in fact the development of what is now the standard of
care: It used to be that you used to receive radiation first and then wait a month or so,
and then start on your chemotherapy. The new protocol is that you have the radiation and
the chemotherapy together. It has produced a better outcome. Clearly the change of putting
them together simultaneously as opposed to sequentially was a step in the right direction. RC: Current management of brain cancer
as well as many other cancer conditions involves a multi disciplinary approach where surgery
is deployed, radiation is deployed, chemotherapy is deployed, and targeted therapies are deployed.
So one can argue that it is already, in a way, it’s already mixed or cocktails and not
just one single therapy But, much more can be done. Many other drugs can be used without
much toxicity without much even cost. Simple, simple drugs. Although there is general consensus
of the advantages of the cocktail approach, there is disagreement about how much information
is needed to start combining untested treatments together. How far and how fast this can be
taken for individual patients is the fundamental issue. The big problem with cancer treatment
is that the tumour develops resistance. I mean, you know, so it’s usually that the treatment
is only partially effective in the beginning – at best – and what you then get in an evolution
of resistant strains of the tumour, and so the more you treat it, the more resistant
it gets just through the process of evolution. The biggest risk in all of this is you’re
going to be dead very quickly from your tumour unless you do something other than what is
being offered from the conventional medical treatment. AE: We always balance the potential
gain with the potential toxicity of an agent and making a decision whether to include it
and if so, how to include it and when to include it but we’re not treat colds, we’re treating
glioblastoma and what risks you might take with a cold are going to be far less than
the risks you are willing to take with someone with a glioblastoma when you know the natural
outcome is so dire. It is clear that cocktail therapy
represents an excursion into the unknown, with corresponding uncertainties about the
risks involved. 25:33: MH: Some of these cocktails involving
10 or more substances can have life threatening complications and for the safety of the patient
it would be much better if the physician knew about it and could appropriately follow. There
can be some aggressive attitude of some physician starts experimental treatments especially
with free purpose, non approved drug cocktails. And I can very well understand that patients
may try to avoid this conflict with a treating physician and I think that the solution is
on the side lies on the side of the physician. 26:13Resistance the reality facing the vast majority
of patients, is that their doctor will not engage with any experimental therapy outside
of a clinical trial, even in the context of a terminal diagnosis. We wanted to try and
understand the reasons behind this seemingly unnecessary resistance. RC: Realistically there are other practices
beyond medicine. It has to do with capitalism, it has to do with health care structures,
systems and so fourth. Mono therapy is easier to carry out. If something goes wrong, it
is clear what’s wrong because you’re giving one treatment at a time so if the patient
has a server side effect it’s that treatment – it’s that drug. Regulatory wise, it’s very
difficult to get studies going involving multiple agents, because let’s say if you’ve got five
agents – instead of testing one thing at a time then you have to test A against B plus
C plus D plus E or, A plus B against C plus D plus E. There are then, to the power of
five, so many different variations possible. That means you have to do so many studies.
Practically it’s almost impossible to study these things if it becomes complex. So a simple
monotherapy approach is easier, cleaner for management purposes – but it may not be as
effective. It is unconscious because doctors don’t necessarily think about it, but they
implement it in this fashion. This is the way how studies are done. You don’t put patients
on three new X, Y, Z unknown new treatments at the same time because the issue always
comes up that well, if it works, what did it? Then we don’t know. That is not acceptable
to science. You have to be careful that the doctors need to be scientific but when you’re
treating the patient, is it for science or is it for the patient? Sometimes we forget. Other obvious candidates for cocktails
are natural compounds. These naturally occurring substances cannot be protected by patent and
so no one company can gain a monopoly over their supply. Totally non-toxic, and with
years of data to prove its efficacy in cancer care, curcumin should be an obvious adjuvant
for any cancer protocol, and yet it is rarely used in western medicine. We travelled to
the world’s largest specialist cancer hospital, MD Anderson in Houston, where the series of
laboratories dedicated to natural compounds are testament to the holistic vision behind
the Texan project. BA: As of today there have been over
150 clinical trials that have been completed. And the answer is yes it works and it down
modulates bio-markers. You know, there are only 20-25 driver genes, and that I have taken
all those driver genes and asked ‘are they down modulated by curcumin?’ Because that
is what the drug industry is targeting and the answer is yes: curcumin alone, has over
ninety different targets, ninety different targets, it is not just a mono-targeted. So
this is what the drug industry calls a ‘dirty drug’. Any drug that hits more than one target
is a dirty drug for them, they don’t like it. There are only two rules of the game that
I have learnt from my days in Genentech (and there is no third that I know of) .. Safety:
number one, whatever you’re giving to the patients should be absolutely safe, it shouldn’t
hurt them in any way. Second is the efficacy. There is no third rule, and curcumin meets
both of them. But as any cancer patient will testify,
there is huge opposition from the medical establishment, towards adding natural compounds
to traditional cancer treatments. The reason most patients are given, is that it ‘may interfere
with your treatment’ although only in rare cases is there any evidence to support this
claim. AB: In medicine today, there is a buzz
word and that is called ‘targeted therapies’. Targeted therapy means you pick a single gene,
a single protein, and you try to find an inhibiter. That is what they call a ‘magic bullet’. They
have come up with a lot of magic bullets. Only thing is, these are not bullets and these
are not magic, so there is a lot of frustration, asking where did we go wrong? Where they did
go wrong was thinking that cancer is a single gene or single protein – a single target disease.
By now, we are living in the era of ‘omics’: genomics, proteomics, metabolomics, and all
of that is out there to tell you that cancer is a multi-genic disease. No matter which
direction I look at, people’s mind is set, and their mind is set on targeted therapies.
They want a targeted therapy, if it is not targeted they are not interested, period.
