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‘It is not necessary, in order to make great
progress in the cure of cancer, for us to

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have the full solution of all the problems
of basic research... the history of medicine

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is replete with examples of cures obtained
years, decades, and even centuries before

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the mechanism of action was understood for
these cures’ - Sidney Farber, United States

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Congress, 1971

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In 1971, when President Nixon declared war
on cancer, 1 in 30 of us would develop cancer

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in our lifetime. Today that figure is 1 in
3.

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Longer lifetimes account for a large part
of this change, but dramatic changes in our

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food chain and lifestyles contribute to this
epidemic, with the world health organisation

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forecasting a 75% increase in cancer cases
by 2030. Conversely, the cold fact is that

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despite trillions being spent on research,
we have not cured a single cancer since the

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1970s. If this is a war on cancer, then we
are staring defeat in the face. We are little

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closer to overcoming metastasis or malignancy,
the holy grails of oncology, than we were

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50 years ago. Is it possible that a tiny colony
of malignant brain cancer survivors, the most

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deadly of all cancers, hold the key to a dramatic
improvement in all cancer therapies tomorrow?

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Could the next great stride forward in the
field of oncology be simply a change in strategy

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as opposed to a new drug or technology? And
what happens if that change in approach directly

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contravenes established medical practice,
and the entire clinical trial structure we

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have built for testing cancer treatments?

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I think that many of these brain tumours and
other kinds of cancers are treatable. I just

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think that a mountain of evidence is being
over looked.

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If you face this disease and say from the
get go that it is incurable, you will always

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be right, all your patients will die, and
you have no business treating those patients

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in the first place.

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They’re trying to protect people. They inadvertently
get into a situation where they kill people.

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I would not be alive today if I had listened
to the only to the advice of my oncologist.

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Because as one point he told me that, ‘Well,
you should try to consider just staying home

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now and playing with your little daughter
while you can and not pursue any aggressive

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treatments’ … but I decided otherwise.

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Surviving Terminal Cancer

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The Everest of oncology

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The 
brain poses unique challenges for clinicians:
due to its control of every single process

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in our bodies, it is very difficult to remove
meaningful parts of tissue without removing

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meaningful functionality from the human being.
This limits the reach of surgery, radiotherapy

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and multiple biopsies, some of the most efficacious
tools at the oncologists’ disposal today.

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Furthermore, the brain sits flush within a
fixed volume cavity - the skull - and so the

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swelling that is the by-product of carcinogenosis
is frequently the primary cause of death in

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brain tumour patients as inter-cranial pressure
builds relentlessly. Finally, clinicians treating

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the brain face a unique impediment in something
called the blood brain barrier: a natural

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and virtually impenetrable biological coat
of armour which protects brain cells from

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infections circulating in the body. If we
didn’t have such protection then a simple

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cold could easily end our life. However, when
placed in the context of cancer, this protective

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coat of armour makes it difficult to get chemotherapy
into the brain. These three aspects of neurology

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make clinical practice in the field of neuro-oncology
the most severely challenging of any in oncology

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today. Compared to other cancers, brain cancer
has a very low profile, and yet it claims

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more young lives than any other cancer. Nobody
survives it’s most aggressive and lethal

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form, glioblastoma multiforme, referred to
in medical circles as ‘the terminator’.

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Part of this is because of the difficulty
we just described in treating the brain. But

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brain cancer itself is differentiated from
more common cancers by it’s cellular heterogeneity:

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this means it’s highly differentiated cell
populations are inherently complex and varied,

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and so simple targeted treatments affecting
only some areas can not impact it’s overall

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ability to mutate and proliferate. A complex
problem calls for a complex solution, and

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biological heterogeneity demands therapeutic
heterogeneity: or more simply brain cancer

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is telling us that each patient is has a different
disease, and that they need a different cure.

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This genetic instability is the hallmark of
all cancers. In this sense, cancer is the

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most terrestrial of diseases, starting as
a simple malfunction of a living organism,

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it demonstrates the same remarkable capacity
for adaptation and change, that has defined

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of all the great survivors of evolution. It
is this ability to modify it’s DNA structure

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from generation to generation that results
in the phenomenon referred to as drug resistance

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- the principal barrier to treating cancer.
All of these facts, the limitations of traditional

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intervention methods when dealing with the
brain, cancer’s most sinister characteristics,

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and then additional problems specific to brain
cancer, are acknowledged and agreed upon by

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every hospital and every expert in the world.
The tragedy for brain cancer patients today

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is that the care they will receive does not
come close to reflecting the scientific knowledge

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now at our disposal. This is where the problems
facing brain cancer, if they could be solved

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today, could revolutionise the treatment of
all cancers tomorrow.

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‘A round trip to Hades’

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In southern California an academic and scientist
has dedicated his life to pursuing better

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outcomes for brain tumour patients since being
diagnosed himself in 1995 with the most aggressive

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type of brain cancer, glioblastoma multiforme.
Given only a few months life expectancy, Professor

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Emeritus Ben Williams was an extraordinary
patient, and now nearly two decades later,

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he is an extraordinary survivor for patients,
his book Surviving Terminal Cancer is a source

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of frank assessment and logical analysis of
all available treatment options, often lacking

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from their own medical team. Every year, Ben
updates this invaluable source of information

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making it freely available to any patient
surfing the internet via a national brain

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tumour charity. His remarkable journey has
taken him from moribund patient, to highly

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respected survivor and patient advocate.

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When I was diagnosed with brain cancer I knew
almost nothing about the disease other than

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that it is one of the worst medical diagnosis
you can get. My first reaction when I heard

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of that was to basically have a shiver down
my spine because I knew I probably didn’t

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have much chance of surviving. I hadn’t
even heard of a glioblastoma at that point.

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I was told that it was the worst kind of tumour
you could have and that nobody survived it.

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For the first couple of weeks after that I
was just in shock. I mean there was no other

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way to describe it.

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Ben was told he could expect to live for 12-18
months if he was lucky, and that the chemotherapy

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treatment available to him would not save
his life.

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For the first several months, most of my thinking
was, you know well, I’m going to die. How

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am I going to deal with it? And I thought
a lot about death. The treatment was just

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sort of something I was just following along
because I didn’t know any better at that

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point. There were no options that were presented
to me. What you are faced with is well, I

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don’t really have a choice. This is going
to kill me and I better try and figure out

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how to make that as easy a process as possible.

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Like all patients Ben was prescribed the standard
of care: immediate surgery, followed by intensive

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radiation and chemotherapy.

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When you receive a diagnosis that every one
tells you is terminal - that no one survives

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it - it’s impossible not to become depressed
by that information. I mean I look at pictures

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from that period of time and I mean, clearly
I was depressed and it wasn’t until I began

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doing research that said there was a possibility,
that there are things you can do that would

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be helpful and I began to think - well this
is worth at least making the fight. And the

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more information I began to find, the less
depressed I became, and the more optimistic

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that things were not nearly as terrible as
everyone was telling me.

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However, before the era of the internet, Ben’s
task of educating himself quickly was considerable.

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The first couple of months I basically did
nothing else but reading. It was a crash course.

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I knew I didn’t really have much time to
do a comprehensive education so I was really

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trying to find a shorthand account of what
I was dealing with. Unfortunately most of

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the articles were every bit as discouraging
as what I had been told initially as they

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almost all began with an introduction that
said glioblastoma is universally fatal. But,

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the more research I did, the more leads that
I came across about things that had been ignored

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and things that - at some early stage data
from clinical trials that really hadn’t

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gotten much attention but still looked quite
promising and - it seemed like it was totally

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sensible to try and add those things into
whatever else I was being prescribed to do.

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So I found, you know, several different drugs
that had good evidence from medical literature

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of benefitting people with cancer - some of
them specifically with brain cancer but others

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with cancer in general. I mean things like
(<i>immune stimulants</i>) and things that were

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used widely else where so that I found one
mushroom extract that was used in Japan routinely

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in almost all cancer treatment protocols and
yet it is never mentioned in the United States.

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It has zero toxicity. Why would you not use
it? I mean millions of people in Japan use

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it. That’s a big mystery to me. How you
can just disregard something that has credible

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evidence.

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But Ben's line of thinking was met with surprising
opposition.

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My neuro-oncologist raised the question - well
you don’t want to add these things because,

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you know, they have a lot of toxicity and
I thought, well not from what I know about

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them compared to what you’re about to give
me. And it turned out that while I had some

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side effects of some of the things they were
really nothing of major consequence so I was

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right about the idea that they were worth
trying.

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With a PHD from Harvard and a chair as Professor
of experimental psychology at the University

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of California, Ben had the courage of his
convictions, a critical tool the vast majority

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of patients lack.

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I realised fairly early that medical practice
is standardised for everyone and pays almost

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no regard for the individual variability of
patients. When I first asked my oncologist

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- my neuro-oncologist - if I could add the
first agent that I used - it was high dosage

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Tamoxifen - to what he was offering in terms
of a chemotherapy program. He just out right

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refused. He was unwilling to bend and we had
a major altercation over the phone and it

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ended up with him basically saying that we
couldn’t work together and so whether he

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fired me or I fired him, I was without a neuro-oncologist
at that time. But fortunately my neurosurgeon

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intervened and convinced my neuro-oncologist
that maybe they should let me do a little

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bit more in terms of participating in my own
treatment program than they would ordinarily

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do. Eventually we got along quite well but
I never did really tell him everything I was

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doing after that. Going against the advice
of my doctors was really initially an act

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of desperation. I mean, I wasn’t concerned
about offending them, I was concerned about

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staying alive and so I was going to use anything
I could get my hands on, and if that made

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them angry, well that was too bad. At one
point I was going down to Mexico, to Tijuana,

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to obtain a drug normally used for acne which
also had been shown to have some treatment

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benefits for glioblastomas. I had to go to
Mexico because the drug required a prescription

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and I knew it was going to be a great difficulty
obtaining it here so I was taking that all

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along without the knowledge of my neuro-oncologist.
The irony was that when I eventually told

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my neuro-oncologist what I had done, he said
to me ‘that was a very nice study that MD

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Anderson did’ – he knew about it all along,
but it was not a part of the standard treatment

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and so he’d never even mentioned the possibility.
In most cancer treatment protocols there is

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a standard treatment that the oncology community
has agreed upon and they don’t deviate from

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it except in the context of clinical trials.
That realisation, the beginning of my deep

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anger about how the medical system was working
- It made absolutely no sense to me not to

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use everything that might have a benefit as
long as the toxicities were acceptable. Why

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wouldn’t anyone want to add them? It seemed
to me totally irrational that people didn’t

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use everything that was available.

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With this strategy Ben constructed a cocktail
of drugs around his chemotherapy. When his

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MRI scans began to show his tumour gradually
reducing in size, and eventually disappearing

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altogether 6 months later, it was clear that
something very unusual was taking place.

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After my first round of chemotherapy I did
get a small amount of shrinkage in my tumour.

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That was a tremendous weight that was lifted
off of me. I mean I didn’t feel of the kind

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of depression that I had felt up until that
time. I mean, I was ready for the battle at

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that point because it didn’t seem hopeless.
So I started adding even more things at that

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point. And then after the second round of
chemotherapy I had a lot of progression in

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the tumour, and then after the third round
of chemotherapy, a lot more. Then I had a

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clean MRI after the fourth round. And I’ve
got clean MRIs ever since. People are always

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raising the question - so this might have
worked for you, but maybe you were just a

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rare case that responded to chemotherapy’?
Did any of these other things that you added

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make a critical difference? The hallmark of
my case was that the chemotherapy did work

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for me. I mean, I had something was different
about how I was getting the chemotherapy and

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the things that went with it, and I had deliberately
focused on that. I mean, I though seriously

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about where the resistance to chemotherapy
came from and how one might overcome it.

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Now retired, Ben spends a great deal of his
time responding to the desperate enquiries

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of patients who have read his book, offering
impartial advice whilst never advocating specific

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treatments.

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We’ll never know for sure why I’m still
alive. Certainly I did things that were unusual,

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but, you know, I might have done things that
were unusual in terms of the characteristics

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of my tumour. I don’t think that’s an
argument I take seriously now because I have

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advised a lot of people over the years to
adopt a similar approach. They didn’t do

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exactly what I did, but they added as many
things as they could to the standard treatment

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- and many of them have had very good success.
The irony is that almost all oncologists agree

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that multiple agent approaches are going to
be necessary to actually cure anything. And

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so, no one really is disputing that. The question
is what goes into those cocktails and what

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kind of criterion of evidence that you have
to have for putting those cocktails together.

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To this day Ben still self-administers a maintenance
therapy: a daily cocktail of vitamins and

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supplements designed to try and create as
hostile an environment as possible for cancer

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to face in his body.

