Surviving Terminal Cancer

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

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

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

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

Congress, 1971

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

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

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

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

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

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

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

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

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

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

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

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

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

have built for testing cancer treatments?

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

think that a mountain of evidence is being
over looked.

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

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

in the first place.

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

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

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

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

treatments’ … but I decided otherwise.

Surviving Terminal Cancer

The Everest of oncology

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

biological heterogeneity demands therapeutic
heterogeneity: or more simply brain cancer

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

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

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

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

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

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

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

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

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

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

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

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

today, could revolutionise the treatment of
all cancers tomorrow.

‘A round trip to Hades’

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

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

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

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

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

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

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

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

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

respected survivor and patient advocate.

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

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

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

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

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

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

way to describe it.

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

treatment available to him would not save
his life.

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

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

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

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

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

how to make that as easy a process as possible.

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

radiation and chemotherapy.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

evidence.

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

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

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

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

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

right about the idea that they were worth
trying.

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

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

of patients lack.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

use everything that was available.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

treatments.

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

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

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

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

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

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

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

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

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

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

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

to face in his body.

Logic Dictates

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

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

Bullet poses an uncomfortable question for
the oncology community.

Oncology thinking somewhat followed infectious
disease treatment thinking because the first

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

properly.

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

treatments that delivered the breakthrough.
Today infectious disease treatments follow

this logic.

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

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

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

practitioners.

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

oncology community.

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

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

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

therapy.

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

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

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

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

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

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

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

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

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

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

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

could just get further, faster?

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

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

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

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

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

was a step in the right direction.

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

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

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

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

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

Simple, simple drugs.

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

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

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

issue.

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

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

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

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

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

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

treatment.

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

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

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

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

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

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

uncertainties about the risks involved.

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

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

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

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

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

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

Resistance

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

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

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

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

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

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

by patient.

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

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

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

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

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

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

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

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

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

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

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

at the moment, it becomes more and more difficult.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

are testament to the holistic vision behind
the Texan project.

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

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

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

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

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

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

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

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

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

safe, it shouldn’t hurt them in any way.
Second is the efficacy. There is no third

rule, and curcumin meets both of them.

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

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

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

is there any evidence to support this claim.

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

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

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

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

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

gene or single protein - a single target disease.
By now, we are living in the era of ‘omics’:

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

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

and their mind is set on targeted therapies.
They want a targeted therapy, if it is not

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

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

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

Dr Aggarwal, anything you do with respect
to natural products I don’t believe even

one bit of it. They don’t even want to read…
and we publish in the same journals. We are

most highly cited. People don’t want to
read. There’s this, you know, in born bias.

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

and they don’t their patients have any leeway
in making a decision that sort of kind of

moves them in the direction of alternative
medicine. It’s a real concern on their part.

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

kooky guys who goes around trying to throw
out anything under the sun into your treatment

protocol.

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

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

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

was persecuted for his acknowledgement of
Copernicus’ theory and his pursuit of a

new rational science in its wake. Even Gallileo’s
presentation of his new invention, the telescope

and it’s irrefutable new evidence, could
not dampen the fervour of his condemnation.

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

in the venerated hospitals of Vienna at its
empirical peek, noticed an alarming correlation

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

and babies in the maternity wards of those
same hospitals. His suggestion that perhaps

his fellow surgeons should consider using
chlorine to wash hands before operating on

patients, was met with vicious resistance.
Unable to substantiate his theory scientifically,

Semmelweis was ostracised professionally by
his peers for daring to question the status

quo. He died 15 years later in a mental institution,
a broken man, yet a century and a half later

he is venerated as a national hero in Hungary,
where statues and coins carry his legacy as

the father of sterile medicine. Today, the
Semmelweis reflex is a term used to describe

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

- the Semmelweis reflex is alive and well
in today’s medical establishment: Barry

Marshall, a little known doctor from Western
Australia, had identified a bacteria in the

early 1980s that indicated stomach ulcers
were caused by bacteria. This was heresy to

the established thinking in the field of endoscopy,
which was convinced that stomach ulcers were

caused by stress. As a result Marshall’s
thesis was not published in any medical journals

and sat on the shelves gathering dust while
hundreds of thousands of patients across the

world had their stomachs removed, unnecessarily
so according to his theory. With the bacteria

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

successful animal experiments that the medical
establishment deemed pre-requisite for Marshall

to progress to human trials, could thus never
be completed. So locked out of both animal

and human experimentation, but convinced of
his theory, Marshall chose to experiment on

the one human he did have legal access to:
himself. In front of an audience of stunned

peers, he downed a petri dish full of bacteria
grafted from a patients’ stomach, and claimed

to have infected himself with a stomach ulcer.
The proof duly came, as did his cure without

the need to remove his stomach, swiftly followed
by an avalanche of awards and praise from

the establishment, culminating with the Nobel
Prize in 2005. Beyond the more obscure issue

of medical hegemony, lie more obvious reasons
for why combination therapies do not reach

patients.

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

company C, it is extremely difficult to get
all three of those drug companies together

to agree to use their drugs to treat a particular
disease process. It’s much easier if the

drugs all come from one company… and that
is a fundamental challenge that not just neurosurgical

patients with glioblastoma face, but all cancer
patients face. And from the company stand

point one could make a good argument that
it’s reasonable and understandable that

this is the case because they invest hundreds
of millions, sometimes billions of dollars

to develop that drug, and as that drug comes
to market it goes to the FDA, the application

of that drug to other disease processes in
combination with other drugs could cause a

lot of problems for them. So it’s a very
difficult thing to address.

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

be patented, for the very same reason, drugs
whose patent has expired are similarly discarded

as they cannot guarantee a return on the investment
required to run a clinical trial. This results

in a large number of drugs with strong laboratory
evidence for anticancer properties never getting

anywhere near patients. In some cases, even
when human trials have been run it is still

not enough to bring the drug into the mainstream
treatment.