It doesn’t matter whether it does anything good for the cancer or not, they are not interested
and that’s where I face the biggest resistance. I have people tell me point blank in my face,
right here in MD Anderson. They say, ‘well Dr Aggarwal, anything you do with respect
to natural products I don’t believe even one bit of it. They don’t even want to read and
we publish in the same journals. We are most highly cited. People don’t want to read. There’s
this, you know, in born bias. My problem with the ethics of oncologists
is that they want to pre-empt the decision and they don’t their patients have any leeway
in making a decision that sort of kind of moves them in the direction of alternative
medicine. It’s a real concern on their part. I mean, professional reputations can quickly
be ruined if you’re viewed as one of those kooky guys who goes around trying to throw
out anything under the sun into your treatment protocol. History is littered with scientific
breakthroughs that were castigated for their implications for the prevailing status quo.
When Copernicus introduced his heliocentric theory to the world, the shock to the belief
system reverberated for centuries afterwards: Gallileo Gallilei was persecuted for his acknowledgement
of Copernicus’ theory and his pursuit of a new rational science in its wake. Even Gallileo’s
presentation of his new invention, the telescope and it’s irrefutable new evidence, could not
dampen the fervour of his condemnation. In the nineteenth century, Ignaz Semmelweis,
a relatively unknown doctor, a Hungarian practising in the venerated hospitals of Vienna at its
empirical peek, noticed an alarming correlation between the new practice of pathology, and
the advent of a series of deaths of both mothers and babies in the maternity wards of those
same hospitals. His suggestion that perhaps his fellow surgeons should consider using
chlorine to wash hands before operating on patients, was met with vicious resistance.
Unable to substantiate his theory scientifically, Semmelweis was ostracised professionally by
his peers for daring to question the status quo. He died 15 years later in a mental institution,
a broken man, yet a century and a half later he is venerated as a national hero in Hungary,
where statues and coins carry his legacy as the father of sterile medicine. Today, the
Semmelweis reflex is a term used to describe an illogical and exaggerated response to a
challenge to the prevailing dogma. Unfortunately – the Semmelweis reflex is alive and well
in today’s medical establishment: Barry Marshall, a little known doctor from Western Australia,
had identified a bacteria in the early 1980s that indicated stomach ulcers were caused
by bacteria. This was heresy to the established thinking in the field of endoscopy, which
was convinced that stomach ulcers were caused by stress. As a result Marshall’s thesis was
not published in any medical journals and sat on the shelves gathering dust while hundreds
of thousands of patients across the world had their stomachs removed, unnecessarily
so according to his theory. With the bacteria in question only able to develop in primates,
but with testing on primates prohibited, the successful animal experiments that the medical
establishment deemed pre-requisite for Marshall to progress to human trials, could thus never
be completed. So locked out of both animal and human experimentation, but convinced of
his theory, Marshall chose to experiment on the one human he did have legal access to:
himself. In front of an audience of stunned peers, he downed a petri dish full of bacteria
grafted from a patients’ stomach, and claimed to have infected himself with a stomach ulcer.
The proof duly came, as did his cure without the need to remove his stomach, swiftly followed
by an avalanche of awards and praise from the establishment, culminating with the Nobel
Prize in 2005. Beyond the more obscure issue of medical hegemony, lie more obvious reasons
for why combination therapies do not reach patients. AP: If you have: a drug A from company
A, and a drug B from company B, and a drug C from company C, it is extremely difficult
to get all three of those drug companies together to agree to use their drugs to treat a particular
disease process. It’s much easier if the drugs all come from one company and that is a fundamental
challenge that not just neurosurgical patients with glioblastoma face, but all cancer patients
face. And from the company stand point one could make a good argument that it’s reasonable
and understandable that this is the case because they invest hundreds of millions, sometimes
billions of dollars to develop that drug, and as that drug comes to market it goes to
the FDA, the application of that drug to other disease processes in combination with other
drugs could cause a lot of problems for them. So it’s a very difficult thing to address. On top of the reluctance of western
medicine to consider natural products as they cannot be patented, for the very same reason,
drugs whose patent has expired are similarly discarded as they cannot guarantee a return
on the investment required to run a clinical trial. This results in a large number of drugs
with strong laboratory evidence for anticancer properties never getting anywhere near patients.
In some cases, even when human trials have been run it is still not enough to bring the
drug into the mainstream treatment. RC: A very nice example is the use of
the old malaria drug which is dirt cheap, Chloroquine, for brain cancer where nice trials
have been carried out showing improvements up to 50% survival time when it’s added to
standard chemotherapy. It has almost no side effects. It’s one pill a day. It does not
mean the patient has to suffer going to the hospital, get a drip, any of this. It’s dirt
cheap. Why not? Well, FDA has not approved its use for this condition – for one. The
information is not widely disseminated. There’s no big drug company behind the manufacture
of chloroquine to market it for this use. Nobody makes much money if suddenly every
brain cancer patient starting taking chloroquine, it adds very little to the bottom line of
any particular business or company. JB: So it is more and more important
for us to look at these drugs that have been left on the shelf, that big pharma wants nothing
to do with, but we don’t initially have the time or the resources to provide the data
managers, the IRB fees and start up fees that it takes run a good clinical trial. Aside from the influence of the medical
world status quo, and the economic reasons hampering development of combination therapies
for cancer, there is a strong feeling amongst the patients we interviewed as to why oncologists
are unwilling to deviate from established best practices, even in the context of terminal
disease. AP: One of the problems from a patient’s
perspective is that they want as many drugs as possible to facilitate long tern survival,
and that’s a very reasonable request from the stand point of a patient. If you have
cancer, you hear a certain drug might be effective in your particular type of cancer, you want
to access that drug. You hear that another type of drug might be effective, you want
to actually just go ahead and combine those drugs, and so fourth and so on. From a patient’s
perspective, you are entitled to pursue any type of therapy you want to. From a provider’s
perspective, from a neurosurgeon, a scientist, from a a neurosurgical oncologist’s perspective,
we have to be very, very careful about what we recommend to patients in terms of going
after therapies that are unproven. RC: Doctors are judged by so-called
standards of practice in the community. So, if in California this is the way we do things,
here, in LA, this is the was we do things and you do it differently and the patient
gets hurt, and you’re in court, they will summon your peers and say well, how do you
do things usually? And everybody says ‘I only use Temodar, I don’t do Temodar + chloroquine This issue of liability is one of
the silent enemies in the war on cancer. Drs and hospitals who would willingly take more
risks for their patients who have run out of options, are discouraged from doing so
by fear of malpractices suits. This fear of prosecution is not limited to doctors, but
runs deep through the entire system, dissuading individuals and teams from doing anything
outside of the box for their patients. RC: The specialists are at major cancer
institutions that does not treat patients as individual unlike what patients may think.