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Logic Dictates

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On the east coast of America, an advocate
of combination therapies is Dr Raymond Chang.

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Pioneering the integration of oriental and
western medicine, his book Beyond the Magic

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Bullet poses an uncomfortable question for
the oncology community.

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Oncology thinking somewhat followed infectious
disease treatment thinking because the first

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original breakthrough in achieving a cure
for any disease came in the infectious disease

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field whereas possible with the discovery
of penicillin and so fourth. Single antibiotics,

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single chemical (*) were able to eradicate
– cure, literally - serious medical conditions

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like tuberculosis, like syphilis. That was
then applied to cancer with the same logic

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behind it… well if we find the right chemical,
maybe we can eradicate cancer just like we

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can eradicate tuberculosis… and then that
mode of thinking dominated (*) therapy for

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over a century at least. We think that most
diseases, if you simply find the right key,

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you should be opening the door, and the reason
why the door remains locked - the cure remains

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locked - is because we don’t have the right
key. So we should keep looking for new keys

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or try to improve the key that we have and
we will eventually open the door. What if

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this door has multiple locks? When you keep
looking for one key, it’s not going to open

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the door no matter how hard you look. It will
never, it will fail, the whole strategy of

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research will fail! Then maybe the way of
thinking is wrong. It’s not that we need

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better drugs, but we need to know better how
to deploy what we have already. If we have

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‘cure’ or ‘control’ already in our
hands except that we’re not using things

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properly.

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As proved to be the case with childhood Leukaemia
and aids, it was the combination of existing

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treatments that delivered the breakthrough.
Today infectious disease treatments follow

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this logic.

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Hepatitis C, hepatitis B - chronic viral infection
- HIV obviously. They are all attacked with

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multi(*), multi agent, multi target approaches
– and with success. Cancer treatments are

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kind of behind… again. So hopefully it will
follow the lead of the infectious disease

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practitioners.

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The idea of a cocktail approach to cancer
treatment has gained adherence amongst the

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oncology community.

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I think that if we are going to try to treat
this disease we need to be using combination

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therapy from the get go. Single agent therapy
is not likely to be very effective with a

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disease with so many molecular (*) underlying
its ability to be invasive and resistant to

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therapy.

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What you want to design for a problem like
cancer is not a drug or an intervention. You

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want to design a solution - because that’s
what patients want. So it’s a lot like your

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computer: there’s amazing components in
there like your microprocessor or your hard

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drive, but individually they aren’t worth
anything to you until they are put together

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into an interoperable system that becomes
your laptop that’ll do word processing or

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send emails… Now that’s of value to you.
Today in drug development and in clinical

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research we need to be thinking of those kinds
of integrated, interoperable solutions.

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With glioblastoma we’re really climbing
a mountain. Every therapy that we see a modest

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success for gets us a little bit further up
the mountain then we set up a new base camp,

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and then we come up with a another therapy
that gets us further up the mountain, set

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up a new base camp. The concept of synergy
is really important here because what if we

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could just get further, faster?

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An example of why it is that combining different
treatments together is in fact the development

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of what is now the standard of care: It used
to be that you used to receive radiation first

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and then wait a month or so, and then start
on your chemotherapy. The new protocol is

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that you have the radiation and the chemotherapy
together. It has produced a better outcome.

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Clearly the change of putting them together
simultaneously as opposed to sequentially

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was a step in the right direction.

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Current management of brain cancer as well
as many other cancer conditions involves a

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multi disciplinary approach where surgery
is deployed, radiation is deployed, chemotherapy

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is deployed, and targeted therapies are deployed.
So one can argue that it is already, in a

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way, it’s already mixed or cocktails and
not just one single therapy… But, much more

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can be done. Many other drugs can be used
without much toxicity without much even cost.

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Simple, simple drugs.

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Although there is general consensus of the
advantages of the cocktail approach, there

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is disagreement about how much information
is needed to start combining untested treatments

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together. How far and how fast this can be
taken for individual patients is the fundamental

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issue.

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The big problem with cancer treatment is that
the tumour develops resistance. I mean, you

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know, so it’s usually that the treatment
is only partially effective in the beginning

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- at best - and what you then get in an evolution
of resistant strains of the tumour, and so

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the more you treat it, the more resistant
it gets just through the process of evolution.

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The biggest risk in all of this is you’re
going to be dead very quickly from your tumour

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unless you do something other than what is
being offered from the conventional medical

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treatment.

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We always balance the potential gain with
the potential toxicity of an agent and making

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a decision whether to include it and if so,
how to include it and when to include it…

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but we’re not treat colds, we’re treating
glioblastoma… and what risks you might take

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with a cold are going to be far less than
the risks you are willing to take with someone

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with a glioblastoma when you know the natural
outcome is so dire.

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It is clear that cocktail therapy represents
an excursion into the unknown, with corresponding

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uncertainties about the risks involved.

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Some of these cocktails involving 10 or more
substances can have life threatening complications

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and for the safety of the patient it would
be much better if the physician knew about

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it and could appropriately follow. There can
be some aggressive attitude of some physician

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starts experimental treatments especially
with free purpose, non approved drug cocktails.

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And I can very well understand that patients
may try to avoid this conflict with a treating

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physician and I think that the solution is
on the side… lies on the side of the physician.

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Resistance

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Treating malignant brain tumour patients is
not easy for physicians. Most do not become

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doctors to watch all their patients die. At
the sharp end of this scale lies paediatric

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neuro-oncology. In Belgium, one man’s professional
crusade against brain cancer has led to his

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university hospital becoming the most advanced
centre in Europe for immunotherapy in brain

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cancer. When not fund-raising out of hours
to support his research programmes, Professor

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Stefaan Van Gool is on the very front lines
of neuro-oncology, taking the fight patient

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by patient.

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Personally I think the prognosis of the patient
is the worst when the doctor does not treat.

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There is nothing. If there is one thing frustrating
that is that you want to fight for your patient

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but that you face borders that are aimed to
be protecting patients, but are sometimes

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also not protecting patients because they
block progression. Evidence based medicine:

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you do an intervention, compare to control
- but if this intervention consists of five

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new factors… that will be a hard one to
do, but maybe these 5 (*) factors are needed

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to make the progression. That’s the difficulty
more and more. You have to fight against all

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the barriers with (*) committees, with regulatory
authorities, which makes thinking out of the

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box more and more difficult. If we come too
much into fixed system: phase one, phase two,

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phase three, phase four, and that’s it.
That will reduce progression - certainly if

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you want to elaborate multi model, more holistic
approaches. That’s very difficult and unfortunately,

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at the moment, it becomes more and more difficult.

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The reality facing the vast majority of patients,
is that their doctor will not engage with

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any experimental therapy outside of a clinical
trial, even in the context of a terminal diagnosis.

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We wanted to try and understand the reasons
behind this seemingly unnecessary resistance.

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Realistically there are other practices beyond
medicine. It has to do with capitalism, it

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has to do with health care structures, systems
and so fourth. Mono therapy is easier to carry

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out. If something goes wrong, it is clear
what’s wrong because you’re giving one

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treatment at a time so if the patient has
a server side effect it’s that treatment

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- it’s that drug. Regulatory wise, it’s
very difficult to get studies going involving

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multiple agents, because let’s say if you’ve
got five agents - instead of testing one thing

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at a time then you have to test A against
B plus C plus D plus E or, A plus B against

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C plus D plus E. There are then, to the power
of five, so many different variations possible.

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That means you have to do so many studies.
Practically it’s almost impossible to study

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these things if it becomes complex. So a simple
monotherapy approach is easier, cleaner for

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management purposes - but it may not be as
effective. It is unconscious because doctors

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don’t necessarily think about it, but they
implement it in this fashion. This is the

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way how studies are done. You don’t put
patients on three new X, Y, Z unknown new

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treatments at the same time because the issue
always comes up that well, if it works, what

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did it? Then we don’t know. That is not
acceptable to science. You have to be careful

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that the doctors need to be scientific…
but when you’re treating the patient, is

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it for science or is it for the patient? Sometimes
we forget.

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Other obvious candidates for cocktails are
natural compounds. These naturally occurring

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substances cannot be protected by patent and
so no one company can gain a monopoly over

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their supply. Totally non-toxic, and with
years of data to prove its efficacy in cancer

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care, curcumin should be an obvious adjuvant
for any cancer protocol, and yet it is rarely

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used in western medicine. We travelled to
the world’s largest specialist cancer hospital,

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MD Anderson in Houston, where the series of
laboratories dedicated to natural compounds

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are testament to the holistic vision behind
the Texan project.

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As of today there have been over 150 clinical
trials that have been completed. And the answer

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is yes it works and it down modulates bio-markers.
You know, there are only 20-25 driver genes,

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and that I have taken all those driver genes
and asked ‘are they down modulated by curcumin?’

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Because that is what the drug industry is
targeting…and the answer is yes: curcumin

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alone, has over ninety different targets,
ninety different targets, it is not just a

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mono-targeted. So this is what the drug industry
calls a ‘dirty drug’. Any drug that hits

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more than one target is a dirty drug for them,
they don’t like it. There are only two rules

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of the game that I have learnt from my days
in Genentech (and there is no third that I

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know of) .. Safety: number one, whatever you’re
giving to the patients should be absolutely

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00:30:00,279 --> 00:30:07,279
safe, it shouldn’t hurt them in any way.
Second is the efficacy. There is no third

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rule, and curcumin meets both of them.

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But as any cancer patient will testify, there
is huge opposition from the medical establishment,

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towards adding natural compounds to traditional
cancer treatments. The reason most patients

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are given, is that it ‘may interfere with
your treatment’ although only in rare cases

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is there any evidence to support this claim.

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In medicine today, there is a buzz word and
that is called ‘targeted therapies’. Targeted

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therapy means you pick a single gene, a single
protein, and you try to find an inhibiter.

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That is what they call a ‘magic bullet’.
They have come up with a lot of magic bullets.

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Only thing is, these are not bullets and these
are not magic, so there is a lot of frustration,

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asking where did we go wrong? Where they did
go wrong was thinking that cancer is a single

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00:31:04,700 --> 00:31:11,700
gene or single protein - a single target disease.
By now, we are living in the era of ‘omics’:

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genomics, proteomics, metabolomics, and all
of that is out there to tell you that cancer

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is a multi-genic disease. No matter which
direction I look at, people’s mind is set,

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00:31:25,919 --> 00:31:30,990
and their mind is set on targeted therapies.
They want a targeted therapy, if it is not

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targeted they are not interested, period.
It doesn’t matter whether it does anything

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good for the cancer or not, they are not interested…
and that’s where I face the biggest resistance.

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I have people tell me point blank in my face,
right here in MD Anderson. They say, ‘well

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00:31:48,929 --> 00:31:52,360
Dr Aggarwal, anything you do with respect
to natural products I don’t believe even

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00:31:52,360 --> 00:31:59,360
one bit of it. They don’t even want to read…
and we publish in the same journals. We are

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00:31:59,779 --> 00:32:06,779
most highly cited. People don’t want to
read. There’s this, you know, in born bias.

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My problem with the ethics of oncologists
is that they want to pre-empt the decision

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00:32:17,039 --> 00:32:23,399
and they don’t their patients have any leeway
in making a decision that sort of kind of

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00:32:23,399 --> 00:32:27,970
moves them in the direction of alternative
medicine. It’s a real concern on their part.

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I mean, professional reputations can quickly
be ruined if you’re viewed as one of those

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00:32:36,019 --> 00:32:43,019
kooky guys who goes around trying to throw
out anything under the sun into your treatment

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00:32:44,909 --> 00:32:48,009
protocol.

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History is littered with scientific breakthroughs
that were castigated for their implications

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for the prevailing status quo. When Copernicus
introduced his heliocentric theory to the

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world, the shock to the belief system reverberated
for centuries afterwards: Gallileo Gallilei

355
00:33:03,429 --> 00:33:07,789
was persecuted for his acknowledgement of
Copernicus’ theory and his pursuit of a

356
00:33:07,789 --> 00:33:14,179
new rational science in its wake. Even Gallileo’s
presentation of his new invention, the telescope

357
00:33:14,179 --> 00:33:19,750
and it’s irrefutable new evidence, could
not dampen the fervour of his condemnation.