A very nice example is the use of the old
malaria drug which is dirt cheap, Chloroquine,

for brain cancer where nice trials have been
carried out showing improvements up to 50%

survival time when it’s added to standard
chemotherapy. It has almost no side effects.

It’s one pill a day. It does not mean the
patient has to suffer going to the hospital,

get a drip, any of this. It’s dirt cheap.
Why not? Well, FDA has not approved its use

for this condition - for one. The information
is not widely disseminated. There’s no big

drug company behind the manufacture of chloroquine
to market it for this use. Nobody makes much

money if suddenly every brain cancer patient
starting taking chloroquine, it adds very

little to the bottom line of any particular
business or company.

So it is more and more important for us to
look at these drugs that have been left on

the shelf, that big pharma wants nothing to
do with, but we don’t initially have the

time or the resources to provide the data
managers, the IRB fees and start up fees that

it takes run a good clinical trial.

Aside from the influence of the medical world
status quo, and the economic reasons hampering

development of combination therapies for cancer,
there is a strong feeling amongst the patients

we interviewed as to why oncologists are unwilling
to deviate from established best practices,

even in the context of terminal disease.

One of the problems from a patient’s perspective
is that they want as many drugs as possible

to facilitate long tern survival, and that’s
a very reasonable request from the stand point

of a patient. If you have cancer, you hear
a certain drug might be effective in your

particular type of cancer, you want to access
that drug. You hear that another type of drug

might be effective, you want to actually just
go ahead and combine those drugs, and so fourth

and so on. From a patient’s perspective,
you are entitled to pursue any type of therapy

you want to. From a provider’s perspective,
from a neurosurgeon, a scientist, from a a

neurosurgical oncologist’s perspective,
we have to be very, very careful about what

we recommend to patients in terms of going
after therapies that are unproven.

Doctors are judged by so-called standards
of practice in the community. So, if in California

this is the way we do things, here, in LA,
this is the was we do things… and you do

it differently and the patient gets hurt,
and you’re in court, they will summon your

peers and say well, how do you do things usually?
And every body says ‘I don’t use Temodar,

I don’t do Temodar + chloroquine

This issue of liability is one of the silent
enemies in the war on cancer. Drs and hospitals

who would willingly take more risks for their
patients who have run out of options, are

discouraged from doing so by fear of malpractices
suits. This fear of prosecution is not limited

to doctors, but runs deep through the entire
system, dissuading individuals and teams from

doing anything outside of the box for their
patients.

The specialists are at major cancer institutions
that does not treat patients as individual

unlike what patients may think. They treat
as a group. They can call it a team approach,

but they treat by committee, literally there
is a committee of doctors who review cases

– it’s called a tumour board – and almost,
you can imagine, 6,7 specialists at the centre

every week, sit down and go over new cases
and decide ‘this is what we’re going to

do.’ Now, that also creates an issue because
then everybody has to agree for one, then

of course what everybody agrees on in any
bureaucratic structure has to be the lowest

common denominator. Okay? But that’s the
safest way for the doctors and the hospital

because if there was a problem, and if the
was a charge, they say well, ‘six specialists

had a committee meeting on the same week – and
we all agreed… you want to sue six of us?

And we represent the hospital are you going
to sue the whole hospital for this decision?

every one of our patients get exactly the
same thing. What’s wrong with this? We are

following the guide lines from the American
cancer society’. So, everything is therefore

protected, protected, protected… for liability
reasons. So it’s fool proof. If you try

to be individualistic, stick your neck out,
give chloroquine because there’s a paper

that says give chloroquine, and something
goes wrong, you don’t have anything backing

you up in the court of law. It’s much safer
to follow a protocol. A protocol is one thing

at a time until it’s proven otherwise. The
proof may never come because there is no funding

to try to prove these things. Who gains from
proving them? Who is going to fund the proving

of this? These are much larger issues that
I think will hamper developments of true cocktails

unless there is radical changes in health
care systems and social systems. It may not

come.…

Lightening doesn’t strike twice

Ben's Williams book is nothing more than a
blueprint for anyone who wants to follow a

more pro-active approach to their own treatment.
One such patient was Richard Gerber, a fellow

American academic living in Italy, who was
diagnosed with the same lethal brain tumour

a decade after Ben. Given just months to live,
Rich had nothing to lose.

During the chemotherapy and radiotherapy that
I had – although it was very exhausting

– I started reading at night, articles and
journals, and I realised that therapy was

not going to really make my life any longer
so I started doing research into alternatives,

and little by little, on the internet, I came
across this name ‘Ben Williams’ who had

written a book. I ordered the book. And it
basically is teaching people to take their

matters into their own hands and to be their
own doctors in part. So far, this cocktail

approach that he writes about in his book
has proved efficacious for me. I wasn’t

just blindly following Ben. In fact, I wouldn’t
have followed Ben at all if his arguments

weren’t logically convincing.

In common with Ben, Rich shared a scientific
background, he is an expert at developing

solutions for complex problems.

I took what we call a ‘black box’ concept
that is glioblastoma is a very, very complicated

phenomenon. Nobody knows: how it works, how
it grows, how it gets started, how the therapy

works, and papers are published on very specific
subjects and very specific genetic pathways,

but there is no integration of this information.
So, my approach was based on finding as many

agents which could block assorted pathways
which activate glioblastoma, and doing it

all at once so that the glioblastoma would
have less of a chance to mutate and escape

via a path way because I would already be
blocking that pathway.

Of course, assembling and consuming an unsupervised
and untested cocktail of drugs and neutraceuticals

is daunting even for someone with an in depth
appreciation of their disease. One of the

patients we interviewed equated it to playing
Russian roulette whilst on death row.