They treat as a group. They can call it a team approach, but they treat by committee,
literally there is a committee of doctors who review cases – it’s called a tumour board
– and almost, you can imagine, 6,7 specialists at the centre every week, sit down and go
over new cases and decide ‘this is what we’re going to do.’ Now, that also creates an issue
because then everybody has to agree for one, then of course what everybody agrees on in
any bureaucratic structure has to be the lowest common denominator. Okay? But that’s the safest
way for the doctors and the hospital because if there was a problem, and if the was a charge,
they say well, ‘six specialists had a committee meeting on the same week – and we all agreed
you want to sue six of us? And we represent the hospital are you going to sue the whole
hospital for this decision? every one of our patients get exactly the same thing. What’s
wrong with this? We are following the guide lines from the American cancer society’. So,
everything is therefore protected, protected, protected for liability reasons. So it’s fool
proof. If you try to be individualistic, stick your neck out, give chloroquine because there’s
a paper that says give chloroquine, and something goes wrong, you don’t have anything backing
you up in the court of law. It’s much safer to follow a protocol. A protocol is one thing
at a time until it’s proven otherwise. The proof may never come because there is no funding
to try to prove these things. Who gains from proving them? Who is going to fund the proving
of this? These are much larger issues that I think will hamper developments of true cocktails
unless there is radical changes in health care systems and social systems. It may not
come. 43:23Lightening doesn’t strike twice Ben’s Williams book is nothing more
than a blueprint for anyone who wants to follow a more pro-active approach to their own treatment.
One such patient was Richard Gerber, a fellow American academic living in Italy, who was
diagnosed with the same lethal brain tumour a decade after Ben. Given just months to live,
Rich had nothing to lose. During the chemotherapy and radiotherapy
that I had – although it was very exhausting – I started reading at night, articles and
journals, and I realised that therapy was not going to really make my life any longer
so I started doing research into alternatives, and little by little, on the internet, I came
across this name ‘Ben Williams’ who had written a book. I ordered the book. And it basically
is teaching people to take their matters into their own hands and to be their own doctors
in part. So far, this cocktail approach that he writes about in his book has proved efficacious
for me. I wasn’t just blindly following Ben. In fact, I wouldn’t have followed Ben at all
if his arguments weren’t logically convincing. in common with Ben, Rich shared a
scientific background, he is an expert at developing solutions for complex problems. I took what we call a ‘black box’
concept that is glioblastoma is a very, very complicated phenomenon. Nobody knows: how
it works, how it grows, how it gets started, how the therapy works, and papers are published
on very specific subjects and very specific genetic paths ways, but there is no integration
of this information. So, my approach was based on finding as many agents which could block
assorted path ways which activate glioblastoma, and doing it all at once so that the glioblastoma
would have less of a chance to mutate and escape via a path way because I would already
be blocking that pathway. of course, assembling and consuming
an unsupervised and untested cocktail of drugs and neutraceuticals is daunting even for someone
with an in depth appreciation of their disease. One of the patients we interviewed equated
it to playing Russian roulette whilst on death row. My doctor was a very sympathetic
oncologist, but she was very ‘by the book’. She didn’t want me to do anything else. Coming
up with my own notions I suggested to this doctor that I would like to take melatonin.
I tossed this out as sort of a test because at the time I was actually taking 10 or 15
other pharmaceuticals but I thought I would start small and she didn’t want to hear about
it. She told me not to take melatonin, that it would just confuse the matter. At that
point I realised that I was on my own because if I couldn’t confess to my doctor that I
was taking melatonin, how could I confess to her that I was taking chloroquine, Celebrex
and other pharmaceuticals. I didn’t add all the ingredients at once. I added them incrementally.
I basically included any ingredient, be it a supplement or a pharmaceutical that was
active against cancer and didn’t interfere with the other ingredients. The pharmaceuticals
had to be dosed correctly, and the dosage I used was that carried out in the research
paper on cancer that I found. You have to read very closely these articles to get the
correct dosage – but it’s there. At its peak his cocktail numbered
over 25 different components, and in order to access them all, Rich broke every rule
in the book: From feigning symptoms of other ailments in order to access non-cancer drugs
that he believed may also act against his disease, to forging prescriptions. There were moments during my cocktail
therapy when I thought I was doing too much, and I was getting out of my own comfort zone
which is nothing like medicine, but, I realised that the alternatives were very small: either
I tried something much more radical than the standard of care, or I would die. And when
you’re faced with that kind of decision, why not use more ingredients? Long term survivors of malignant
brain tumours are extremely rare. What makes Ben and Rich even more unusual amongst this
tiny data group, is that they have never had a recurrence – their cancer has never come
back. A glioblastoma can’t really be cured.