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In the nineteenth century, Ignaz Semmelweis,
a relatively unknown doctor, a Hungarian practising

359
00:33:25,370 --> 00:33:30,570
in the venerated hospitals of Vienna at its
empirical peek, noticed an alarming correlation

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between the new practice of pathology, and
the advent of a series of deaths of both mothers

361
00:33:35,039 --> 00:33:40,649
and babies in the maternity wards of those
same hospitals. His suggestion that perhaps

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00:33:40,649 --> 00:33:45,730
his fellow surgeons should consider using
chlorine to wash hands before operating on

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00:33:45,730 --> 00:33:52,240
patients, was met with vicious resistance.
Unable to substantiate his theory scientifically,

364
00:33:52,240 --> 00:33:56,509
Semmelweis was ostracised professionally by
his peers for daring to question the status

365
00:33:56,509 --> 00:34:03,509
quo. He died 15 years later in a mental institution,
a broken man, yet a century and a half later

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00:34:05,799 --> 00:34:11,219
he is venerated as a national hero in Hungary,
where statues and coins carry his legacy as

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00:34:11,219 --> 00:34:17,719
the father of sterile medicine. Today, the
Semmelweis reflex is a term used to describe

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an illogical and exaggerated response to a
challenge to the prevailing dogma. Unfortunately

369
00:34:23,580 --> 00:34:28,159
- the Semmelweis reflex is alive and well
in today’s medical establishment: Barry

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00:34:28,159 --> 00:34:33,599
Marshall, a little known doctor from Western
Australia, had identified a bacteria in the

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00:34:33,599 --> 00:34:39,579
early 1980s that indicated stomach ulcers
were caused by bacteria. This was heresy to

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00:34:39,579 --> 00:34:43,739
the established thinking in the field of endoscopy,
which was convinced that stomach ulcers were

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00:34:43,739 --> 00:34:50,129
caused by stress. As a result Marshall’s
thesis was not published in any medical journals

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00:34:50,129 --> 00:34:54,389
and sat on the shelves gathering dust while
hundreds of thousands of patients across the

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00:34:54,389 --> 00:35:00,660
world had their stomachs removed, unnecessarily
so according to his theory. With the bacteria

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in question only able to develop in primates,
but with testing on primates prohibited, the

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00:35:06,290 --> 00:35:10,800
successful animal experiments that the medical
establishment deemed pre-requisite for Marshall

378
00:35:10,800 --> 00:35:16,680
to progress to human trials, could thus never
be completed. So locked out of both animal

379
00:35:16,680 --> 00:35:21,990
and human experimentation, but convinced of
his theory, Marshall chose to experiment on

380
00:35:21,990 --> 00:35:28,270
the one human he did have legal access to:
himself. In front of an audience of stunned

381
00:35:28,270 --> 00:35:33,460
peers, he downed a petri dish full of bacteria
grafted from a patients’ stomach, and claimed

382
00:35:33,460 --> 00:35:39,930
to have infected himself with a stomach ulcer.
The proof duly came, as did his cure without

383
00:35:39,930 --> 00:35:44,530
the need to remove his stomach, swiftly followed
by an avalanche of awards and praise from

384
00:35:44,530 --> 00:35:51,530
the establishment, culminating with the Nobel
Prize in 2005. Beyond the more obscure issue

385
00:35:52,910 --> 00:35:58,319
of medical hegemony, lie more obvious reasons
for why combination therapies do not reach

386
00:35:58,319 --> 00:35:59,030
patients.

387
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If you have: a drug A from company A, and
a drug B from company B, and a drug C from

388
00:36:05,599 --> 00:36:11,040
company C, it is extremely difficult to get
all three of those drug companies together

389
00:36:11,040 --> 00:36:17,960
to agree to use their drugs to treat a particular
disease process. It’s much easier if the

390
00:36:17,960 --> 00:36:24,869
drugs all come from one company… and that
is a fundamental challenge that not just neurosurgical

391
00:36:24,869 --> 00:36:31,099
patients with glioblastoma face, but all cancer
patients face. And from the company stand

392
00:36:31,099 --> 00:36:36,359
point one could make a good argument that
it’s reasonable and understandable that

393
00:36:36,359 --> 00:36:40,920
this is the case because they invest hundreds
of millions, sometimes billions of dollars

394
00:36:40,920 --> 00:36:46,839
to develop that drug, and as that drug comes
to market it goes to the FDA, the application

395
00:36:46,839 --> 00:36:52,510
of that drug to other disease processes in
combination with other drugs could cause a

396
00:36:52,510 --> 00:36:56,970
lot of problems for them. So it’s a very
difficult thing to address.

397
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On top of the reluctance of western medicine
to consider natural products as they cannot

398
00:37:00,770 --> 00:37:07,500
be patented, for the very same reason, drugs
whose patent has expired are similarly discarded

399
00:37:07,500 --> 00:37:13,599
as they cannot guarantee a return on the investment
required to run a clinical trial. This results

400
00:37:13,599 --> 00:37:19,069
in a large number of drugs with strong laboratory
evidence for anticancer properties never getting

401
00:37:19,069 --> 00:37:25,480
anywhere near patients. In some cases, even
when human trials have been run it is still

402
00:37:25,480 --> 00:37:28,060
not enough to bring the drug into the mainstream
treatment.

403
00:37:28,060 --> 00:37:33,410
A very nice example is the use of the old
malaria drug which is dirt cheap, Chloroquine,

404
00:37:33,410 --> 00:37:40,410
for brain cancer where nice trials have been
carried out showing improvements up to 50%

405
00:37:42,619 --> 00:37:49,619
survival time when it’s added to standard
chemotherapy. It has almost no side effects.

406
00:37:50,369 --> 00:37:56,510
It’s one pill a day. It does not mean the
patient has to suffer going to the hospital,

407
00:37:56,510 --> 00:38:03,510
get a drip, any of this. It’s dirt cheap.
Why not? Well, FDA has not approved its use

408
00:38:05,940 --> 00:38:12,940
for this condition - for one. The information
is not widely disseminated. There’s no big

409
00:38:12,940 --> 00:38:19,940
drug company behind the manufacture of chloroquine
to market it for this use. Nobody makes much

410
00:38:20,290 --> 00:38:25,400
money if suddenly every brain cancer patient
starting taking chloroquine, it adds very

411
00:38:25,400 --> 00:38:29,880
little to the bottom line of any particular
business or company.

412
00:38:29,880 --> 00:38:35,920
So it is more and more important for us to
look at these drugs that have been left on

413
00:38:35,920 --> 00:38:40,079
the shelf, that big pharma wants nothing to
do with, but we don’t initially have the

414
00:38:40,079 --> 00:38:47,079
time or the resources to provide the data
managers, the IRB fees and start up fees that

415
00:38:48,940 --> 00:38:51,750
it takes run a good clinical trial.

416
00:38:51,750 --> 00:38:56,250
Aside from the influence of the medical world
status quo, and the economic reasons hampering

417
00:38:56,250 --> 00:39:01,589
development of combination therapies for cancer,
there is a strong feeling amongst the patients

418
00:39:01,589 --> 00:39:08,349
we interviewed as to why oncologists are unwilling
to deviate from established best practices,

419
00:39:08,349 --> 00:39:11,240
even in the context of terminal disease.

420
00:39:11,240 --> 00:39:18,240
One of the problems from a patient’s perspective
is that they want as many drugs as possible

421
00:39:19,109 --> 00:39:24,900
to facilitate long tern survival, and that’s
a very reasonable request from the stand point

422
00:39:24,900 --> 00:39:30,020
of a patient. If you have cancer, you hear
a certain drug might be effective in your

423
00:39:30,020 --> 00:39:34,390
particular type of cancer, you want to access
that drug. You hear that another type of drug

424
00:39:34,390 --> 00:39:38,339
might be effective, you want to actually just
go ahead and combine those drugs, and so fourth

425
00:39:38,339 --> 00:39:44,540
and so on. From a patient’s perspective,
you are entitled to pursue any type of therapy

426
00:39:44,540 --> 00:39:51,119
you want to. From a provider’s perspective,
from a neurosurgeon, a scientist, from a a

427
00:39:51,119 --> 00:39:56,240
neurosurgical oncologist’s perspective,
we have to be very, very careful about what

428
00:39:56,240 --> 00:40:02,069
we recommend to patients in terms of going
after therapies that are unproven.

429
00:40:02,069 --> 00:40:09,069
Doctors are judged by so-called standards
of practice in the community. So, if in California

430
00:40:09,800 --> 00:40:14,150
this is the way we do things, here, in LA,
this is the was we do things… and you do

431
00:40:14,150 --> 00:40:19,380
it differently and the patient gets hurt,
and you’re in court, they will summon your

432
00:40:19,380 --> 00:40:24,839
peers and say well, how do you do things usually?
And every body says ‘I don’t use Temodar,

433
00:40:24,839 --> 00:40:26,660
I don’t do Temodar + chloroquine

434
00:40:26,660 --> 00:40:33,440
This issue of liability is one of the silent
enemies in the war on cancer. Drs and hospitals

435
00:40:33,440 --> 00:40:37,710
who would willingly take more risks for their
patients who have run out of options, are

436
00:40:37,710 --> 00:40:44,300
discouraged from doing so by fear of malpractices
suits. This fear of prosecution is not limited

437
00:40:44,300 --> 00:40:49,559
to doctors, but runs deep through the entire
system, dissuading individuals and teams from

438
00:40:49,559 --> 00:40:51,160
doing anything outside of the box for their
patients.

439
00:40:51,160 --> 00:40:58,160
The specialists are at major cancer institutions
that does not treat patients as individual

440
00:40:59,270 --> 00:41:06,270
unlike what patients may think. They treat
as a group. They can call it a team approach,

441
00:41:08,650 --> 00:41:15,650
but they treat by committee, literally there
is a committee of doctors who review cases

442
00:41:15,799 --> 00:41:22,799
– it’s called a tumour board – and almost,
you can imagine, 6,7 specialists at the centre

443
00:41:23,650 --> 00:41:30,569
every week, sit down and go over new cases
and decide ‘this is what we’re going to

444
00:41:30,569 --> 00:41:36,530
do.’ Now, that also creates an issue because
then everybody has to agree for one, then

445
00:41:36,530 --> 00:41:43,530
of course what everybody agrees on in any
bureaucratic structure has to be the lowest

446
00:41:44,900 --> 00:41:50,589
common denominator. Okay? But that’s the
safest way for the doctors and the hospital

447
00:41:50,589 --> 00:41:56,730
because if there was a problem, and if the
was a charge, they say well, ‘six specialists

448
00:41:56,730 --> 00:42:03,000
had a committee meeting on the same week – and
we all agreed… you want to sue six of us?

449
00:42:03,000 --> 00:42:07,339
And we represent the hospital are you going
to sue the whole hospital for this decision?

450
00:42:07,339 --> 00:42:12,369
every one of our patients get exactly the
same thing. What’s wrong with this? We are

451
00:42:12,369 --> 00:42:18,609
following the guide lines from the American
cancer society’. So, everything is therefore

452
00:42:18,609 --> 00:42:25,609
protected, protected, protected… for liability
reasons. So it’s fool proof. If you try

453
00:42:25,619 --> 00:42:30,890
to be individualistic, stick your neck out,
give chloroquine because there’s a paper

454
00:42:30,890 --> 00:42:36,369
that says give chloroquine, and something
goes wrong, you don’t have anything backing

455
00:42:36,369 --> 00:42:43,369
you up in the court of law. It’s much safer
to follow a protocol. A protocol is one thing

456
00:42:43,890 --> 00:42:50,440
at a time until it’s proven otherwise. The
proof may never come because there is no funding

457
00:42:50,440 --> 00:42:57,440
to try to prove these things. Who gains from
proving them? Who is going to fund the proving

458
00:43:00,000 --> 00:43:07,000
of this? These are much larger issues that
I think will hamper developments of true cocktails

459
00:43:12,530 --> 00:43:19,530
unless there is radical changes in health
care systems and social systems. It may not

460
00:43:21,349 --> 00:43:22,670
come.…

461
00:43:22,670 --> 00:43:27,940
Lightening doesn’t strike twice

462
00:43:27,940 --> 00:43:32,700
Ben's Williams book is nothing more than a
blueprint for anyone who wants to follow a

463
00:43:32,700 --> 00:43:39,520
more pro-active approach to their own treatment.
One such patient was Richard Gerber, a fellow

464
00:43:39,520 --> 00:43:44,650
American academic living in Italy, who was
diagnosed with the same lethal brain tumour

465
00:43:44,650 --> 00:43:51,069
a decade after Ben. Given just months to live,
Rich had nothing to lose.