My doctor was a very sympathetic oncologist,
but she was very ‘by the book’. She didn’t

want me to do anything else. Coming up with
my own notions I suggested to this doctor

that I would like to take melatonin. I tossed
this out as sort of a test because at the

time I was actually taking 10 or 15 other
pharmaceuticals but I thought I would start

small and she didn’t want to hear about
it. She told me not to take melatonin, that

it would just confuse the matter. At that
point I realised that I was on my own because

if I couldn’t confess to my doctor that
I was taking melatonin, how could I confess

to her that I was taking chloroquine and (*) and
other pharmaceuticals. I didn’t add all

the ingredients at once. I added them incrementally.
I basically included any ingredient, be it

a supplement or a pharmaceutical that was
active against cancer and didn’t interfere

with the other ingredients. The pharmaceuticals
had to be dosed correctly, and the dosage

I used was that carried out in the research
paper on cancer that I found. You have to

read very closely these articles to get the
correct dosage – but it’s there.

At its peak his cocktail numbered over 25
different components, and in order to access

them all, Rich broke every rule in the book:
From feigning symptoms of other ailments in

order to access non-cancer drugs that he believed
may also act against his disease, to forging

prescriptions.

There were moments during my cocktail therapy
when I thought I was doing too much, and I

was getting out of my own comfort zone which
is nothing like medicine, but, I realised

that the alternatives were very small: either
I tried something much more radical than the

standard of care, or I would die. And when
you’re faced with that kind of decision,

why not use more ingredients?

Long term survivors of malignant brain tumours
are extremely rare. What makes Ben and Rich

even more unusual amongst this tiny data group,
is that they have never had a recurrence - their

cancer has never come back.

A glioblastoma can’t really be cured. Never.
I never think about cure and I don’t talk

to anybody about cure. I think that every
year that you live without a recurrence is

great. I think Ben Williams now has lived
eighteen years without a recurrence if I’m

not mistaken. I’ve lived six and a half
years without a recurrence. At that point

you can say that we’re under control, but
you can’t say that we’re cured because

there is always a possibility that it could
come back.

Ethics in question

After the horrors of the human experimentation
that characterised the holocaust, at the Nuremberg

trials the international community laid down
the founding principals of a clinicians ethical

obligation, initially referred to as the Nuremberg
code and later ratified in the Declaration

of Geneva as an extension of the Hippocratic
Oath. Building upon these foundations, the

world of medicine unilaterally subscribed
to the Declaration of Helsinki in 1964, and

its primary revision in 1975 that introduced
the principal of ethical review by an independent

committee. In doing so, the global medical
community enshrined the moral truth that ‘concern

for the interests of the subject must always
prevail over the interests of science and

society’. Can we honestly say that today’s
double-blind studies on terminal cancer patients

adhere to this principal?

Frankly, that I don’t know how a neuro-oncologist
could go home and look themselves in the mirror

at night given what he knows and the outcome
of his patients are. I just don’t think

it’s even ethical. I wouldn’t be able
to live just presiding over patients, just

giving them radiation and chemotherapy and
at the same time, knowing that they are all

going to die.

I think the general concern in the oncology
community is that this is a terminal disease

and when diagnosed with a GBM you are going
to die. I think that philosophy is kind of

counterproductive to doing anything meaningful,
so I think our goal is to put patients on

clinical trials to press the field forward,
but when you can’t do that, to do something

better than a standard of care which is palliative.

What we are fighting against is the negligence
that physicians are not aiming to inform themselves,

that they are not forming an opinion themselves.

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

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

in the first place.

I think it is one of the toughest situations
in everyday clinical work. This is a point

where it is really necessary to really explore
the patient’s wishes and really find out

if the patient is willing to take an additional
risk for a chance, for a possibility of having

a better (*). The problem is that a patient
who is asked to take an additional risk for

a chance to survive will almost always say
yes.

So the central issue is the question of protecting
patients rights at both ends of the spectrum:

whilst uninformed vulnerable patients need
protection from unreasonable offers of experimental

therapy at one end, equally should patients
at the opposite end of the spectrum, who do

not wish to accept a palliative standard of
care, be denied the right to fight for their

lives? When their doctors refuse to co-operate,
these patients inevitably find themselves

outside of the medical system. We wondered
how many other cancer patients have embarked

into unchartered territory of self-medication,
without their story ever coming to light.

In California, we heard of another desperate
struggle against terminal cancer. But for

Neil and Margo Hutchison, there was no happy
ending. neuroblastoma, a rare cancer of the

nervous system, claimed the life of their
eldest son Sam aged just 8 years old.

He was a very active little kid. Loved sports,
loved anything with balls, loved trucks, he

ran like the wind, we was a funny, great fantastic
kid. When he was four and a half we were at

a soccer game and he sat down and said ‘my
legs hurt’, and he always used to jump out

of our van and he started to sit down to get
out of our van so we that something was definitely

wrong. We decided to get some blood tests
and an X-ray and he was diagnosed with neuroblastoma.

55:38 N: Sam began one of heaviest chemotherapy
regimens used in medicine with accompanying

stem cell transplant that meant he lost his
hearing and would be sterile for the rest

of his life. But with such a high grade of
malignancy Neil and Margo were told Sam had

very little chance of surviving.

Well first off, I mean, you’re shocked,
I mean, I think even parents of someone diagnosed

with paediatric leukaemia would just, you
know, – it has a very high survival rate

– you know, it still it punches you in the
gut, but when they sit you down…

You’re just… yeah, you’re in shock for
months.

After the shock dissipates, the dislocation
between the patient’s perspective and that

of their medical teams was a common factor
in all the cases we covered during filming.

It is clear that while the Hutchison's have
both a deep respect and appreciation for the

doctors who treated their son, they had also
come up against the same compassionate fatalism

that proved so unpalatable to Ben Williams
and Richard Gerber.