Never. I never think about cure and I don’t talk to anybody about cure. I think that every
year that you live without a recurrence is great. I think Ben Williams now has lived
eighteen years without a recurrence if I’m not mistaken. I’ve lived six and a half years
without a recurrence. At that point you can say that we’re under control, but you can’t
say that we’re cured because there is always a possibility that it could come back. 49:33Ethics in question After the horrors of the human experimentation
that characterised the holocaust, at the Nuremberg trials the international community laid down
the founding principals of a clinicians ethical obligation, initially referred to as the Nuremberg
code and later ratified in the Declaration of Geneva as an extension of the Hippocratic
Oath. Building upon these foundations, the world of medicine unilaterally subscribed
to the Declaration of Helsinki in 1964, and its primary revision in 1975 that introduced
the principal of ethical review by an independent committee. In doing so, the global medical
community enshrined the moral truth that ‘concern for the interests of the subject must always
prevail over the interests of science and society’. Can we honestly say that today’s
double-blind studies on terminal cancer patients adhere to this principal? Frankly, that I don’t know how a
neuro-oncologist could go home and look them self in the mirror at night given what he
knows and the outcome of his patients are. I just don’t think it’s even ethical. I wouldn’t
be able to live just presiding over patients, just giving them radiation and chemotherapy
and at the same time, knowing that they are all going to die. HF: I think the general concern in the
oncology community is that this is a terminal disease and when diagnosed with a GBM you
are going to die. I think that philosophy is kind of counter productive to doing anything
meaningful, so I think our goal is to put patients on clinical trials to press the field
forward, but when you can’t do that, to do something better than a standard of care which
is palliative. MH: What we are fighting against is
the negligence that physicians are not aiming to inform themselves, that they are not forming
an opinion themselves. HF: If you face this disease and say
from the get go that this it is incurable – you will always be right, all your patients
will die and you have no business treating those patients in the first place. I think it is one of the toughest
situations in everyday clinical work. This is a point were it is really necessary to
really explore the patient’s wishes and really find out if the patient is willing to take
an additional risk for a chance, for a possibility of having a better cause. The problem is that
a patient who is asked to take an additional risk for a chance to survive will almost always
say yes. So the central issue is the question
of protecting patients rights at both ends of the spectrum: whilst uninformed vulnerable
patients need protection from unreasonable offers of experimental therapy at one end,
equally should patients at the opposite end of the spectrum, who do not wish to accept
a palliative standard of care, be denied the right to fight for their lives? When their
doctors refuse to co-operate, these patients inevitably find themselves outside of the
medical system. We wondered how many other cancer patients have embarked into unchartered
territory of self-medication, without their story ever coming to light. In California,
we heard of another desperate struggle against terminal cancer. But for Neil and Margo Hutchison,
there was no happy ending. neuroblastoma, a rare cancer of the nervous system, claimed
the life of their eldest son Sam aged just 8 years old. MargoH: He was a very active little
kid. Loved sports, loved anything with balls, loved trucks, he ran like the wind, we was
a funny, great fantastic kid. When he was four and a half we were at a soccer game and
he sat down and said ‘my legs hurt’, and he always used to jump out of our van and he
started to sit down to get out of our van so we that something was definitely wrong.
We decided to get some blood tests and an X-ray and he was diagnosed with neuroblastoma. Sam began one of heaviest chemotherapy
regimens used in medicine with accompanying stem cell transplant that meant he lost his
hearing and would be sterile for the rest of his life. But with such a high grade of
malignancy Neil and Margo were told Sam had very little chance of surviving. NH: Well first off, I mean, you’re shocked,
I mean, I think even parents of someone diagnosed with paediatric leukaemia would just, you
know, – it has a very high survival rate – you know, it still it punches you in the gut,
but when they sit you down MargoH: You’re just yeah, you’re in
shock for months. After the shock dissipates, the dislocation
between the patient’s perspective and that of their medical teams was a common factor
in all the cases we covered during filming. It is clear that while the Hutchison’s have
both a deep respect and appreciation for the doctors who treated their son, they had also
come up against the same compassionate fatalism that proved so unpalatable to Ben Williams
and Richard Gerber. NH: I think that one argument that we
used to have with doctors when we talked about issues like this is, they’d say I’d say like
‘hey listen, throw the book at these kids, it’s non toxic, get them in there, throw cocktails
at them and see how they do.’ Their argument back to me would be like well, ‘if some child
survives we don’t know why’, and I’d say ‘yeah, but that’s a medical, scientific perspective.
From a parent perspective we don’t care why. He’s alive and we’ll figure it out’. If we
keep doing it we’ll figure it out. We’ll back door the answer. Somehow, someway, some shape
or form. The scientific community wants to know why. MargoH: They believe in what they’re
doing and, know you, they want something that’s science based. They want a clinical trial.
They want the proven results. That takes years to get that kind of data, and these kids don’t
have that kind of time. NH: And you’d see the data, you’d see
child after child die and you’d have that mental calculus going in your mind all the
time because you don’t want to harm your kid either because the Hippocratic Oath is apparent:
First do no harm. It’s not about that MargoH: Right, and so it’s not like
you’re making crazy, uneducated, you know, ‘we’re just going to try anything’ decisions
but NH: You are absolutely right but like
okay, but I know this outcome. I don’t know what this is going to be, but I know where
this is going. Given that the probability that
the patient is going to die is astronomical – it’s almost 100% – what harm is there is
adding other ingredients to the therapy? Why on earth would you possibly
oppose it? And the only answer to that is well, that’s not part of the standard care
and we’re afraid that if you use anything other than the standard of care that somehow
we’ll make things worse in a way that we don’t understand. That’s not an acceptable position
in my view. For the vast majority of patients,
it is also an unacceptable position. The advent of the internet has seen a growing underground
network of patients and carers supporting each other. This film is a direct result of
such a community. NH: We had, you know, the whole community
of neuroblastoma parents who were medical doctors and things themselves, and what we
tried to do was read the preclinical data, you know, and we were just trying to stay
ahead of the curve and kind of predict where things were going to go clinically. You know,
you see a single agent clinical trial and you know the data for that or you talk to
– it might not be published data – but because we are neuroblastoma community we know that
10 kids are on it and they all progressed. There’d be publish, preclinical data saying
that ‘hey, the next trial that’s going to come up is going to be adding this second
drug’, and so we would get the second drug, and that was very common place. High profile survivors like Ben and
Rich find themselves inundated with requests for their advice, and having experienced the
despair of falling outside the medical system themselves, they can appreciate the desperation
of patients with no where to left to turn. SS: I’m an engineer, and many engineers