466
00:43:51,069 --> 00:43:58,069
During the chemotherapy and radiotherapy that
I had – although it was very exhausting

467
00:43:58,400 --> 00:44:05,400
– I started reading at night, articles and
journals, and I realised that therapy was

468
00:44:06,750 --> 00:44:13,750
not going to really make my life any longer
so I started doing research into alternatives,

469
00:44:18,200 --> 00:44:23,780
and little by little, on the internet, I came
across this name ‘Ben Williams’ who had

470
00:44:23,780 --> 00:44:30,520
written a book. I ordered the book. And it
basically is teaching people to take their

471
00:44:30,520 --> 00:44:37,520
matters into their own hands and to be their
own doctors in part. So far, this cocktail

472
00:44:38,550 --> 00:44:45,550
approach that he writes about in his book
has proved efficacious for me. I wasn’t

473
00:44:45,859 --> 00:44:52,859
just blindly following Ben. In fact, I wouldn’t
have followed Ben at all if his arguments

474
00:44:53,069 --> 00:44:55,300
weren’t logically convincing.

475
00:44:55,300 --> 00:44:59,910
In common with Ben, Rich shared a scientific
background, he is an expert at developing

476
00:44:59,910 --> 00:45:01,690
solutions for complex problems.

477
00:45:01,690 --> 00:45:08,690
I took what we call a ‘black box’ concept
that is glioblastoma is a very, very complicated

478
00:45:11,130 --> 00:45:17,569
phenomenon. Nobody knows: how it works, how
it grows, how it gets started, how the therapy

479
00:45:17,569 --> 00:45:24,569
works, and papers are published on very specific
subjects and very specific genetic pathways,

480
00:45:25,710 --> 00:45:32,710
but there is no integration of this information.
So, my approach was based on finding as many

481
00:45:34,220 --> 00:45:40,059
agents which could block assorted pathways
which activate glioblastoma, and doing it

482
00:45:40,059 --> 00:45:47,059
all at once so that the glioblastoma would
have less of a chance to mutate and escape

483
00:45:47,230 --> 00:45:51,579
via a path way because I would already be
blocking that pathway.

484
00:45:51,579 --> 00:45:57,440
Of course, assembling and consuming an unsupervised
and untested cocktail of drugs and neutraceuticals

485
00:45:57,440 --> 00:46:02,930
is daunting even for someone with an in depth
appreciation of their disease. One of the

486
00:46:02,930 --> 00:46:09,380
patients we interviewed equated it to playing
Russian roulette whilst on death row.

487
00:46:09,380 --> 00:46:16,380
My doctor was a very sympathetic oncologist,
but she was very ‘by the book’. She didn’t

488
00:46:17,960 --> 00:46:24,960
want me to do anything else. Coming up with
my own notions I suggested to this doctor

489
00:46:25,500 --> 00:46:31,530
that I would like to take melatonin. I tossed
this out as sort of a test because at the

490
00:46:31,530 --> 00:46:36,500
time I was actually taking 10 or 15 other
pharmaceuticals but I thought I would start

491
00:46:36,500 --> 00:46:41,410
small and she didn’t want to hear about
it. She told me not to take melatonin, that

492
00:46:41,410 --> 00:46:47,450
it would just confuse the matter. At that
point I realised that I was on my own because

493
00:46:47,450 --> 00:46:53,180
if I couldn’t confess to my doctor that
I was taking melatonin, how could I confess

494
00:46:53,180 --> 00:47:00,180
to her that I was taking chloroquine and (*) and
other pharmaceuticals. I didn’t add all

495
00:47:00,720 --> 00:47:07,720
the ingredients at once. I added them incrementally.
I basically included any ingredient, be it

496
00:47:12,089 --> 00:47:18,400
a supplement or a pharmaceutical that was
active against cancer and didn’t interfere

497
00:47:18,400 --> 00:47:25,400
with the other ingredients. The pharmaceuticals
had to be dosed correctly, and the dosage

498
00:47:25,440 --> 00:47:32,440
I used was that carried out in the research
paper on cancer that I found. You have to

499
00:47:33,730 --> 00:47:40,569
read very closely these articles to get the
correct dosage – but it’s there.

500
00:47:40,569 --> 00:47:46,200
At its peak his cocktail numbered over 25
different components, and in order to access

501
00:47:46,200 --> 00:47:52,089
them all, Rich broke every rule in the book:
From feigning symptoms of other ailments in

502
00:47:52,089 --> 00:47:57,690
order to access non-cancer drugs that he believed
may also act against his disease, to forging

503
00:47:57,690 --> 00:47:59,250
prescriptions.

504
00:47:59,250 --> 00:48:06,250
There were moments during my cocktail therapy
when I thought I was doing too much, and I

505
00:48:07,599 --> 00:48:14,599
was getting out of my own comfort zone which
is nothing like medicine, but, I realised

506
00:48:17,839 --> 00:48:24,839
that the alternatives were very small: either
I tried something much more radical than the

507
00:48:26,710 --> 00:48:33,630
standard of care, or I would die. And when
you’re faced with that kind of decision,

508
00:48:33,630 --> 00:48:37,970
why not use more ingredients?

509
00:48:37,970 --> 00:48:44,240
Long term survivors of malignant brain tumours
are extremely rare. What makes Ben and Rich

510
00:48:44,240 --> 00:48:49,960
even more unusual amongst this tiny data group,
is that they have never had a recurrence - their

511
00:48:49,960 --> 00:48:54,829
cancer has never come back.

512
00:48:54,829 --> 00:49:01,089
A glioblastoma can’t really be cured. Never.
I never think about cure and I don’t talk

513
00:49:01,089 --> 00:49:08,089
to anybody about cure. I think that every
year that you live without a recurrence is

514
00:49:08,640 --> 00:49:15,640
great. I think Ben Williams now has lived
eighteen years without a recurrence if I’m

515
00:49:17,720 --> 00:49:22,960
not mistaken. I’ve lived six and a half
years without a recurrence. At that point

516
00:49:22,960 --> 00:49:28,809
you can say that we’re under control, but
you can’t say that we’re cured because

517
00:49:28,809 --> 00:49:35,809
there is always a possibility that it could
come back.

518
00:49:36,589 --> 00:49:40,109
Ethics in question

519
00:49:40,109 --> 00:49:44,880
After the horrors of the human experimentation
that characterised the holocaust, at the Nuremberg

520
00:49:44,880 --> 00:49:49,750
trials the international community laid down
the founding principals of a clinicians ethical

521
00:49:49,750 --> 00:49:55,540
obligation, initially referred to as the Nuremberg
code and later ratified in the Declaration

522
00:49:55,540 --> 00:50:01,309
of Geneva as an extension of the Hippocratic
Oath. Building upon these foundations, the

523
00:50:01,309 --> 00:50:07,000
world of medicine unilaterally subscribed
to the Declaration of Helsinki in 1964, and

524
00:50:07,000 --> 00:50:12,770
its primary revision in 1975 that introduced
the principal of ethical review by an independent

525
00:50:12,770 --> 00:50:19,359
committee. In doing so, the global medical
community enshrined the moral truth that ‘concern

526
00:50:19,359 --> 00:50:26,359
for the interests of the subject must always
prevail over the interests of science and

527
00:50:26,660 --> 00:50:30,430
society’. Can we honestly say that today’s
double-blind studies on terminal cancer patients

528
00:50:30,430 --> 00:50:32,540
adhere to this principal?

529
00:50:32,540 --> 00:50:39,540
Frankly, that I don’t know how a neuro-oncologist
could go home and look themselves in the mirror

530
00:50:41,030 --> 00:50:48,030
at night given what he knows and the outcome
of his patients are. I just don’t think

531
00:50:49,900 --> 00:50:55,079
it’s even ethical. I wouldn’t be able
to live just presiding over patients, just

532
00:50:55,079 --> 00:51:00,150
giving them radiation and chemotherapy and
at the same time, knowing that they are all

533
00:51:00,150 --> 00:51:02,270
going to die.

534
00:51:02,270 --> 00:51:07,890
I think the general concern in the oncology
community is that this is a terminal disease

535
00:51:07,890 --> 00:51:12,049
and when diagnosed with a GBM you are going
to die. I think that philosophy is kind of

536
00:51:12,049 --> 00:51:16,869
counterproductive to doing anything meaningful,
so I think our goal is to put patients on

537
00:51:16,869 --> 00:51:21,869
clinical trials to press the field forward,
but when you can’t do that, to do something

538
00:51:21,869 --> 00:51:24,589
better than a standard of care which is palliative.

539
00:51:24,589 --> 00:51:31,589
What we are fighting against is the negligence
that physicians are not aiming to inform themselves,

540
00:51:33,020 --> 00:51:36,880
that they are not forming an opinion themselves.

541
00:51:36,880 --> 00:51:41,540
If you face this disease and say from the
get go that this it is incurable - you will

542
00:51:41,540 --> 00:51:45,690
always be right, all your patients will die
and you have no business treating those patients

543
00:51:45,690 --> 00:51:47,540
in the first place.

544
00:51:47,540 --> 00:51:54,540
I think it is one of the toughest situations
in everyday clinical work. This is a point

545
00:51:56,099 --> 00:52:03,099
where it is really necessary to really explore
the patient’s wishes and really find out

546
00:52:04,369 --> 00:52:11,369
if the patient is willing to take an additional
risk for a chance, for a possibility of having

547
00:52:14,940 --> 00:52:21,940
a better (*). The problem is that a patient
who is asked to take an additional risk for

548
00:52:23,700 --> 00:52:28,319
a chance to survive will almost always say
yes.

549
00:52:28,319 --> 00:52:34,540
So the central issue is the question of protecting
patients rights at both ends of the spectrum:

550
00:52:34,540 --> 00:52:38,849
whilst uninformed vulnerable patients need
protection from unreasonable offers of experimental

551
00:52:38,849 --> 00:52:44,400
therapy at one end, equally should patients
at the opposite end of the spectrum, who do

552
00:52:44,400 --> 00:52:49,410
not wish to accept a palliative standard of
care, be denied the right to fight for their

553
00:52:49,410 --> 00:52:54,240
lives? When their doctors refuse to co-operate,
these patients inevitably find themselves

554
00:52:54,240 --> 00:53:00,049
outside of the medical system. We wondered
how many other cancer patients have embarked

555
00:53:00,049 --> 00:53:06,589
into unchartered territory of self-medication,
without their story ever coming to light.

556
00:53:06,589 --> 00:53:11,540
In California, we heard of another desperate
struggle against terminal cancer. But for

557
00:53:11,540 --> 00:53:17,770
Neil and Margo Hutchison, there was no happy
ending. neuroblastoma, a rare cancer of the

558
00:53:17,770 --> 00:53:23,470
nervous system, claimed the life of their
eldest son Sam aged just 8 years old.

559
00:53:23,470 --> 00:53:29,319
He was a very active little kid. Loved sports,
loved anything with balls, loved trucks, he

560
00:53:29,319 --> 00:53:36,319
ran like the wind, we was a funny, great fantastic
kid. When he was four and a half we were at

561
00:53:37,589 --> 00:53:41,250
a soccer game and he sat down and said ‘my
legs hurt’, and he always used to jump out

562
00:53:41,250 --> 00:53:45,589
of our van and he started to sit down to get
out of our van so we that something was definitely

563
00:53:45,589 --> 00:53:51,260
wrong. We decided to get some blood tests
and an X-ray and he was diagnosed with neuroblastoma.

564
00:53:51,260 --> 00:53:57,170
55:38 N: Sam began one of heaviest chemotherapy
regimens used in medicine with accompanying

565
00:53:57,170 --> 00:54:01,290
stem cell transplant that meant he lost his
hearing and would be sterile for the rest

566
00:54:01,290 --> 00:54:07,109
of his life. But with such a high grade of
malignancy Neil and Margo were told Sam had

567
00:54:07,109 --> 00:54:09,150
very little chance of surviving.

568
00:54:09,150 --> 00:54:16,150
Well first off, I mean, you’re shocked,
I mean, I think even parents of someone diagnosed

569
00:54:17,410 --> 00:54:21,040
with paediatric leukaemia would just, you
know, – it has a very high survival rate

570
00:54:21,040 --> 00:54:25,549
– you know, it still it punches you in the
gut, but when they sit you down…

571
00:54:25,549 --> 00:54:32,079
You’re just… yeah, you’re in shock for
months.

572
00:54:32,079 --> 00:54:36,369
After the shock dissipates, the dislocation
between the patient’s perspective and that

573
00:54:36,369 --> 00:54:41,910
of their medical teams was a common factor
in all the cases we covered during filming.

574
00:54:41,910 --> 00:54:45,540
It is clear that while the Hutchison's have
both a deep respect and appreciation for the

575
00:54:45,540 --> 00:54:50,780
doctors who treated their son, they had also
come up against the same compassionate fatalism

576
00:54:50,780 --> 00:54:54,619
that proved so unpalatable to Ben Williams
and Richard Gerber.