I think that one argument that we used to
have with doctors when we talked about issues

like this is, they’d say… I’d say like
‘hey listen, throw the book at these kids,

it’s non toxic, get them in there, throw
cocktails at them and see how they do.’

Their argument back to me would be like well,
‘if some child survives we don’t know

why’, and I’d say ‘yeah, but that’s
a medical, scientific perspective. From a

parent perspective we don’t care why. He’s
alive and we’ll figure it out’. If we

keep doing it we’ll figure it out. We’ll
back door the answer. Somehow, someway, some

shape or form. The scientific community wants
to know why.

They believe in what they’re doing and,
know you, they want something that’s science

based. They want a clinical trial. They want
the proven results. That takes years to get

that kind of data, and these kids don’t
have that kind of time.

And you’d see the data, you’d see child
after child die and you’d have that mental

calculus going in your mind all the time because
you don’t want to harm your kid either because

the Hippocratic Oath is apparent: First do
no harm. It’s not about that…

Right, and so it’s not like you’re making
crazy, uneducated, you know, ‘we’re just

going to try anything’ decisions but…

You are absolutely right but like okay, but
I know this outcome. I don’t know what this

is going to be, but I know where this is going.

Given that the probability that the patient
is going to die is astronomical – it’s

almost 100% – what harm is there is adding
other ingredients to the therapy?

Why on earth would you possibly oppose it?
And the only answer to that is well, that’s

not part of the standard care and we’re
afraid that if you use anything other than

the standard of care that somehow we’ll
make things worse in a way that we don’t

understand. That’s not an acceptable position
in my view.

For the vast majority of patients, it is also
an unacceptable position. The advent of the

internet has seen a growing underground network
of patients and carers supporting each other.

This film is a direct result of such a community.

We had, you know, the whole community of neuroblastoma
parents who were medical doctors and things

themselves, and what we tried to do was read
the preclinical data, you know, and we were

just trying to stay ahead of the curve and
kind of predict where things were going to

go clinically. You know, you see a single
agent clinical trial and you know the data

for that or you talk to – it might not be
published data – but because we are neuroblastoma

community we know that 10 kids are on it and
they all progressed. There’d be publish,

preclinical data saying that ‘hey, the next
trial that’s going to come up is going to

be adding this second drug’, and so we would
get the second drug, and that was very common

place.

High profile survivors like Ben and Rich find
themselves inundated with requests for their

advice, and having experienced the despair
of falling outside the medical system themselves,

they can appreciate the desperation of patients
with no where to left to turn.

I’m an engineer, and many engineers carry
out risk benefit analysis naturally and routinely

in their work. In terms of the cocktails that
I had identified, I did my own independent

research, evaluated what the potential benefits
were compared to the side effects, and it

was quite clearly something that ought to
be tried. With the benefit of hindsight and

the reflection of where I am relative to the
prognosis, I am concerned that this approach

could not have taken place sooner. Many of
the doctors feel that they are not able to

engage in these off plan treatments, and perhaps
those that are outside the normal sphere of

training because they tend to feel that the
Hippocratic Oath limits their ability to do

that in the principle of ‘do no harm’.
But I believe that there are equally sins

of omission as there are
of commission.

There is no doubt that in the future we’re
going to be looking at multiple therapies.

The question that arises: doesn’t the patient
have the right to go an pursue combination

therapies and put them all together in a way
they think and their doctors hope will facilitate

a long term cure? The problem again comes
back to the issue of toxicity. Unless you

carefully study these combination therapies,
you may be doing more harm than good in many

cases, and although that there is clearly
the impetus to move forward with combination

therapies, they need to be studied.

However, for the reasons outlined in this
film, there is a distinct lack of clinical

trials investigating a cocktail approach to
cancer. Instead, it is normal practice to

expect patients to forgo curative treatment
in the hope that their sacrifice will someday

benefit someone else in their same position.

If you go to a major medical centre where
they are doing clinical trials, the trials

are not really a hundred percent intended
for the patient, they’d be intended for

a future patient, it’s intended for science
- or for a drug company - but, it’s intended

to find out more about the drug, it’s not
intended to cure the patient. Patients are

not aware of that. For science it is important
to study things singly because otherwise it’s

confounding. We cannot deal with multiple
unknown variables. You throw five drugs that

we don’t know much about t somebody and
they get better, we don’t really know what

happened. Which one of A, B, C, D, E did it?
We don’t know. You want to find out how

a drug works… that’s in scientific spirit.
That’s great for science, but there is some

conflict with clinical care which is with
a different intention: you want the patient

to get better.

When looked at closely, the history of cancer
tells its own story: In another era, when

doctors were more empowered to pursue patient
survival as a primary objective of clinical

care, dramatic progress was achieved in a
relatively short period of time. One such

doctor whose belief system is entirely geared
to patient outcome was a young haematologist

working at the newly formed National Cancer
Institute in the early 1960s. Emil J Freireich

was certain he had figured out a way to send
leukaemia into permanent remission. But he

faced enormous resistance for attempting to
combine highly toxic chemotherapy agents.

When I started treating leukaemia - I have
a slide of a quote from an article that was

written by a guy named Arthur Haut, who was
one of the senior physicians at the number

one haematology department in the world in
1955 when I went to the cancer institute.

The quote says… just what you said: giving
these drugs , 6MP, methotrexate, prednisone

to these children is just prolonging their
suffering, it has no effect on their survival.

And he was on our consultant (panel) and he
told our advisors that Freireich should no

be allowed to poison these dying children
–to let them die.

Undeterred by fierce resistance from his professional
community, Freireich questionably pushed ahead

with the assistance of some desperate parents,
and the rest is history. Today, a giant in

the field of oncology after blazing the trail
towards cure for childhood leukaemia, and

in the process inventing the platelet transfusion,
at the age of 87 Dr Emil J Freireich has half

a century of outstanding achievement in clinical
practice to reflect upon.