carry out risk benefit analysis naturally and routinely in their work. In terms of the
cocktails that I had identified, I did my own independent research, evaluated what the
potential benefits were compared to the side effects, and it was quite clearly something
that ought to be tried. Many of the doctors feel that they are not
able to engage in these off plan treatments, and perhaps those that are outside the normal
sphere of training because they tend to feel that the Hippocratic Oath limits their ability
to do that in the principle of ‘do no harm’. But I believe that there are equally sins
of omission as there are of commission. With the benefit of hindsight and the reflection
of where I am relative to the prognosis, I am concerned that this approach could not
have taken place sooner. 58:47″Stewart Stoneman died on the
30th of November 2014″ “He never found a doctor willing to
prescribe off label drugs for his cancer” AP: There is no doubt that in the future
we’re going to be looking at multiple therapies. The question that arises: doesn’t the patient
have the right to go an pursue combination therapies and put them all together in a way
they think and their doctors hope will facilitate a long term cure? The problem again comes
back to the issue of toxicity. Unless you carefully study these combination therapies,
you may be doing more harm than good in many cases, and although that there is clearly
the impetus to move forward with combination therapies, they need to be studied. However, for the reasons outlined
in this film, there is a distinct lack of clinical trials investigating a cocktail approach
to cancer. Instead, it is normal practice to expect patients to forgo curative treatment
in the hope that their sacrifice will someday benefit someone else in their same position. RC: If you go to a major medical centre
where they are doing clinical trials, the trials are not really a hundred percent intended
for the patient, they’d be intended for a future patient, it’s intended for science
– or for a drug company – but, it’s intended to find out more about the drug, it’s not
intended to cure the patient. Patients are not aware of that. For science it is important
to study things singly because otherwise it’s confounding. We cannot deal with multiple
unknown variables. You throw five drugs that we don’t know much about t somebody and they
get better, we don’t really know what happened. Which one of A, B, C, D, E did it? We don’t
know. You want to find out how a drug works that’s in scientific spirit. That’s great
for science, but there is some conflict with clinical care which is with a different intention:
you want the patient to get better. When looked at closely, the history
of cancer tells its own story: In another era, when doctors were more empowered to pursue
patient survival as a primary objective of clinical care, dramatic progress was achieved
in a relatively short period of time. One such doctor whose belief system is entirely
geared to patient outcome was a young haematologist working at the newly formed National Cancer
Institute in the early 1960s. Emil J Freireich was certain he had figured out a way to send
leukaemia into permanent remission. But he faced enormous resistance for attempting to
combine highly toxic chemotherapy agents. EF: When I started treating leukaemia
– I have a slide of a quote from an article that was written by a guy named Arthur Haut,
who was one of the senior physicians at the number one haematology department in the world
in 1955 when I went to the cancer institute. The quote says just what you said: giving
these drugs , 6MP, methotrexate, prednisone to these children is just prolonging their
suffering, it has no effect on their survival. And he was on our consultant (panel) and he
told our advisors that Freireich should no be allowed to poison these dying children
-to let them die. Undeterred by fierce resistance from
his professional community, Freireich questionably pushed ahead with the assistance of some desperate
parents, and the rest is history. Today, a giant in the field of oncology after blazing
the trail towards cure for childhood leukaemia, and in the process inventing the platelet
transfusion, at the age of 87 Dr Emil J Freireich has half a century of outstanding achievement
in clinical practice to reflect upon. 1:EF: See I’m a devotee of the Hippocratic
Oath. That’s why it’s on my wall. Every physician in the United States, and I think in England
and in Europe, who graduates from his medical training swears by the Hippocratic Oath. Now
what’s the essence of the Hippocratic Oath? Now what’s the essence of Hippocratic Oath
is that, as a physician, I will always do whatever I can to help a person who is ill
and consults me. 1:For cancer patients staring death
in the face, the chilling realisation that despite a palliative standard of care, they
must wait for their cancer to inevitably progress before their doctors will engage with experimental
treatments, defies belief. In the vast majority of cases, only then do experimental treatment
options become available to patients. We asked Dr Freireich if in his opinion, this broke
the Hippocratic Oath 1:EF: It certainly does. Is there ever
a circumstance where a patient should be denied treatment which could – in someone’s imagination
– help him survive his disease? And the answer is no. 1:04:07System Failure 1:EF: Would the things we did in 1960
be possible in today? The answer is, unequivocally, capital ‘N’, capital ‘O’ – NO! 1:By obliging doctors to follow rigid
protocols, our system for validating cancer treatments is not only failing patients, but
it is also failing the innovators who are developing treatments: a hidden consequence
of forcing patients to wait for cancer to reoccur before giving them access to experimental
treatments, is that potentially promising treatments are first tested only on these
‘recurrent’ patient populations, who already have genetically mature cancer, and thus are
far less likely to respond to the drug or treatment than an early stage patient. This
means potentially life-extending treatments for the newly diagnosed are discarded forever
because they cannot show effect first on moribund patients. 1:EF: reforming regulations is the most
important thing we can do in advancing health in the world. The AIDS patients told us how
to solve societal problems for specific diseases. See, the AIDS guys were homosexuals and they
were used to being politically active and they were organised, and when the FDA said
you have to do a randomised trial where you get treatment you know won’t work and compare
it to treatment you think will work they said ‘hell no!’ and they marched on the hill and
they won. My personal view is that that’s the way medical problems should be solved.
First we need the knowledge, then we need the social solution. 1:ACT UP – the AIDS coalition to
unleash power – was a direct action group widely credited with instigating the rapid
acceleration of AIDS research that transformed the once deadly virus to a chronic condition
in little over a decade. Larry Kramer, New York City playwright and author was a founding
member, speaking in the late 1980s as the AIDS pandemic gripped the world in the face
of institutional and political indifference, his words echo violently in the ears of cancer
patients today: ‘placebo studies were not designed with terminal illness in mind’ he
said and the ‘academic mechanism of testing drugs is becoming life-threatening rather
than life-saving’, it’s ‘genocide by neglect’ he claimed. As a result of ACT UP’s unprecedented
lobbying of congress and the FDA, which included emptying urns onto the white house lawn as
per the will of their members’, today’s life saving treatment for AIDS is given to patient’s
despite it never having passed a randomised phase three clinical trial: How many cancer
patients must die before the regulators recognise this needs to be adapted to oncology in the
same fashion? 1:EF: All they have to learn to do is
balance benefits against risks. If you have nine drugs that are going to cure glioblastoma
and you have a patient that is 100% likely to die lets give them the nine drugs! Who’s
against that? You can’t do anything risk free. That does not exist. You can’t walk across
the street without taking a chance. You can’t wake up in the morning, you can’t eat food.