577
00:54:54,619 --> 00:54:57,990
I think that one argument that we used to
have with doctors when we talked about issues

578
00:54:57,990 --> 00:55:03,390
like this is, they’d say… I’d say like
‘hey listen, throw the book at these kids,

579
00:55:03,390 --> 00:55:08,430
it’s non toxic, get them in there, throw
cocktails at them and see how they do.’

580
00:55:08,430 --> 00:55:12,289
Their argument back to me would be like well,
‘if some child survives we don’t know

581
00:55:12,289 --> 00:55:16,680
why’, and I’d say ‘yeah, but that’s
a medical, scientific perspective. From a

582
00:55:16,680 --> 00:55:21,869
parent perspective we don’t care why. He’s
alive and we’ll figure it out’. If we

583
00:55:21,869 --> 00:55:25,760
keep doing it we’ll figure it out. We’ll
back door the answer. Somehow, someway, some

584
00:55:25,760 --> 00:55:29,710
shape or form. The scientific community wants
to know why.

585
00:55:29,710 --> 00:55:34,720
They believe in what they’re doing and,
know you, they want something that’s science

586
00:55:34,720 --> 00:55:38,619
based. They want a clinical trial. They want
the proven results. That takes years to get

587
00:55:38,619 --> 00:55:40,329
that kind of data, and these kids don’t
have that kind of time.

588
00:55:40,329 --> 00:55:46,130
And you’d see the data, you’d see child
after child die and you’d have that mental

589
00:55:46,130 --> 00:55:49,250
calculus going in your mind all the time because
you don’t want to harm your kid either because

590
00:55:49,250 --> 00:55:52,200
the Hippocratic Oath is apparent: First do
no harm. It’s not about that…

591
00:55:52,200 --> 00:55:56,079
Right, and so it’s not like you’re making
crazy, uneducated, you know, ‘we’re just

592
00:55:56,079 --> 00:55:57,250
going to try anything’ decisions but…

593
00:55:57,250 --> 00:56:02,680
You are absolutely right but like okay, but
I know this outcome. I don’t know what this

594
00:56:02,680 --> 00:56:05,619
is going to be, but I know where this is going.

595
00:56:05,619 --> 00:56:12,119
Given that the probability that the patient
is going to die is astronomical – it’s

596
00:56:12,119 --> 00:56:19,119
almost 100% – what harm is there is adding
other ingredients to the therapy?

597
00:56:20,400 --> 00:56:25,829
Why on earth would you possibly oppose it?
And the only answer to that is well, that’s

598
00:56:25,829 --> 00:56:29,539
not part of the standard care and we’re
afraid that if you use anything other than

599
00:56:29,539 --> 00:56:33,839
the standard of care that somehow we’ll
make things worse in a way that we don’t

600
00:56:33,839 --> 00:56:37,079
understand. That’s not an acceptable position
in my view.

601
00:56:37,079 --> 00:56:44,079
For the vast majority of patients, it is also
an unacceptable position. The advent of the

602
00:56:44,329 --> 00:56:49,680
internet has seen a growing underground network
of patients and carers supporting each other.

603
00:56:49,680 --> 00:56:52,809
This film is a direct result of such a community.

604
00:56:52,809 --> 00:56:59,809
We had, you know, the whole community of neuroblastoma
parents who were medical doctors and things

605
00:57:00,240 --> 00:57:04,000
themselves, and what we tried to do was read
the preclinical data, you know, and we were

606
00:57:04,000 --> 00:57:07,609
just trying to stay ahead of the curve and
kind of predict where things were going to

607
00:57:07,609 --> 00:57:11,910
go clinically. You know, you see a single
agent clinical trial and you know the data

608
00:57:11,910 --> 00:57:15,819
for that or you talk to – it might not be
published data – but because we are neuroblastoma

609
00:57:15,819 --> 00:57:20,700
community we know that 10 kids are on it and
they all progressed. There’d be publish,

610
00:57:20,700 --> 00:57:24,480
preclinical data saying that ‘hey, the next
trial that’s going to come up is going to

611
00:57:24,480 --> 00:57:29,400
be adding this second drug’, and so we would
get the second drug, and that was very common

612
00:57:29,400 --> 00:57:30,819
place.

613
00:57:30,819 --> 00:57:35,670
High profile survivors like Ben and Rich find
themselves inundated with requests for their

614
00:57:35,670 --> 00:57:41,420
advice, and having experienced the despair
of falling outside the medical system themselves,

615
00:57:41,420 --> 00:57:45,890
they can appreciate the desperation of patients
with no where to left to turn.

616
00:57:45,890 --> 00:57:52,099
I’m an engineer, and many engineers carry
out risk benefit analysis naturally and routinely

617
00:57:52,099 --> 00:57:58,670
in their work. In terms of the cocktails that
I had identified, I did my own independent

618
00:57:58,670 --> 00:58:04,579
research, evaluated what the potential benefits
were compared to the side effects, and it

619
00:58:04,579 --> 00:58:07,890
was quite clearly something that ought to
be tried. With the benefit of hindsight and

620
00:58:07,890 --> 00:58:09,079
the reflection of where I am relative to the
prognosis, I am concerned that this approach

621
00:58:09,079 --> 00:58:11,859
could not have taken place sooner. Many of
the doctors feel that they are not able to

622
00:58:11,859 --> 00:58:18,859
engage in these off plan treatments, and perhaps
those that are outside the normal sphere of

623
00:58:19,410 --> 00:58:24,859
training because they tend to feel that the
Hippocratic Oath limits their ability to do

624
00:58:24,859 --> 00:58:30,809
that in the principle of ‘do no harm’.
But I believe that there are equally sins

625
00:58:30,809 --> 00:58:37,809
of omission as there are 
of commission.

626
00:59:01,849 --> 00:59:04,789
There is no doubt that in the future we’re
going to be looking at multiple therapies.

627
00:59:04,789 --> 00:59:11,789
The question that arises: doesn’t the patient
have the right to go an pursue combination

628
00:59:11,940 --> 00:59:17,819
therapies and put them all together in a way
they think and their doctors hope will facilitate

629
00:59:17,819 --> 00:59:23,680
a long term cure? The problem again comes
back to the issue of toxicity. Unless you

630
00:59:23,680 --> 00:59:29,710
carefully study these combination therapies,
you may be doing more harm than good in many

631
00:59:29,710 --> 00:59:35,670
cases, and although that there is clearly
the impetus to move forward with combination

632
00:59:35,670 --> 00:59:38,510
therapies, they need to be studied.

633
00:59:38,510 --> 00:59:43,549
However, for the reasons outlined in this
film, there is a distinct lack of clinical

634
00:59:43,549 --> 00:59:48,760
trials investigating a cocktail approach to
cancer. Instead, it is normal practice to

635
00:59:48,760 --> 00:59:53,630
expect patients to forgo curative treatment
in the hope that their sacrifice will someday

636
00:59:53,630 --> 00:59:55,900
benefit someone else in their same position.

637
00:59:55,900 --> 01:00:01,720
If you go to a major medical centre where
they are doing clinical trials, the trials

638
01:00:01,720 --> 01:00:08,140
are not really a hundred percent intended
for the patient, they’d be intended for

639
01:00:08,140 --> 01:00:15,140
a future patient, it’s intended for science
- or for a drug company - but, it’s intended

640
01:00:15,400 --> 01:00:21,140
to find out more about the drug, it’s not
intended to cure the patient. Patients are

641
01:00:21,140 --> 01:00:28,140
not aware of that. For science it is important
to study things singly because otherwise it’s

642
01:00:30,680 --> 01:00:37,039
confounding. We cannot deal with multiple
unknown variables. You throw five drugs that

643
01:00:37,039 --> 01:00:40,950
we don’t know much about t somebody and
they get better, we don’t really know what

644
01:00:40,950 --> 01:00:46,400
happened. Which one of A, B, C, D, E did it?
We don’t know. You want to find out how

645
01:00:46,400 --> 01:00:51,539
a drug works… that’s in scientific spirit.
That’s great for science, but there is some

646
01:00:51,539 --> 01:00:56,900
conflict with clinical care which is with
a different intention: you want the patient

647
01:00:56,900 --> 01:00:58,049
to get better.

648
01:00:58,049 --> 01:01:03,589
When looked at closely, the history of cancer
tells its own story: In another era, when

649
01:01:03,589 --> 01:01:07,539
doctors were more empowered to pursue patient
survival as a primary objective of clinical

650
01:01:07,539 --> 01:01:13,480
care, dramatic progress was achieved in a
relatively short period of time. One such

651
01:01:13,480 --> 01:01:18,539
doctor whose belief system is entirely geared
to patient outcome was a young haematologist

652
01:01:18,539 --> 01:01:25,390
working at the newly formed National Cancer
Institute in the early 1960s. Emil J Freireich

653
01:01:25,390 --> 01:01:29,920
was certain he had figured out a way to send
leukaemia into permanent remission. But he

654
01:01:29,920 --> 01:01:34,530
faced enormous resistance for attempting to
combine highly toxic chemotherapy agents.

655
01:01:34,530 --> 01:01:41,530
When I started treating leukaemia - I have
a slide of a quote from an article that was

656
01:01:41,849 --> 01:01:47,970
written by a guy named Arthur Haut, who was
one of the senior physicians at the number

657
01:01:47,970 --> 01:01:53,920
one haematology department in the world in
1955 when I went to the cancer institute.

658
01:01:53,920 --> 01:02:00,740
The quote says… just what you said: giving
these drugs , 6MP, methotrexate, prednisone

659
01:02:00,740 --> 01:02:07,740
to these children is just prolonging their
suffering, it has no effect on their survival.

660
01:02:10,220 --> 01:02:14,880
And he was on our consultant (panel) and he
told our advisors that Freireich should no

661
01:02:14,880 --> 01:02:19,480
be allowed to poison these dying children
–to let them die.

662
01:02:19,480 --> 01:02:24,670
Undeterred by fierce resistance from his professional
community, Freireich questionably pushed ahead

663
01:02:24,670 --> 01:02:30,799
with the assistance of some desperate parents,
and the rest is history. Today, a giant in

664
01:02:30,799 --> 01:02:35,559
the field of oncology after blazing the trail
towards cure for childhood leukaemia, and

665
01:02:35,559 --> 01:02:42,190
in the process inventing the platelet transfusion,
at the age of 87 Dr Emil J Freireich has half

666
01:02:42,190 --> 01:02:46,380
a century of outstanding achievement in clinical
practice to reflect upon.

667
01:02:46,380 --> 01:02:53,380
See I’m a devotee of the Hippocratic Oath.
That’s why it’s on my wall. Every physician

668
01:02:54,569 --> 01:03:00,480
in the United States, and I think in England
and in Europe, who graduates from his medical

669
01:03:00,480 --> 01:03:07,190
training swears by the Hippocratic Oath. Now
what’s the essence of the Hippocratic Oath?

670
01:03:07,190 --> 01:03:14,190
Now what’s the essence of Hippocratic Oath
is that, as a physician, I will always do

671
01:03:14,869 --> 01:03:21,390
whatever I can to help a person who is ill
and consults me.

672
01:03:21,390 --> 01:03:26,329
For cancer patients staring death in the face,
the chilling realisation that despite a palliative

673
01:03:26,329 --> 01:03:29,940
standard of care, they must wait for their
cancer to inevitably progress before their

674
01:03:29,940 --> 01:03:36,940
doctors will engage with experimental treatments,
defies belief. In the vast majority of cases,

675
01:03:37,130 --> 01:03:42,700
only then do experimental treatment options
become available to patients. We asked Dr

676
01:03:42,700 --> 01:03:46,650
Freireich if in his opinion, this broke the
Hippocratic Oath…

677
01:03:46,650 --> 01:03:53,650
It certainly does. Is there ever a circumstance
where a patient should be denied treatment

678
01:03:57,730 --> 01:04:04,730
which could – in someone’s imagination
– help him survive his disease? And the

679
01:04:04,809 --> 01:04:07,200
answer is no.

680
01:04:07,200 --> 01:04:11,220
System Failure

681
01:04:11,220 --> 01:04:18,220
Would the things we did in 1960 be possible
in today? The answer is, unequivocally, capital

682
01:04:19,329 --> 01:04:23,010
‘N’, capital ‘O’ – NO!

683
01:04:23,010 --> 01:04:28,020
By obliging doctors to follow rigid protocols,
our system for validating cancer treatments

684
01:04:28,020 --> 01:04:32,329
is not only failing patients, but it is also
failing the innovators who are developing

685
01:04:32,329 --> 01:04:38,480
treatments: a hidden consequence of forcing
patients to wait for cancer to reoccur before

686
01:04:38,480 --> 01:04:43,490
giving them access to experimental treatments,
is that potentially promising treatments are

687
01:04:43,490 --> 01:04:48,450
first tested only on these ‘recurrent’
patient populations, who already have genetically

688
01:04:48,450 --> 01:04:53,380
mature cancer, and thus are far less likely
to respond to the drug or treatment than an

689
01:04:53,380 --> 01:04:59,730
early stage patient. This means potentially
life-extending treatments for the newly diagnosed

690
01:04:59,730 --> 01:05:05,559
are discarded forever because they cannot
show effect first on moribund patients.