See I’m a devotee of the Hippocratic Oath.
That’s why it’s on my wall. Every physician

in the United States, and I think in England
and in Europe, who graduates from his medical

training swears by the Hippocratic Oath. Now
what’s the essence of the Hippocratic Oath?

Now what’s the essence of Hippocratic Oath
is that, as a physician, I will always do

whatever I can to help a person who is ill
and consults me.

For cancer patients staring death in the face,
the chilling realisation that despite a palliative

standard of care, they must wait for their
cancer to inevitably progress before their

doctors will engage with experimental treatments,
defies belief. In the vast majority of cases,

only then do experimental treatment options
become available to patients. We asked Dr

Freireich if in his opinion, this broke the
Hippocratic Oath…

It certainly does. Is there ever a circumstance
where a patient should be denied treatment

which could – in someone’s imagination
– help him survive his disease? And the

answer is no.

System Failure

Would the things we did in 1960 be possible
in today? The answer is, unequivocally, capital

‘N’, capital ‘O’ – NO!

By obliging doctors to follow rigid protocols,
our system for validating cancer treatments

is not only failing patients, but it is also
failing the innovators who are developing

treatments: a hidden consequence of forcing
patients to wait for cancer to reoccur before

giving them access to experimental treatments,
is that potentially promising treatments are

first tested only on these ‘recurrent’
patient populations, who already have genetically

mature cancer, and thus are far less likely
to respond to the drug or treatment than an

early stage patient. This means potentially
life-extending treatments for the newly diagnosed

are discarded forever because they cannot
show effect first on moribund patients.

Reforming regulations is the most important
thing we can do in advancing health in the

world. The AIDS patients told us how to solve
societal problems for specific diseases. See,

the AIDS guys were homosexuals and they were
used to being politically active and they

were organised, and when the FDA said you
have to do a randomised trial where you get

treatment you know won’t work and compare
it to treatment you think will work… they

said ‘hell no!’ and they marched on the
hill and they won. My personal view is that

that’s the way medical problems should be
solved. First we need the knowledge, then

we need the social solution.

ACT UP - the AIDS coalition to unleash power
- was a direct action group widely credited

with instigating the rapid acceleration of
AIDS research that transformed the once deadly

virus to a chronic condition in little over
a decade. Larry Kramer, New York City playwright

and author was a founding member, speaking
in the late 1980s as the AIDS pandemic gripped

the world in the face of institutional and
political indifference, his words echo violently

in the ears of cancer patients today: ‘placebo
studies were not designed with terminal illness

in mind’ he said and the ‘academic mechanism
of testing drugs is becoming life-threatening

rather than life-saving’, it’s ‘genocide
by neglect’ he claimed. As a result of ACT

UP’s unprecedented lobbying of congress
and the FDA, which included emptying urns

onto the white house lawn as per the will
of their members’, today’s life saving

treatment for AIDS is given to patient’s
despite it never having passed a randomised

phase three clinical trial: How many cancer
patients must die before the regulators recognise

this needs to be adapted to oncology in the
same fashion?

All they have to learn to do is balance benefits
against risks. If you have nine drugs that

are going to cure glioblastoma and you have
a patient that is 100% likely to die… lets

give them the nine drugs! Who’s against
that? You can’t do anything risk free. That

does not exist. You can’t walk across the
street without taking a chance. You can’t

wake up in the morning, you can’t eat food.
I mean, it’s nice to do as well as you can,

but you can’t be insane and we are insane
now. The regulatory process is insane. They

are trying to protect people. They inadvertently
get into a situation where they kill people…

but that’s not their intent. We’re just
human unfortunately.

For patients and carers, once these inefficiencies
come into focus, the incentive to adhere to

the rules of clinical trials evaporates along
with the validity of the precious data the

trial produces.

Do you want me to be totally honest? Yeah,
sure, neuroblastoma patients ship drugs. We’d

ship drugs by fed ex. We’d find clinical
trials and we’d be on a single agent and

we’d – other parents on the other trial
would send us their drugs and we’d send

our drugs. We had viruses from Israel that
other parents had given us that we’d tried

and… that’s what we did. There’s a whole
black market and grey market of drugs because

parents are so knowledgeable. I mean, there’s
Doctors, PHDs, MDs that have children with

neuroblastoma and it’s a very tight community
and they would do anything for anybody. In

fact, we, you know - that’s what we did
- created our own clinical trials for the

most part.

In randomised phase 3 trials, you have the
additional disincentive of placebo control

for half the patients. A quick glance at the
appalling enrolment rates around the world

and we can see that patient’s vote with
their feet.

It’s so obvious that if the FDA allowed
us to be rational about treating cancer patients,

we could move them all one hundred times faster.
As we did with AIDS, because what happened

was, the drug was good and the patients didn’t
have to die to prove it. And as you said in

the beginning ‘you need to do a randomised
phase 3 clinical trial’ No! if you have

phase two evidence that’s clear, if you
have an objective response, objective survival,

objective progression free survival, that’s
it… The truth is in itself. You don’t

have to do comparison, you have to have the
truth, you have to have reproducibility, you

have to have a lack of bias, and what you’ve
got there… that’s the answer man! The

AIDS guys did it. The cancer patients have
to do it. We have to force congress to change

legislation so that when a doctor and a patient
agree that the benefits succeed the potential

risk… that should go. Whatever way we make
it, that’s got to go.

New horizons

In all of the clinical trials to date, there
really hasn’t been much progress. Meanwhile,

those people however are dying. Yes, people
live a little bit longer with the standard

approach that we have now, but it’s not
much. And so, I would say this approach is

not working. It’s time to try something
else.