I mean, it’s nice to do as well as you can, but you can’t be insane and we are insane
now. The regulatory process is insane. They are trying to protect people. They inadvertently
get into a situation where they kill people but that’s not their intent. We’re just human
unfortunately. 1:For patients and carers, once these
inefficiencies come into focus, the incentive to adhere to the rules of clinical trials
evaporates along with the validity of the precious data the trial produces. 1:NH: Do you want me to be totally honest?
Yeah, sure, neuroblastoma patients ship drugs. We’d ship drugs by fed ex. We’d find clinical
trials and we’d be on a single agent and we’d – other parents on the other trial would send
us their drugs and we’d send our drugs. We had viruses from Israel that other parents
had given us that we’d tried and that’s what we did. There’s a whole black market and grey
market of drugs because parents are so knowledgeable. I mean, there’s Doctors, PHDs, MDs that have
children with neuroblastoma and it’s a very tight community and they would do anything
for anybody. In fact, we, you know – that’s what we did – created our own clinical trials
for the most part. 1:In randomised phase 3 trials, you
have the additional disincentive of placebo control for half the patients. A quick glance
at the appalling enrolment rates around the world and we can see that patient’s vote with
their feet. 1:EF: It’s so obvious that if the FDA
allowed us to be rational about treating cancer patients, we could move them all one hundred
times faster. As we did with AIDS, because what happened was, the drug was good and the
patients didn’t have to die to prove it. And as you said in the beginning ‘you need to
do a randomised phase 3 clinical trial’ No! if you have phase two evidence that’s clear,
if you have an objective response, objective survival, objective progression free survival,
that’s it The truth is in itself. You don’t have to do comparison, you have to have the
truth, you have to have reproducibility, you have to have a lack of bias, and what you’ve
got there that’s the answer man! The AIDS guys did it. The cancer patients have to do
it. We have to force congress to change legislation so that when a doctor and a patient agree
that the benefits succeed the potential risk that should go. Whatever way we make it, that’s
got to go. 1:10:17New horizons 1:In all of the clinical trials
to date, there really hasn’t been much progress. Meanwhile, those people however are dying.
Yes, people live a little bit longer with the standard approach that we have now, but
it’s not much. And so, I would say this approach is not working. It’s time to try something
else. 1:AE: Traditionally, regulatory bodies
have made decisions that have been based on population studies. So if you think about
it for a moment We introduce a drug into a large population in which we know there are
many variables in that population – people are different – and we can’t control for those
variables, we don’t know what they are sometimes, we just know they exist. So the way we dealt
with that in the past was to create this statistical model of randomisation and, in fact, blinded
randomisation so we cover our eyes, and we flip a coin, and we divide people up, and
we look for an outcome, and when we get an outcome we put a statistical number on it,
and that gives us some assurance that yes, that was really due to the drug and not something
else. Do we need that today? If I could go into that population and I could – today – tell
you about those variables – which I couldn’t before – because now I understand those genetic,
molecular make up of their individual cancer, and I also under stand their genetic molecular
make up of them, as a person, and now I can refine those populations. Do I still need
to put a blindfold on and flip a coin? Or can I begin to be much more rational about
who I would treat with a particular drug and who I would not. That is the adaptive trial
design. That is what cancer is teaching us and telling us what we can now do, so we don’t
need to depend upon that old model. We can be much more sophisticated, much more rational,
and we will get answers faster, we’ll be much more certain that our answer is in fact correct,
and we will be able to allow patients to have access to lifesaving drugs quicker, faster,
and with more assurance that they are going to help them and not hurt them. 1:We accompanied Ben to University
of California Moore’s Cancer Centre to meet one of a new generation of oncologists engaged
in an ambitious program of personalized medicine… 1:SK: There’s two issues. One is, you
know, what are the best combinations for each particular patient? Because, I think we all
know that glioblastoma is a different disease in every single patient. If you took a hundred
people in a room there’s probably fifty diseases, and so what we’re finding is that single drugs
seem to work better in some patients than others because of the genetic make-up of the
tumour, and so when you talk about combinations it’s even more complicated. But we actually
have a project where we’re taking all the genetic information from each patient, putting
it into a computer, and coming up with an answer to what drugs would be most effective
to each patient. So, it’s really a personalised medicine approach to understanding the genetics
and using that information to find the best combinations. 1:So as we move towards personalised
medicine where patients will receive combinations of treatments, and that these combinations
should reflect the genetic characteristics of different patients, then the only logical
conclusion to be drawn is that until we dismantle the sanctity reserved for large-scale, randomised
phase III trials, we will never see meaningful changes in patient survival. 1:Personalised medicine is the mantra.
The irony is that the practices up to now are directly opposed to doing it. You can
not – for most of the randomised trials that are done, even though you get a significant
result – tell an individual patient what the chances of that treatment working for them
will be. Right, I mean, so, if you can’t do that, what you started out I mean the purpose
of what you started out to do – you’ve failed. You need more homogeneous patients so that
you can actually say for this group of fairly similar patients this particular treatment
will work. Well, you’re never going to do randomised trials once you start thinking
in that framework of needing homogeneous patients. 1:AE: Well if we don’t change the regulatory
process, what we’re already seeing is the biomedical research enterprises collapsing.