691
01:05:05,559 --> 01:05:12,500
Reforming regulations is the most important
thing we can do in advancing health in the

692
01:05:12,500 --> 01:05:19,500
world. The AIDS patients told us how to solve
societal problems for specific diseases. See,

693
01:05:20,890 --> 01:05:25,980
the AIDS guys were homosexuals and they were
used to being politically active and they

694
01:05:25,980 --> 01:05:31,760
were organised, and when the FDA said you
have to do a randomised trial where you get

695
01:05:31,760 --> 01:05:37,140
treatment you know won’t work and compare
it to treatment you think will work… they

696
01:05:37,140 --> 01:05:44,140
said ‘hell no!’ and they marched on the
hill and they won. My personal view is that

697
01:05:45,480 --> 01:05:50,799
that’s the way medical problems should be
solved. First we need the knowledge, then

698
01:05:50,799 --> 01:05:53,599
we need the social solution.

699
01:05:53,599 --> 01:05:59,170
ACT UP - the AIDS coalition to unleash power
- was a direct action group widely credited

700
01:05:59,170 --> 01:06:03,799
with instigating the rapid acceleration of
AIDS research that transformed the once deadly

701
01:06:03,799 --> 01:06:09,930
virus to a chronic condition in little over
a decade. Larry Kramer, New York City playwright

702
01:06:09,930 --> 01:06:15,700
and author was a founding member, speaking
in the late 1980s as the AIDS pandemic gripped

703
01:06:15,700 --> 01:06:21,329
the world in the face of institutional and
political indifference, his words echo violently

704
01:06:21,329 --> 01:06:27,900
in the ears of cancer patients today: ‘placebo
studies were not designed with terminal illness

705
01:06:27,900 --> 01:06:34,400
in mind’ he said and the ‘academic mechanism
of testing drugs is becoming life-threatening

706
01:06:34,400 --> 01:06:41,400
rather than life-saving’, it’s ‘genocide
by neglect’ he claimed. As a result of ACT

707
01:06:41,400 --> 01:06:46,839
UP’s unprecedented lobbying of congress
and the FDA, which included emptying urns

708
01:06:46,839 --> 01:06:51,680
onto the white house lawn as per the will
of their members’, today’s life saving

709
01:06:51,680 --> 01:06:55,349
treatment for AIDS is given to patient’s
despite it never having passed a randomised

710
01:06:55,349 --> 01:07:02,349
phase three clinical trial: How many cancer
patients must die before the regulators recognise

711
01:07:03,579 --> 01:07:07,190
this needs to be adapted to oncology in the
same fashion?

712
01:07:07,190 --> 01:07:14,190
All they have to learn to do is balance benefits
against risks. If you have nine drugs that

713
01:07:14,910 --> 01:07:19,750
are going to cure glioblastoma and you have
a patient that is 100% likely to die… lets

714
01:07:19,750 --> 01:07:26,529
give them the nine drugs! Who’s against
that? You can’t do anything risk free. That

715
01:07:26,529 --> 01:07:33,529
does not exist. You can’t walk across the
street without taking a chance. You can’t

716
01:07:34,230 --> 01:07:41,230
wake up in the morning, you can’t eat food.
I mean, it’s nice to do as well as you can,

717
01:07:41,640 --> 01:07:45,859
but you can’t be insane and we are insane
now. The regulatory process is insane. They

718
01:07:45,859 --> 01:07:52,740
are trying to protect people. They inadvertently
get into a situation where they kill people…

719
01:07:52,740 --> 01:07:57,940
but that’s not their intent. We’re just
human unfortunately.

720
01:07:57,940 --> 01:08:03,400
For patients and carers, once these inefficiencies
come into focus, the incentive to adhere to

721
01:08:03,400 --> 01:08:07,960
the rules of clinical trials evaporates along
with the validity of the precious data the

722
01:08:07,960 --> 01:08:08,789
trial produces.

723
01:08:08,789 --> 01:08:15,710
Do you want me to be totally honest? Yeah,
sure, neuroblastoma patients ship drugs. We’d

724
01:08:15,710 --> 01:08:21,540
ship drugs by fed ex. We’d find clinical
trials and we’d be on a single agent and

725
01:08:21,540 --> 01:08:26,410
we’d – other parents on the other trial
would send us their drugs and we’d send

726
01:08:26,410 --> 01:08:33,390
our drugs. We had viruses from Israel that
other parents had given us that we’d tried

727
01:08:33,390 --> 01:08:38,520
and… that’s what we did. There’s a whole
black market and grey market of drugs because

728
01:08:38,520 --> 01:08:44,040
parents are so knowledgeable. I mean, there’s
Doctors, PHDs, MDs that have children with

729
01:08:44,040 --> 01:08:47,910
neuroblastoma and it’s a very tight community
and they would do anything for anybody. In

730
01:08:47,910 --> 01:08:54,910
fact, we, you know - that’s what we did
- created our own clinical trials for the

731
01:08:55,500 --> 01:08:57,160
most part.

732
01:08:57,160 --> 01:09:01,750
In randomised phase 3 trials, you have the
additional disincentive of placebo control

733
01:09:01,750 --> 01:09:07,649
for half the patients. A quick glance at the
appalling enrolment rates around the world

734
01:09:07,649 --> 01:09:10,609
and we can see that patient’s vote with
their feet.

735
01:09:10,609 --> 01:09:17,609
It’s so obvious that if the FDA allowed
us to be rational about treating cancer patients,

736
01:09:18,830 --> 01:09:25,310
we could move them all one hundred times faster.
As we did with AIDS, because what happened

737
01:09:25,310 --> 01:09:29,910
was, the drug was good and the patients didn’t
have to die to prove it. And as you said in

738
01:09:29,910 --> 01:09:32,850
the beginning ‘you need to do a randomised
phase 3 clinical trial’ No! if you have

739
01:09:32,850 --> 01:09:38,500
phase two evidence that’s clear, if you
have an objective response, objective survival,

740
01:09:38,500 --> 01:09:45,500
objective progression free survival, that’s
it… The truth is in itself. You don’t

741
01:09:48,040 --> 01:09:52,500
have to do comparison, you have to have the
truth, you have to have reproducibility, you

742
01:09:52,500 --> 01:09:58,120
have to have a lack of bias, and what you’ve
got there… that’s the answer man! The

743
01:09:58,120 --> 01:10:05,120
AIDS guys did it. The cancer patients have
to do it. We have to force congress to change

744
01:10:05,120 --> 01:10:11,680
legislation so that when a doctor and a patient
agree that the benefits succeed the potential

745
01:10:11,680 --> 01:10:18,680
risk… that should go. Whatever way we make
it, that’s got to go.

746
01:10:20,320 --> 01:10:22,390
New horizons

747
01:10:22,390 --> 01:10:29,390
In all of the clinical trials to date, there
really hasn’t been much progress. Meanwhile,

748
01:10:30,700 --> 01:10:36,410
those people however are dying. Yes, people
live a little bit longer with the standard

749
01:10:36,410 --> 01:10:42,540
approach that we have now, but it’s not
much. And so, I would say this approach is

750
01:10:42,540 --> 01:10:46,240
not working. It’s time to try something
else.

751
01:10:46,240 --> 01:10:52,830
Traditionally, regulatory bodies have made
decisions that have been based on population

752
01:10:52,830 --> 01:10:59,660
studies. So if you think about it for a moment…
We introduce a drug into a large population

753
01:10:59,660 --> 01:11:04,680
in which we know there are many variables
in that population - people are different

754
01:11:04,680 --> 01:11:10,780
– and we can’t control for those variables,
we don’t know what they are sometimes, we

755
01:11:10,780 --> 01:11:17,390
just know they exist. So the way we dealt
with that in the past was to create this statistical

756
01:11:17,390 --> 01:11:24,390
model of randomisation and, in fact, blinded
randomisation so we cover our eyes, and we

757
01:11:26,390 --> 01:11:33,390
flip a coin, and we divide people up, and
we look for an outcome, and when we get an

758
01:11:33,640 --> 01:11:40,640
outcome we put a statistical number on it,
and that gives us some assurance that yes,

759
01:11:41,890 --> 01:11:48,890
that was really due to the drug and not something
else. Do we need that today? If I could go

760
01:11:49,700 --> 01:11:56,700
into that population and I could - today - tell
you about those variables - which I couldn’t

761
01:11:58,210 --> 01:12:05,210
before - because now I understand those genetic,
molecular make up of their individual cancer,

762
01:12:07,220 --> 01:12:14,220
and I also under stand their genetic molecular
make up of them, as a person, and now I can

763
01:12:14,360 --> 01:12:20,330
refine those populations. Do I still need
to put a blindfold on and flip a coin? Or

764
01:12:20,330 --> 01:12:27,140
can I begin to be much more rational about
who I would treat with a particular drug and

765
01:12:27,140 --> 01:12:34,130
who I would not. That is the adaptive trial
design. That is what cancer is teaching us

766
01:12:34,130 --> 01:12:40,550
and telling us what we can now do, so we don’t
need to depend upon that old model. We can

767
01:12:40,550 --> 01:12:47,550
be much more sophisticated, much more rational,
and we will get answers faster, we’ll be

768
01:12:48,750 --> 01:12:55,750
much more certain that our answer is in fact
correct, and we will be able to allow patients

769
01:12:56,810 --> 01:13:03,810
to have access to lifesaving drugs quicker,
faster, and with more assurance that they

770
01:13:04,140 --> 01:13:07,350
are going to help them and not hurt them.

771
01:13:07,350 --> 01:13:11,860
We accompanied Ben to University of California
Moore’s Cancer Centre to meet one of a new

772
01:13:11,860 --> 01:13:16,320
generation of oncologists engaged in an ambitious
program of personalized medicine...

773
01:13:16,320 --> 01:13:22,590
There’s two issues. One is, you know, what
are the best combinations for each particular

774
01:13:22,590 --> 01:13:27,400
patient? Because, I think we all know that
glioblastoma is a different disease in every

775
01:13:27,400 --> 01:13:31,540
single patient. If you took a hundred people
in a room there’s probably fifty diseases,

776
01:13:31,540 --> 01:13:38,300
and so what we’re finding is that single
drugs seem to work better in some patients

777
01:13:38,300 --> 01:13:43,120
than others because of the genetic make-up
of the tumour, and so when you talk about

778
01:13:43,120 --> 01:13:47,820
combinations it’s even more complicated.
But we actually have a project where we’re

779
01:13:47,820 --> 01:13:52,130
taking all the genetic information from each
patient, putting it into a computer, and coming

780
01:13:52,130 --> 01:13:56,590
up with an answer to what drugs would be most
effective to each patient. So, it’s really

781
01:13:56,590 --> 01:14:02,450
a personalised medicine approach to understanding
the genetics and using that information to

782
01:14:02,450 --> 01:14:04,600
find the best combinations.

783
01:14:04,600 --> 01:14:09,450
So as we move towards personalised medicine
where patients will receive combinations of

784
01:14:09,450 --> 01:14:13,860
treatments, and that these combinations should
reflect the genetic characteristics of different

785
01:14:13,860 --> 01:14:18,810
patients, then the only logical conclusion
to be drawn is that until we dismantle the

786
01:14:18,810 --> 01:14:23,920
sanctity reserved for large-scale, randomised
phase III trials, we will never see meaningful

787
01:14:23,920 --> 01:14:26,810
changes in patient survival.

788
01:14:26,810 --> 01:14:33,090
Personalised medicine is the mantra. The irony
is that the practices up to now are directly

789
01:14:33,090 --> 01:14:39,270
opposed to doing it. You can not – for most
of the randomised trials that are done, even

790
01:14:39,270 --> 01:14:45,010
though you get a significant result – tell
an individual patient what the chances of

791
01:14:45,010 --> 01:14:51,090
that treatment working for them will be. Right,
I mean, so, if you can’t do that, what you

792
01:14:51,090 --> 01:14:55,980
started out… I mean the purpose of what
you started out to do - you’ve failed. You

793
01:14:55,980 --> 01:15:02,520
need more homogeneous patients so that you
can actually say for this group of fairly

794
01:15:02,520 --> 01:15:07,520
similar patients this particular treatment
will work. Well, you’re never going to do

795
01:15:07,520 --> 01:15:13,100
randomised trials once you start thinking
in that framework of needing homogeneous patients.