Traditionally, regulatory bodies have made
decisions that have been based on population

studies. So if you think about it for a moment…
We introduce a drug into a large population

in which we know there are many variables
in that population - people are different

– and we can’t control for those variables,
we don’t know what they are sometimes, we

just know they exist. So the way we dealt
with that in the past was to create this statistical

model of randomisation and, in fact, blinded
randomisation so we cover our eyes, and we

flip a coin, and we divide people up, and
we look for an outcome, and when we get an

outcome we put a statistical number on it,
and that gives us some assurance that yes,

that was really due to the drug and not something
else. Do we need that today? If I could go

into that population and I could - today - tell
you about those variables - which I couldn’t

before - because now I understand those genetic,
molecular make up of their individual cancer,

and I also under stand their genetic molecular
make up of them, as a person, and now I can

refine those populations. Do I still need
to put a blindfold on and flip a coin? Or

can I begin to be much more rational about
who I would treat with a particular drug and

who I would not. That is the adaptive trial
design. That is what cancer is teaching us

and telling us what we can now do, so we don’t
need to depend upon that old model. We can

be much more sophisticated, much more rational,
and we will get answers faster, we’ll be

much more certain that our answer is in fact
correct, and we will be able to allow patients

to have access to lifesaving drugs quicker,
faster, and with more assurance that they

are going to help them and not hurt them.

We accompanied Ben to University of California
Moore’s Cancer Centre to meet one of a new

generation of oncologists engaged in an ambitious
program of personalized medicine...

There’s two issues. One is, you know, what
are the best combinations for each particular

patient? Because, I think we all know that
glioblastoma is a different disease in every

single patient. If you took a hundred people
in a room there’s probably fifty diseases,

and so what we’re finding is that single
drugs seem to work better in some patients

than others because of the genetic make-up
of the tumour, and so when you talk about

combinations it’s even more complicated.
But we actually have a project where we’re

taking all the genetic information from each
patient, putting it into a computer, and coming

up with an answer to what drugs would be most
effective to each patient. So, it’s really

a personalised medicine approach to understanding
the genetics and using that information to

find the best combinations.

So as we move towards personalised medicine
where patients will receive combinations of

treatments, and that these combinations should
reflect the genetic characteristics of different

patients, then the only logical conclusion
to be drawn is that until we dismantle the

sanctity reserved for large-scale, randomised
phase III trials, we will never see meaningful

changes in patient survival.

Personalised medicine is the mantra. The irony
is that the practices up to now are directly

opposed to doing it. You can not – for most
of the randomised trials that are done, even

though you get a significant result – tell
an individual patient what the chances of

that treatment working for them will be. Right,
I mean, so, if you can’t do that, what you

started out… I mean the purpose of what
you started out to do - you’ve failed. You

need more homogeneous patients so that you
can actually say for this group of fairly

similar patients this particular treatment
will work. Well, you’re never going to do

randomised trials once you start thinking
in that framework of needing homogeneous patients.

Well if we don’t change the regulatory process,
what we’re already seeing is the biomedical

research enterprises collapsing. We’re seeing
investments beginning to dwindle because quite

frankly if you’re a venture capitalist or
an equity investor, you have far safer, quicker

opportunities for a return on investment than
to engage in hoping that a molecule - that

you’re going to be willing to fund very
early in it’s development – some how or

other is going to make its way through a 10-15
year process at the cost of over a billion

dollars to ultimately be able to give you
a return on that investment. So we’re seeing

negative consequences of not doing something,
and at the same time we also have the realisation

of the incredible opportunities if we would
do something and therefore, change has to

occur.

Acceleration

At the current rate of development of combination
therapy, testing combinations one by one,

it will take decades, and possibly centuries
to deliver more expansive cocktails to the

clinic. In the face of a clinical trial system
that is clearly failing, a new line of thought

is gaining traction in some oncology circles.
One man who is not hiding behind protocol,

is Marc Halatsch. He founded the International
Initiative for the Acceleration of Glioblastoma

Care as a framework to combine expertise and
engineer a treatment he feels will have a

better chance of combating cancer’s genetic
instability. This radical work involving untested

drug cocktails does not sit comfortably within
his scientific community, nor the pharmaceutical

companies Marc would normally enjoy sponsorship
from.

We have to (*) the protocol and that initially
involved 17 drugs. All of these drugs were

chosen to act in (*) against glioblastoma
to inhibit or suffocate signalling pathways

that are important for glioblastoma. We consciously
avoided to identify new targets for the glioblastoma

treatment. We were referring to drugs that
are approved are marketed for years for other

non-oncological indications and for which
a reasonable safety profile is already available.

So, the accelerated improvement means that
we are using drugs, that we want to use drugs

that are already available today, for which
we already have experience with human use

rather than identifying a new molecular target
and validating a candidate track for years

and years and then possibly finding out that
it doesn’t work. We have a rational basis

that these compounds are effective, that they
can be effective, and that they have reasonable

and justifiable risks even though we do not
know how these risks adapt when these substances

are combined.

During filming we were contacted by a senior
drug researcher for Glaxo-Smith-Klein in Cambridge

England, who had been diagnosed himself with
a high grade, inoperable brain tumour. He

refused to come on camera, even with his identity
hidden, but he was interested in Marc’s

paper, referring to the science behind it
as ‘beautiful’. But when he travelled

to a major centre for brain cancer in London,
in the hope of finding a forward thinking

clinician who might prescribe him the experimental
protocol, he was told the study was ‘unscientific’.

He died in 2014 leaving three young children.

Well if people say the paper is unscientific…
I think that it’s a judgement that cannot

be accepted because the paper is certainly
not unscientific. It is making a proposal

based on a set of hypothesis, and all of these
hypothesis are based on preclinical data,

on what we think is robust preclinical data.
What we can say for sure is that the recent

architecture of medical research for glioblastoma
patients has failed to bring out substantial

improvements for these patients and we don’t
know if you can do it better, but… we want

to try.