We’re seeing investments beginning to dwindle because quite frankly if you’re a venture
capitalist or an equity investor, you have far safer, quicker opportunities for a return
on investment than to engage in hoping that a molecule – that you’re going to be willing
to fund very early in it’s development – some how or other is going to make its way through
a 10-15 year process at the cost of over a billion dollars to ultimately be able to give
you a return on that investment. So we’re seeing negative consequences of not doing
something, and at the same time we also have the realisation of the incredible opportunities
if we would do something and therefore, change has to occur. 1:16:18Acceleration 1:At the current rate of development
of combination therapy, testing combinations one by one, it will take decades, and possibly
centuries to deliver more expansive cocktails to the clinic. In the face of a clinical trial
system that is clearly failing, a new line of thought is gaining traction in some oncology
circles. One man who is not hiding behind protocol, is Marc Halatsch. He founded the
International Initiative for the Acceleration of Glioblastoma Care as a framework to combine
expertise and engineer a treatment he feels will have a better chance of combating cancer’s
genetic instability. This radical work involving untested drug cocktails does not sit comfortably
within his scientific community, nor the pharmaceutical companies Marc would normally enjoy sponsorship
from. 1:We have devised a protocol
that initially involved 17 drugs. All of these drugs were chosen to act in concert against
glioblastoma to inhibit or suffocate signalling pathways that are important for glioblastoma.
We consciously avoided to identify new targets for the glioblastoma treatment. We were referring
to drugs that are approved are marketed for years for other non-oncological indications
and for which a reasonable safety profile is already available. So, the accelerated
improvement means that we are using drugs, that we want to use drugs that are already
available today, for which we already have experience with human use rather than identifying
a new molecular target and validating a candidate track for years and years and then possibly
finding out that it doesn’t work. We have a rational basis that these compounds are
effective, that they can be effective, and that they have reasonable and justifiable
risks even though we do not know how these risks adapt when these substances are combined. 1:During filming we were contacted
by a senior drug researcher for Glaxo-Smith-Klein in Cambridge England, who had been diagnosed
himself with a high grade, inoperable brain tumour. He refused to come on camera, even
with his identity hidden, but he was interested in Marc’s paper, referring to the science
behind it as ‘beautiful’. But when he travelled to a major centre for brain cancer in London,
in the hope of finding a forward thinking clinician who might prescribe him the experimental
protocol, he was told the study was ‘unscientific’. He died in 2014 leaving three young children. Well if people say the paper
is unscientific I think that it’s a judgement that cannot be accepted because the paper
is certainly not unscientific. It is making a proposal based on a set of hypothesis, and
all of these hypothesis are based on preclinical data, on what we think is robust preclinical
data. What we can say for sure is that the recent architecture of medical research for
glioblastoma patients has failed to bring out substantial improvements for these patients
and we don’t know if you can do it better, but we want to try. 1:19:54 It is no coincidence that cancer
cocktails are first coming to light in the arena of brain cancer. The limitations of
surgical intervention in the brain provide the impetus. JB: There’s a shift going on right
now in a lot of oncology where you may want to biopsy a cancer, treat for four weeks with
a mono therapy (one drug), re-biopsy that cancer, see if the genetics have changed,
treat again with a different drug for some period of time and so as the cancer shifts
and mutates, you’re changing your therapy accordingly. If you don’t do that you may
be treating according to a profile that is simple outdated because a tumour is a dynamic.
The biological situation may already have changed. JB: Now we can’t biopsy like that
in the brain. You can do that in the lung, the breast and other answers bone marrow.
So we have to figure out how’ll overcome those genetic changes that will occur with treatment. Well I believe, in the absence
of bio-marker profiles, it is very important to have a pragmatic approach and to hit multiple
targets at once so that even if there is a change in the profile and some pathways may
compensate for other inhibited pathways, you have a high chance of maintaining a higher
therapeutic pressure against the tumour. In general, multi agent protocol can be defended
by pointing out the heterogeneity of the tumour, and if you have a set of drugs that act in
concert then you have a simple rule, and the rule is, the more drugs you have the better
you probably will be able to address heterogeneity of the tumour. This is an example of the new rational
science of treating cancer, based on the lessons that cancer itself is teaching us. Yet what
Marc and his peers are pioneering, is in reality revolutionary. The pharmaceutical companies
that own the drugs he is using have refused financial support for his research, and he
is risking his professional reputation in medical circles by even publishing this paper.
Cocktails are considered radical because if such an ‘unscientific’ approach were to work
for patients, it would equate to opening Pandora’s box, with the associated danger of patients
no longer being willing to accept current medical practices. Few oncologists would be
willing to support such an investigation, John Boockvar in New York, was an exception. JB: The idea of carpet bombing a cancer
is an appropriate idea where you just bombard the tumour with multiple agents that will
come at it from different signalling pathways, much like they do with HIV medicines, and
it will take that kind of approach to see – I think – good outcomes. Of course our delivery
mechanisms, our ability to get these drugs into tumours has to be better, our immune
systems in these patients has to be augmented, improvement in immunotherapy will be an important
adjunct to any treatment, because if we cant identify mutating cells or cells that are
distinct you have no chance because chemotherapy is only going to do so much without destroying
the natural body. 1:23:19Never say die Of all the patients we met during
filming, one man’s story stood out for his exceptional courage and determination in the
face of imminent death. Anders Ferry is still fighting his disease today, 15 years after
being diagnosed with terminal cancer at the age of 32. His remarkable struggle for survival
has encompassed 6 recurrences and 5 neurosurgeries including some ground-breaking therapies and
interventions. Unable to travel alone, Anders and his father Arne travelled to London at
their own cost from the far north of Sweden, to share his story in this film. Well I have been experimenting
with my own body and taking various odd combinations of medications and non-mediations as well,
under very uncontrolled circumstances. So this has been a marathon for me and for my
wife in particular. She has seen me through extremely low points. The low points have
been really low, close to death. Ander’s original course of chemotherapy
was stopped due to the development of a severe rash, a result of sitting in a sauna trying
to raise his body temperature in order to increase the efficacy of the chemotherapy,
Anders claims this rash released him from a chemo educed mental-fog and afforded him
the clarity to do some preliminary research online. He immediately enrolled on an innovative