796
01:15:13,100 --> 01:15:19,200
Well if we don’t change the regulatory process,
what we’re already seeing is the biomedical

797
01:15:19,200 --> 01:15:26,200
research enterprises collapsing. We’re seeing
investments beginning to dwindle because quite

798
01:15:28,410 --> 01:15:35,410
frankly if you’re a venture capitalist or
an equity investor, you have far safer, quicker

799
01:15:36,700 --> 01:15:43,700
opportunities for a return on investment than
to engage in hoping that a molecule - that

800
01:15:44,270 --> 01:15:48,750
you’re going to be willing to fund very
early in it’s development – some how or

801
01:15:48,750 --> 01:15:55,750
other is going to make its way through a 10-15
year process at the cost of over a billion

802
01:15:57,410 --> 01:16:04,410
dollars to ultimately be able to give you
a return on that investment. So we’re seeing

803
01:16:04,810 --> 01:16:10,850
negative consequences of not doing something,
and at the same time we also have the realisation

804
01:16:10,850 --> 01:16:17,560
of the incredible opportunities if we would
do something and therefore, change has to

805
01:16:17,560 --> 01:16:20,050
occur.

806
01:16:20,050 --> 01:16:22,540
Acceleration

807
01:16:22,540 --> 01:16:28,540
At the current rate of development of combination
therapy, testing combinations one by one,

808
01:16:28,540 --> 01:16:32,600
it will take decades, and possibly centuries
to deliver more expansive cocktails to the

809
01:16:32,600 --> 01:16:38,620
clinic. In the face of a clinical trial system
that is clearly failing, a new line of thought

810
01:16:38,620 --> 01:16:44,540
is gaining traction in some oncology circles.
One man who is not hiding behind protocol,

811
01:16:44,540 --> 01:16:49,870
is Marc Halatsch. He founded the International
Initiative for the Acceleration of Glioblastoma

812
01:16:49,870 --> 01:16:55,390
Care as a framework to combine expertise and
engineer a treatment he feels will have a

813
01:16:55,390 --> 01:17:00,600
better chance of combating cancer’s genetic
instability. This radical work involving untested

814
01:17:00,600 --> 01:17:05,700
drug cocktails does not sit comfortably within
his scientific community, nor the pharmaceutical

815
01:17:05,700 --> 01:17:08,840
companies Marc would normally enjoy sponsorship
from.

816
01:17:08,840 --> 01:17:15,840
We have to (*) the protocol and that initially
involved 17 drugs. All of these drugs were

817
01:17:17,010 --> 01:17:24,010
chosen to act in (*) against glioblastoma
to inhibit or suffocate signalling pathways

818
01:17:24,920 --> 01:17:31,920
that are important for glioblastoma. We consciously
avoided to identify new targets for the glioblastoma

819
01:17:33,910 --> 01:17:40,910
treatment. We were referring to drugs that
are approved are marketed for years for other

820
01:17:41,400 --> 01:17:47,770
non-oncological indications and for which
a reasonable safety profile is already available.

821
01:17:47,770 --> 01:17:54,770
So, the accelerated improvement means that
we are using drugs, that we want to use drugs

822
01:17:56,100 --> 01:18:00,760
that are already available today, for which
we already have experience with human use

823
01:18:00,760 --> 01:18:07,440
rather than identifying a new molecular target
and validating a candidate track for years

824
01:18:07,440 --> 01:18:13,240
and years and then possibly finding out that
it doesn’t work. We have a rational basis

825
01:18:13,240 --> 01:18:19,910
that these compounds are effective, that they
can be effective, and that they have reasonable

826
01:18:19,910 --> 01:18:25,850
and justifiable risks even though we do not
know how these risks adapt when these substances

827
01:18:25,850 --> 01:18:26,920
are combined.

828
01:18:26,920 --> 01:18:32,300
During filming we were contacted by a senior
drug researcher for Glaxo-Smith-Klein in Cambridge

829
01:18:32,300 --> 01:18:38,450
England, who had been diagnosed himself with
a high grade, inoperable brain tumour. He

830
01:18:38,450 --> 01:18:44,350
refused to come on camera, even with his identity
hidden, but he was interested in Marc’s

831
01:18:44,350 --> 01:18:49,680
paper, referring to the science behind it
as ‘beautiful’. But when he travelled

832
01:18:49,680 --> 01:18:53,800
to a major centre for brain cancer in London,
in the hope of finding a forward thinking

833
01:18:53,800 --> 01:19:00,800
clinician who might prescribe him the experimental
protocol, he was told the study was ‘unscientific’.

834
01:19:01,850 --> 01:19:06,600
He died in 2014 leaving three young children.

835
01:19:06,600 --> 01:19:13,600
Well if people say the paper is unscientific…
I think that it’s a judgement that cannot

836
01:19:16,430 --> 01:19:23,430
be accepted because the paper is certainly
not unscientific. It is making a proposal

837
01:19:23,560 --> 01:19:30,560
based on a set of hypothesis, and all of these
hypothesis are based on preclinical data,

838
01:19:30,690 --> 01:19:37,690
on what we think is robust preclinical data.
What we can say for sure is that the recent

839
01:19:39,230 --> 01:19:45,380
architecture of medical research for glioblastoma
patients has failed to bring out substantial

840
01:19:45,380 --> 01:19:51,750
improvements for these patients and we don’t
know if you can do it better, but… we want

841
01:19:51,750 --> 01:19:54,410
to try.

842
01:19:54,410 --> 01:19:58,320
It is no coincidence that cancer cocktails
are first coming to light in the arena of

843
01:19:58,320 --> 01:20:03,920
brain cancer. The limitations of surgical
intervention in the brain provide the impetus.

844
01:20:03,920 --> 01:20:10,200
There’s a shift going on right now in a
lot of oncology where you may want to biopsy

845
01:20:10,200 --> 01:20:17,200
a cancer, treat for four weeks with a mono
therapy (one drug), re-biopsy that cancer,

846
01:20:17,410 --> 01:20:23,600
see if the genetics have changed, treat again
with a different drug for some period of time…

847
01:20:23,600 --> 01:20:28,720
and so as the cancer shifts and mutates, you’re
changing your therapy accordingly.

848
01:20:28,720 --> 01:20:33,430
If you don’t do that you may be treating
according to a profile that is simple outdated

849
01:20:33,430 --> 01:20:38,230
because a tumour is a dynamic. The biological
situation may already have changed.

850
01:20:38,230 --> 01:20:43,010
Now we can’t biopsy like that in the brain.
You can do that in the lung, the breast and

851
01:20:43,010 --> 01:20:48,330
other answers… bone marrow. So we have to
figure out how’ll overcome those genetic

852
01:20:48,330 --> 01:20:50,580
changes that will occur with treatment.

853
01:20:50,580 --> 01:20:57,580
Well I believe, in the absence of bio-marker
profiles, it is very important to have a pragmatic

854
01:20:58,980 --> 01:21:05,980
approach and to hit multiple targets at once
so that even if there is a change in the profile

855
01:21:08,930 --> 01:21:15,270
and some pathways may compensate for other
inhibited pathways, you have a high chance

856
01:21:15,270 --> 01:21:22,040
of maintaining a higher therapeutic pressure
against the tumour. In general, multi agent

857
01:21:22,040 --> 01:21:27,980
protocol can be defended by pointing out the
heterogeneity of the tumour, and if you have

858
01:21:27,980 --> 01:21:34,190
a set of drugs that act in concert then you
have a simple rule, and the rule is, the more

859
01:21:34,190 --> 01:21:40,680
drugs you have the better you probably will
be able to address heterogeneity of the tumour.

860
01:21:40,680 --> 01:21:45,670
This is an example of the new rational science
of treating cancer, based on the lessons that

861
01:21:45,670 --> 01:21:50,810
cancer itself is teaching us. Yet what Marc
and his peers are pioneering, is in reality

862
01:21:50,810 --> 01:21:56,710
revolutionary. The pharmaceutical companies
that own the drugs he is using have refused

863
01:21:56,710 --> 01:22:01,000
financial support for his research, and he
is risking his professional reputation in

864
01:22:01,000 --> 01:22:06,680
medical circles by even publishing this paper.
Cocktails are considered radical because if

865
01:22:06,680 --> 01:22:11,620
such an ‘unscientific’ approach were to
work for patients, it would equate to opening

866
01:22:11,620 --> 01:22:15,860
Pandora’s box, with the associated danger
of patients no longer being willing to accept

867
01:22:15,860 --> 01:22:21,800
current medical practices. Few oncologists
would be willing to support such an investigation,

868
01:22:21,800 --> 01:22:25,680
John Boockvar in New York, was an exception.

869
01:22:25,680 --> 01:22:32,680
The idea of carpet bombing a cancer is an
appropriate idea where you just bombard the

870
01:22:35,230 --> 01:22:40,260
tumour with multiple agents that will come
at it from different signalling pathways,

871
01:22:40,260 --> 01:22:47,200
much like they do with HIV medicines, and
it will take that kind of approach to see

872
01:22:47,200 --> 01:22:53,200
– I think – good outcomes. Of course our
delivery mechanisms, our ability to get these

873
01:22:53,200 --> 01:23:00,200
drugs into tumours has to be better, our immune
systems in these patients has to be augmented,

874
01:23:01,540 --> 01:23:08,540
improvement in immunotherapy will be an important
adjunct to any treatment, because if we cant

875
01:23:08,750 --> 01:23:14,050
identify mutating cells or cells that are
distinct you have no chance… because chemotherapy

876
01:23:14,050 --> 01:23:20,790
is only going to do so much without destroying
the natural body.

877
01:23:20,790 --> 01:23:25,330
Never say die

878
01:23:25,330 --> 01:23:30,030
Of all the patients we met during filming,
one man’s story stood out for his exceptional

879
01:23:30,030 --> 01:23:35,300
courage and determination in the face of imminent
death. Anders Ferry is still fighting his

880
01:23:35,300 --> 01:23:41,600
disease today, 15 years after being diagnosed
with terminal cancer at the age of 32. His

881
01:23:41,600 --> 01:23:47,230
remarkable struggle for survival has encompassed
6 recurrences and 5 neurosurgeries including

882
01:23:47,230 --> 01:23:53,400
some ground-breaking therapies and interventions.
Unable to travel alone, Anders and his father

883
01:23:53,400 --> 01:23:58,140
Arne travelled to London at their own cost
from the far north of Sweden, to share his

884
01:23:58,140 --> 01:23:59,260
story in this film.

885
01:23:59,260 --> 01:24:06,070
Well I have been experimenting with my own
body and taking various odd combinations of

886
01:24:06,070 --> 01:24:13,070
medications and non-mediations as well, under
very uncontrolled circumstances. So this has

887
01:24:13,860 --> 01:24:20,860
been a marathon for me and for my wife in
particular. She has seen me through extremely

888
01:24:23,020 --> 01:24:29,840
low points. The low points have been really
low, close to death.

889
01:24:29,840 --> 01:24:34,890
Ander’s original course of chemotherapy
was stopped due to the development of a severe

890
01:24:34,890 --> 01:24:39,940
rash, a result of sitting in a sauna trying
to raise his body temperature in order to

891
01:24:39,940 --> 01:24:45,330
increase the efficacy of the chemotherapy,
Anders claims this rash released him from

892
01:24:45,330 --> 01:24:50,190
a chemo educed mental-fog and afforded him
the clarity to do some preliminary research

893
01:24:50,190 --> 01:24:55,900
online. He immediately enrolled on an innovative
American trial for an early immunological

894
01:24:55,900 --> 01:25:00,880
compound. However, the compound was unapproved
in Europe at the time, so he had to smuggle

895
01:25:00,880 --> 01:25:04,500
the drugs through customs as battery electrolytes.

896
01:25:04,500 --> 01:25:09,770
So I was doing very well on that treatment,
but then after a couple of years they said

897
01:25:09,770 --> 01:25:16,770
‘now we’re dropping the trial. Unfortunately
you won’t get anymore drug.’ And I panicked

898
01:25:18,290 --> 01:25:24,040
of course. I thought, well this is what has
been keeping me alive for so long so I immediately

899
01:25:24,040 --> 01:25:31,040
went into action to try to manufacture it
myself. As a physicist and physical chemist,

900
01:25:31,060 --> 01:25:37,290
it wouldn’t be difficult for me to actually
create that molecule in the lab. So I pulled

901
01:25:37,290 --> 01:25:42,450
all the patents and bought the chemicals,
borrowed lab resources, and my mother volunteered

902
01:25:42,450 --> 01:25:47,140
to be my guinea pig to try it first before
I injected it myself.