It is no coincidence that cancer cocktails
are first coming to light in the arena of

brain cancer. The limitations of surgical
intervention in the brain provide the impetus.

There’s a shift going on right now in a
lot of oncology where you may want to biopsy

a cancer, treat for four weeks with a mono
therapy (one drug), re-biopsy that cancer,

see if the genetics have changed, treat again
with a different drug for some period of time…

and so as the cancer shifts and mutates, you’re
changing your therapy accordingly.

If you don’t do that you may be treating
according to a profile that is simple outdated

because a tumour is a dynamic. The biological
situation may already have changed.

Now we can’t biopsy like that in the brain.
You can do that in the lung, the breast and

other answers… bone marrow. So we have to
figure out how’ll overcome those genetic

changes that will occur with treatment.

Well I believe, in the absence of bio-marker
profiles, it is very important to have a pragmatic

approach and to hit multiple targets at once
so that even if there is a change in the profile

and some pathways may compensate for other
inhibited pathways, you have a high chance

of maintaining a higher therapeutic pressure
against the tumour. In general, multi agent

protocol can be defended by pointing out the
heterogeneity of the tumour, and if you have

a set of drugs that act in concert then you
have a simple rule, and the rule is, the more

drugs you have the better you probably will
be able to address heterogeneity of the tumour.

This is an example of the new rational science
of treating cancer, based on the lessons that

cancer itself is teaching us. Yet what Marc
and his peers are pioneering, is in reality

revolutionary. The pharmaceutical companies
that own the drugs he is using have refused

financial support for his research, and he
is risking his professional reputation in

medical circles by even publishing this paper.
Cocktails are considered radical because if

such an ‘unscientific’ approach were to
work for patients, it would equate to opening

Pandora’s box, with the associated danger
of patients no longer being willing to accept

current medical practices. Few oncologists
would be willing to support such an investigation,

John Boockvar in New York, was an exception.

The idea of carpet bombing a cancer is an
appropriate idea where you just bombard the

tumour with multiple agents that will come
at it from different signalling pathways,

much like they do with HIV medicines, and
it will take that kind of approach to see

– I think – good outcomes. Of course our
delivery mechanisms, our ability to get these

drugs into tumours has to be better, our immune
systems in these patients has to be augmented,

improvement in immunotherapy will be an important
adjunct to any treatment, because if we cant

identify mutating cells or cells that are
distinct you have no chance… because chemotherapy

is only going to do so much without destroying
the natural body.

Never say die

Of all the patients we met during filming,
one man’s story stood out for his exceptional

courage and determination in the face of imminent
death. Anders Ferry is still fighting his

disease today, 15 years after being diagnosed
with terminal cancer at the age of 32. His

remarkable struggle for survival has encompassed
6 recurrences and 5 neurosurgeries including

some ground-breaking therapies and interventions.
Unable to travel alone, Anders and his father

Arne travelled to London at their own cost
from the far north of Sweden, to share his

story in this film.

Well I have been experimenting with my own
body and taking various odd combinations of

medications and non-mediations as well, under
very uncontrolled circumstances. So this has

been a marathon for me and for my wife in
particular. She has seen me through extremely

low points. The low points have been really
low, close to death.

Ander’s original course of chemotherapy
was stopped due to the development of a severe

rash, a result of sitting in a sauna trying
to raise his body temperature in order to

increase the efficacy of the chemotherapy,
Anders claims this rash released him from

a chemo educed mental-fog and afforded him
the clarity to do some preliminary research

online. He immediately enrolled on an innovative
American trial for an early immunological

compound. However, the compound was unapproved
in Europe at the time, so he had to smuggle

the drugs through customs as battery electrolytes.

So I was doing very well on that treatment,
but then after a couple of years they said

‘now we’re dropping the trial. Unfortunately
you won’t get anymore drug.’ And I panicked

of course. I thought, well this is what has
been keeping me alive for so long so I immediately

went into action to try to manufacture it
myself. As a physicist and physical chemist,

it wouldn’t be difficult for me to actually
create that molecule in the lab. So I pulled

all the patents and bought the chemicals,
borrowed lab resources, and my mother volunteered

to be my guinea pig to try it first before
I injected it myself.

At the eleventh hour, the founder of the drug
company, who had got wind of Anders’ desperate

attempt to stay on the medication, called
and insisted he did not use his own acetate,

instead sending him a life-time supply of
the drug the next day. By this time, it was

becoming clear to Anders that this was just
the beginning of his struggle, and that the

next challenge lay in combining different
treatments.

Well I got the idea to do several things simultaneously
when I read Ben Williams’ thoughts on it.

So I started adding little drugs that I could
access, gradually building up to a protocol

that involved many drugs in a big drug cocktail.
At its peak I was taking at least 8 prescription

drugs – off label… of course, they were
not chemotherapies, but assigned for entirely

different diagnosis – and lots of nutraceuticals.
The biggest obstacle to implement this protocol

has always been to actually find the prescription
drugs. They are available but you need somebody

to write the prescription, and I have been
lucky to have relatives and close friends

that could manage that for me. Sticking their
necks out. And occasionally my treating oncologist

has written out a few, but very reluctantly,
and has always been questioning ‘but why?

Is there any evidence for this?’ And I said
‘no, but there’s a potential in it.

Evidence is weak but there is some kind of hope.
Let’s try it, I’m willing.’ As the alternative

of doing nothing, you just look at the statistics…
every body dies within two years they said.

Well that’s not acceptable. By doing something
proactively, possibly ruining your health,

getting terrible side effects, but also possibly
getting real benefits, extending life. Like

I’m here now, a decade and a half later,
I’ve got two little kids, a happy wife,

a beautiful wife. My little Lynae and Tim
they are just my pride and joy of my life.