American trial for an early immunological compound. However, the compound was unapproved
in Europe at the time, so he had to smuggle the drugs through customs as battery electrolytes. So I was doing very well on that
treatment, but then after a couple of years they said ‘now we’re dropping the trial. Unfortunately
you won’t get anymore drug.’ And I panicked of course. I thought, well this is what has
been keeping me alive for so long so I immediately went into action to try to manufacture it
myself. As a physicist and physical chemist, it wouldn’t be difficult for me to actually
create that molecule in the lab. So I pulled all the patents and bought the chemicals,
borrowed lab resources, and my mother volunteered to be my guinea pig to try it first before
I injected it myself. At the eleventh hour, the founder
of the drug company, who had got wind of Anders’ desperate attempt to stay on the medication,
called and insisted he did not use his own acetate, instead sending him a life-time supply
of the drug the next day. By this time, it was becoming clear to Anders that this was
just the beginning of his struggle, and that the next challenge lay in combining different
treatments. Well I got the idea to do several
things simultaneously when I read Ben Williams’ thoughts on it. So I started adding little
drugs that I could access, gradually building up to a protocol that involved many drugs
in a big drug cocktail. At its peak I was taking at least 8 prescription drugs – off
label of course, they were not chemotherapies, but assigned for entirely different diagnosis
– and lots of neutraceuticals. The biggest obstacle to implement this protocol has always
been to actually find the prescription drugs. They are available but you need somebody to
write the prescription, and I have been lucky to have relatives and close friends that could
manage that for me. Sticking their necks out. And occasionally my treating oncologist has
written out a few, but very reluctantly, and has always been questioning ‘but why? Is there
any evidence for this?’ And I said ‘no, but there’s a potential in it. Evidence is weak
but there is some kind of hope. Let’s try it, I’m willing.’ As the alternative of doing
nothing, you just look at the statistics everybody dies within two years they said. Well that’s
not acceptable. By doing something proactively, possibly ruining your health, getting terrible
side effects, but also possibly getting real benefits, extending life. Like I’m here now,
a decade and a half later, I’ve got two little kids, a happy wife, a beautiful wife. My little
Lynae and Tim they are just my pride and joy of my life. So, it has worked out well for
me. Sure I have deficits, but I can live with that. Life with deficits is still life. On three separate occasions, Anders
has fought back his cancer by combining conventional surgery with innovative clinical trials, and
extensive, specifically tailored cocktails of off-label drugs and neutraceuticals. Arne F: Well concerning the oncologists,
I said ‘I’m not really satisfied’ because when Anders has his medication and it didn’t
work and the protocol didn’t work, they said ‘sorry we can’t do anymore. You go home and
play with your girl’. I put the question, who is responsible for their lives? Is it
my son who is supposed to take the care in his hand, or is it so that the oncologist
must have some responsibility? He just can’t hide behind the protocols. Ander’s fight is one that is far
from over, and yet he too spends a great deal of his time advising other patients, sharing
whatever knowledge or contacts he may have. So ever since I created my
internet persona – Andrew Yassin – and hit the internet, I’ve seen so many people come
and go on the lists. It’s terrible. Many people of whom I’ve connected so strongly to, just
pass away. It’s dreadful. Narrator asks: Do you think that those
patients were denied something? Absolutely, they were absolutely
denied the best care that could have been provided. I’m sure many more would have been
alive – or at least had a much better chance to be alive – if they had access to what I
have been doing for instance. I am also sure that this approach could apply to other cancers,
not only brain tumours. I’ve seen effect in advanced prostate cancers and breast cancers.
If I create a prescription of various off-label drugs there is a viable option of prolonging
life for a long time, and that is also including a creative and active life. I play my trumpet
at international jazz festivals. Perhaps not at the same level as I could before having
all the surgeries, but still it is a life I enjoy and the kind I’m of proud of so I’ve
done well. 1:31:49Reflections Already facing a terminal diagnosis,
should cancer patients have to shoulder the additional terror of unsupervised self-medication
in search of a meaningful attempt at survival? None of the patients we spoke to wanted to
go it alone, they desperately wanted the reassurance of professional medical supervision. Their
courage has showed us that the impossible is sometimes possible, that there could be
a solution to problems we perceive as beyond our reach. I believe the medical community
has an obligation to do research into the cause – the clinical cause of patients who
have undertaken self-medications, and who have reported extended life-span with glioblastoma.
I think it is an ethical obligation of the medical community to try to understand what
happened with these patients, how they did it, what their quality of life was and how
long they survived – these patients cannot be ignored. As survivors today, patients like
Ben, Rich and Anders stand as proof of principal. We have the unprecedented opportunity to follow
this lead, employing the gifts that science and technology are affording us to actively
embrace change. In the era of big data, Google, and Apple, society can rationally ask the
medical establishment to reconsider its confidence in a regulatory structure that served us well
in the past, but that appears slow, inefficient and even inhumane in the context of terminal
disease today. The quid pro quo, that can secure the continuation of a scientific methodology
and rational development of therapies, can be the clinical data from EVERY patient. Retrospective
analysis of this data in the era of genomics, can deliver the precious information we are
searching for in clinical trials, faster, cheaper and more accurately. Every professional I have ever
talked to, every oncologist, every neuro-oncologist, every radio oncologist I’ve talked to, believes
that I am a freak chance, that my tumour would have been put under control anyway, and that
my cocktail therapy didn’t contribute one iyota to it. They also think that Ben Williams
is a freak chance and that his 18 years would have been given to him even without his experimentation,
and anybody that lives a long time – longer than average – and uses a cocktail approach
is similarly dismissed as a freak chance. But at a certain point, people are going to
have to start looking at the evidence. Some will dismiss this evidence
as merely exceptions that prove the rule. But it is hard to dismiss as coincidence Ben,
Rich and Anders’ shared academic background and scientific training, unusual or illegal
access to prescription drugs, and the determination to overcome all obstacles in the pursuit of
their unorthodox cancer therapies. I’m quite sure that if I hadn’t
done what I did I wouldn’t be alive today. If I had simply followed the prescription
of my neuro-oncologist I would have been just another statistic, namely I would have lived
another 12-18 months and that would have been it. Because to my knowledge he never had another
long term survivor… ‘Insanity is doing the same
thing over and over again, and expecting a different result’ – Albert Einstein

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