903
01:25:47,140 --> 01:25:51,810
At the eleventh hour, the founder of the drug
company, who had got wind of Anders’ desperate

904
01:25:51,810 --> 01:25:57,730
attempt to stay on the medication, called
and insisted he did not use his own acetate,

905
01:25:57,730 --> 01:26:02,930
instead sending him a life-time supply of
the drug the next day. By this time, it was

906
01:26:02,930 --> 01:26:06,860
becoming clear to Anders that this was just
the beginning of his struggle, and that the

907
01:26:06,860 --> 01:26:09,660
next challenge lay in combining different
treatments.

908
01:26:09,660 --> 01:26:16,660
Well I got the idea to do several things simultaneously
when I read Ben Williams’ thoughts on it.

909
01:26:19,940 --> 01:26:26,940
So I started adding little drugs that I could
access, gradually building up to a protocol

910
01:26:30,730 --> 01:26:37,730
that involved many drugs in a big drug cocktail.
At its peak I was taking at least 8 prescription

911
01:26:41,340 --> 01:26:48,340
drugs – off label… of course, they were
not chemotherapies, but assigned for entirely

912
01:26:51,960 --> 01:26:58,960
different diagnosis – and lots of nutraceuticals.
The biggest obstacle to implement this protocol

913
01:27:01,470 --> 01:27:08,110
has always been to actually find the prescription
drugs. They are available but you need somebody

914
01:27:08,110 --> 01:27:14,120
to write the prescription, and I have been
lucky to have relatives and close friends

915
01:27:14,120 --> 01:27:21,120
that could manage that for me. Sticking their
necks out. And occasionally my treating oncologist

916
01:27:25,930 --> 01:27:32,930
has written out a few, but very reluctantly,
and has always been questioning ‘but why?

917
01:27:34,550 --> 01:27:41,550
Is there any evidence for this?’ And I said
‘no, but there’s a potential in it.

918
01:27:45,460 --> 01:27:52,460
Evidence is weak but there is some kind of hope. 
Let’s try it, I’m willing.’ As the alternative

919
01:27:53,320 --> 01:28:00,320
of doing nothing, you just look at the statistics…
every body dies within two years they said.

920
01:28:00,430 --> 01:28:07,430
Well that’s not acceptable. By doing something
proactively, possibly ruining your health,

921
01:28:10,960 --> 01:28:17,960
getting terrible side effects, but also possibly
getting real benefits, extending life. Like

922
01:28:21,320 --> 01:28:28,320
I’m here now, a decade and a half later,
I’ve got two little kids, a happy wife,

923
01:28:28,560 --> 01:28:34,200
a beautiful wife. My little Lynae and Tim
they are just my pride and joy of my life.

924
01:28:34,200 --> 01:28:41,200
So, it has worked out well for me. Sure I
have deficits, but I can live with that. Life

925
01:28:44,270 --> 01:28:47,820
with deficits is still life.

926
01:28:47,820 --> 01:28:52,300
On three separate occasions, Anders has fought
back his cancer by combining conventional

927
01:28:52,300 --> 01:28:57,770
surgery with innovative clinical trials, and
extensive, specifically tailored cocktails

928
01:28:57,770 --> 01:28:59,840
of off-label drugs and nutraceuticals.

929
01:28:59,840 --> 01:29:06,840
Well concerning the oncologists, I said ‘I’m
not really satisfied’ because when Anders

930
01:29:08,520 --> 01:29:15,520
has his medication and it didn’t work and
the protocol didn’t work, they said ‘sorry

931
01:29:15,630 --> 01:29:22,630
we can’t do anymore. You go home and play
with your girl’. I put the question, who

932
01:29:26,940 --> 01:29:33,940
is responsible for their lives? Is it my son
who is supposed to take the care in his hand,

933
01:29:40,480 --> 01:29:47,480
or is it so that the oncologist must have
some responsibility? He just can’t hide

934
01:29:49,330 --> 01:29:51,360
behind the protocols.

935
01:29:51,360 --> 01:29:56,610
Ander’s fight is one that is far from over,
and yet he too spends a great deal of his

936
01:29:56,610 --> 01:30:01,650
time advising other patients, sharing whatever
knowledge or contacts he may have.

937
01:30:01,650 --> 01:30:07,970
So ever since I created my internet persona
– Andrew Yassin – and hit the internet,

938
01:30:07,970 --> 01:30:14,970
I’ve seen so many people come and go on
the lists. It’s terrible. Many people of

939
01:30:16,950 --> 01:30:23,950
whom I’ve connected so strongly to, just
pass away. It’s dreadful.

940
01:30:26,120 --> 01:30:33,120
Do you think that those patients were denied
something?

941
01:30:37,490 --> 01:30:44,490
Absolutely, they were absolutely denied the
best care that could have been provided. I’m

942
01:30:45,720 --> 01:30:50,510
sure many more would have been alive – or
at least had a much better chance to be alive

943
01:30:50,510 --> 01:30:57,510
– if they had access to what I have been
doing for instance. I am also sure that this

944
01:30:58,190 --> 01:31:05,190
approach could apply to other cancers, not
only brain tumours. I’ve seen effect in

945
01:31:06,690 --> 01:31:13,690
advanced prostate cancers and breast cancers.
If I create a prescription of various off-label

946
01:31:14,860 --> 01:31:21,860
drugs there is a viable option of prolonging
life for a long time, and that is also including

947
01:31:25,800 --> 01:31:32,800
a creative and active life. I play my trumpet
at international jazz festivals. Perhaps not

948
01:31:34,470 --> 01:31:41,470
at the same level as I could before having
all the surgeries, but still… it is a life

949
01:31:42,080 --> 01:31:49,080
I enjoy and the kind I’m of proud of so
I’ve done well.

950
01:31:53,350 --> 01:31:54,690
Reflections

951
01:31:54,690 --> 01:31:59,300
Already facing a terminal diagnosis, should
cancer patients have to shoulder the additional

952
01:31:59,300 --> 01:32:04,870
terror of unsupervised self-medication in
search of a meaningful attempt at survival?

953
01:32:04,870 --> 01:32:09,720
None of the patients we spoke to wanted to
go it alone, they desperately wanted the reassurance

954
01:32:09,720 --> 01:32:14,900
of professional medical supervision. Their
courage has showed us that the impossible

955
01:32:14,900 --> 01:32:19,860
is sometimes possible, that there could be
a solution to problems we perceive as beyond

956
01:32:19,860 --> 01:32:20,990
our reach.

957
01:32:20,990 --> 01:32:27,990
I believe the medical community has an obligation
to do research into the cause – the clinical

958
01:32:31,080 --> 01:32:38,080
cause of patients who have undertaken self-medications,
and who have reported extended life-span with

959
01:32:40,710 --> 01:32:46,380
glioblastoma. I think it is an ethical obligation
of the medical community to try to understand

960
01:32:46,380 --> 01:32:51,260
what happened with these patients, how they
did it, what their quality of life was and

961
01:32:51,260 --> 01:32:54,380
how long they survived - these patients cannot
be ignored.

962
01:32:54,380 --> 01:33:01,380
As survivors today, patients like Ben, Rich
and Anders stand as proof of principal. We

963
01:33:01,570 --> 01:33:06,110
have the unprecedented opportunity to follow
this lead, employing the gifts that science

964
01:33:06,110 --> 01:33:13,110
and technology are affording us to actively
embrace change. In the era of big data, Google,

965
01:33:13,340 --> 01:33:18,340
and Apple, society can rationally ask the
medical establishment to reconsider its confidence

966
01:33:18,340 --> 01:33:23,830
in a regulatory structure that served us well
in the past, but that appears slow, inefficient

967
01:33:23,830 --> 01:33:30,830
and even inhumane in the context of terminal
disease today. The quid pro quo, that can

968
01:33:31,510 --> 01:33:36,940
secure the continuation of a scientific methodology
and rational development of therapies, can

969
01:33:36,940 --> 01:33:43,940
be the clinical data from EVERY patient. Retrospective
analysis of this data in the era of genomics,

970
01:33:44,460 --> 01:33:48,810
can deliver the precious information we are
searching for in clinical trials, faster,

971
01:33:48,810 --> 01:33:51,050
cheaper and more accurately.

972
01:33:51,050 --> 01:33:58,050
Every professional I have ever talked to,
every oncologist, every neuro-oncologist,

973
01:34:00,660 --> 01:34:07,660
every radio oncologist I’ve talked to, believes
that I am a freak chance, that my tumour would

974
01:34:08,730 --> 01:34:15,730
have been put under control anyway, and that
my cocktail therapy didn’t contribute one

975
01:34:18,050 --> 01:34:25,050
iota to it. They also think that Ben Williams
is a freak chance and that his 18 years would

976
01:34:27,230 --> 01:34:34,230
have been given to him even without his experimentation,
and anybody that lives a long time – longer

977
01:34:35,380 --> 01:34:42,380
than average - and uses a cocktail approach
is similarly dismissed as a freak chance.

978
01:34:44,570 --> 01:34:51,570
But at a certain point, people are going to
have to start looking at the evidence.

979
01:34:53,110 --> 01:34:58,400
Some will dismiss this evidence as merely
exceptions that prove the rule. But it is

980
01:34:58,400 --> 01:35:04,080
hard to dismiss as coincidence Ben, Rich and
Anders’ shared academic background and scientific

981
01:35:04,080 --> 01:35:10,290
training, unusual or illegal access to prescription
drugs, and the determination to overcome all

982
01:35:10,290 --> 01:35:14,560
obstacles in the pursuit of their unorthodox
cancer therapies.

983
01:35:14,560 --> 01:35:21,560
I’m quite sure that if I hadn't done what
I did I wouldn't be alive today. If I had

984
01:35:22,190 --> 01:35:29,190
simply followed the prescription of my neuro-oncologist
I would have been just another statistic,

985
01:35:30,380 --> 01:35:37,380
namely I would have lived another 12-18 months
and that would have been it. Because to my

986
01:35:37,400 --> 01:35:39,630
knowledge he never had another long term survivor...

987
01:35:39,630 --> 01:35:40,230
'Insanity is doing the same thing over and
over again, and expecting a different result'

988
01:35:40,230 --> 01:35:40,480
– Albert Einstein

989
01:35:40,310 --> 01:35:40,910
The Repurposing of Drugs in Oncology is an
initiative to provide oncologists with a robust,

990
01:35:40,910 --> 01:35:41,470
independently researched database of old drugs
that could be helpful to combine with existing

991
01:35:41,470 --> 01:35:42,030
standards of care across all cancers, enabling
them to prescribe off-label drugs with confidence

992
01:35:42,030 --> 01:35:42,350
they will help and not hurt their patients.

993
01:35:42,350 --> 01:35:43,330
With the support of a small charity in Belgium,
Marc Halatsch and Richard Kast’s CUSP9 cocktail

994
01:35:43,330 --> 01:35:44,930
of drugs is in final stages of approval in
Germany for a phase 1 clinical trial for recurrent

995
01:35:44,930 --> 01:35:46,170
glioblastoma. If the German regulatory authority
approve this trial in spring 2015 as anticipated,

996
01:35:46,170 --> 01:35:47,150
they will set a global precedent for other
regulators to follow.

997
01:35:47,150 --> 01:35:48,570
The film makers, together with the patients
and some of the doctors featured in this film,

998
01:35:48,570 --> 01:35:55,270
are working with a UK charity to open an international
phase 1 clinical trial to investigate an expansive

999
01:35:55,270 --> 01:36:00,750
cocktail approach for the newly diagnosed,
as an adjuvant therapy to the standard of

1000
01:36:00,750 --> 01:36:07,400
care for Glioblastoma. It remains to be seen
how such a proposal will be received by the

1001
01:36:07,400 --> 01:36:09,350
regulatory authorities across the world…

1002
01:36:09,350 --> 01:36:16,000
However, even if these trials go ahead, it
will take vast sums of money and many years

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01:36:16,000 --> 01:36:22,650
to ascertain if they hold benefit for patients.
Closing The Gap Now is an initiative to demonstrate

1004
01:36:22,650 --> 01:36:27,740
consensus within the scientific community
that patients with a prognosis of less than

1005
01:36:27,740 --> 01:36:33,000
24 months should be allowed access to any
treatment with phase 1 approval, in return

1006
01:36:33,000 --> 01:36:34,980
for donating their clinical data to an open-access
research database. The scientific community

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01:36:34,980 --> 01:36:37,280
would then be able to obtain certainty about
which treatments work for which patients much

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01:36:37,280 --> 01:36:43,730
faster, cheaper and more accurately than the
current system allows. www.closingthegapnow.org

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01:36:43,730 --> 01:36:50,730
For brain tumour patients who wish to view
extended interviews from this film please

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01:36:54,480 --> 01:36:56,020
visit www.virtualtrials.com