So, it has worked out well for me. Sure I
have deficits, but I can live with that. Life

with deficits is still life.

On three separate occasions, Anders has fought
back his cancer by combining conventional

surgery with innovative clinical trials, and
extensive, specifically tailored cocktails

of off-label drugs and nutraceuticals.

Well concerning the oncologists, I said ‘I’m
not really satisfied’ because when Anders

has his medication and it didn’t work and
the protocol didn’t work, they said ‘sorry

we can’t do anymore. You go home and play
with your girl’. I put the question, who

is responsible for their lives? Is it my son
who is supposed to take the care in his hand,

or is it so that the oncologist must have
some responsibility? He just can’t hide

behind the protocols.

Ander’s fight is one that is far from over,
and yet he too spends a great deal of his

time advising other patients, sharing whatever
knowledge or contacts he may have.

So ever since I created my internet persona
– Andrew Yassin – and hit the internet,

I’ve seen so many people come and go on
the lists. It’s terrible. Many people of

whom I’ve connected so strongly to, just
pass away. It’s dreadful.

Do you think that those patients were denied
something?

Absolutely, they were absolutely denied the
best care that could have been provided. I’m

sure many more would have been alive – or
at least had a much better chance to be alive

– if they had access to what I have been
doing for instance. I am also sure that this

approach could apply to other cancers, not
only brain tumours. I’ve seen effect in

advanced prostate cancers and breast cancers.
If I create a prescription of various off-label

drugs there is a viable option of prolonging
life for a long time, and that is also including

a creative and active life. I play my trumpet
at international jazz festivals. Perhaps not

at the same level as I could before having
all the surgeries, but still… it is a life

I enjoy and the kind I’m of proud of so
I’ve done well.

Reflections

Already facing a terminal diagnosis, should
cancer patients have to shoulder the additional

terror of unsupervised self-medication in
search of a meaningful attempt at survival?

None of the patients we spoke to wanted to
go it alone, they desperately wanted the reassurance

of professional medical supervision. Their
courage has showed us that the impossible

is sometimes possible, that there could be
a solution to problems we perceive as beyond

our reach.

I believe the medical community has an obligation
to do research into the cause – the clinical

cause of patients who have undertaken self-medications,
and who have reported extended life-span with

glioblastoma. I think it is an ethical obligation
of the medical community to try to understand

what happened with these patients, how they
did it, what their quality of life was and

how long they survived - these patients cannot
be ignored.

As survivors today, patients like Ben, Rich
and Anders stand as proof of principal. We

have the unprecedented opportunity to follow
this lead, employing the gifts that science

and technology are affording us to actively
embrace change. In the era of big data, Google,

and Apple, society can rationally ask the
medical establishment to reconsider its confidence

in a regulatory structure that served us well
in the past, but that appears slow, inefficient

and even inhumane in the context of terminal
disease today. The quid pro quo, that can

secure the continuation of a scientific methodology
and rational development of therapies, can

be the clinical data from EVERY patient. Retrospective
analysis of this data in the era of genomics,

can deliver the precious information we are
searching for in clinical trials, faster,

cheaper and more accurately.

Every professional I have ever talked to,
every oncologist, every neuro-oncologist,

every radio oncologist I’ve talked to, believes
that I am a freak chance, that my tumour would

have been put under control anyway, and that
my cocktail therapy didn’t contribute one

iota to it. They also think that Ben Williams
is a freak chance and that his 18 years would

have been given to him even without his experimentation,
and anybody that lives a long time – longer

than average - and uses a cocktail approach
is similarly dismissed as a freak chance.

But at a certain point, people are going to
have to start looking at the evidence.

Some will dismiss this evidence as merely
exceptions that prove the rule. But it is

hard to dismiss as coincidence Ben, Rich and
Anders’ shared academic background and scientific

training, unusual or illegal access to prescription
drugs, and the determination to overcome all

obstacles in the pursuit of their unorthodox
cancer therapies.

I’m quite sure that if I hadn't done what
I did I wouldn't be alive today. If I had

simply followed the prescription of my neuro-oncologist
I would have been just another statistic,

namely I would have lived another 12-18 months
and that would have been it. Because to my

knowledge he never had another long term survivor...

'Insanity is doing the same thing over and
over again, and expecting a different result'

– Albert Einstein

The Repurposing of Drugs in Oncology is an
initiative to provide oncologists with a robust,

independently researched database of old drugs
that could be helpful to combine with existing

standards of care across all cancers, enabling
them to prescribe off-label drugs with confidence

they will help and not hurt their patients.

With the support of a small charity in Belgium,
Marc Halatsch and Richard Kast’s CUSP9 cocktail

of drugs is in final stages of approval in
Germany for a phase 1 clinical trial for recurrent

glioblastoma. If the German regulatory authority
approve this trial in spring 2015 as anticipated,

they will set a global precedent for other
regulators to follow.

The film makers, together with the patients
and some of the doctors featured in this film,

are working with a UK charity to open an international
phase 1 clinical trial to investigate an expansive

cocktail approach for the newly diagnosed,
as an adjuvant therapy to the standard of

care for Glioblastoma. It remains to be seen
how such a proposal will be received by the

regulatory authorities across the world…

However, even if these trials go ahead, it
will take vast sums of money and many years

to ascertain if they hold benefit for patients.
Closing The Gap Now is an initiative to demonstrate

consensus within the scientific community
that patients with a prognosis of less than

24 months should be allowed access to any
treatment with phase 1 approval, in return

for donating their clinical data to an open-access
research database. The scientific community

would then be able to obtain certainty about
which treatments work for which patients much

faster, cheaper and more accurately than the
current system allows. www.closingthegapnow.org

For brain tumour patients who wish to view
extended interviews from this film please

visit www.virtualtrials.com