Nimotuzumab goes on trial for head and neck cancer

Medical Tribune September 2008 SFVI
David Brill


A new phase II trial has been launched
in Singapore to investigate the use of
nimotuzumab as an adjunct to chemo-radiation
for treating squamous cell cancers of
the head and neck.
The study, a joint venture between the
National Cancer Centre Singapore and Innogene
Kalbiotech Pte. Ltd., is designed
to assess the drug’s effect on tumor size,
progression-free survival and toxicity. Up
to 37 patients with unresectable tumors
will receive the combined therapy for 8
weeks.
Nimotuzumab targets the epidermal
growth factor receptor (EGFR) to inhibit
the growth and spread of a tumor. The
efficacy of the drug is similar to others in
its class but it is less toxic and has a better
safety profile, according to Dr. Rikrik Ilyas,
director of Innogene.
“Patients are spared the discomfort of
severe skin rash and benefit from an enhanced
quality of life. As such, nimotuzumab
shows great potential to be used
as a long-term treatment that may allow
cancer to be managed as a chronic illness
rather than a lethal disease,” she said.
Nimotuzumab has already been approved
for use in various countries around
the world for head and neck cancers, but
in Southeast Asia this practice remains on a
named patient basis.
“At the moment we have patients from
Latin America, Canada, the US and Europe
… but none from ASEAN countries,” said
Ilyas.
“This [trial] will give us the opportunity
to enrich the database, extending it into
the Asian and ASEAN populations.”
Two patients have already been enrolled
in the trial, which is expected to be
completed within 2 years. A phase III trial
comprising around 700 patients is planned,
should phase II prove successful.

Helping patients reach the end of the road

Medical Tribune September 2008 SFVIII
David Brill


Delivering a terminal diagnosis and reviewing
a patient’s end-of-life options
can be demanding and often upsetting for
doctors, especially as most are not routinely
trained in these communication skills.
A new study shows, however, that
knowledge and confidence about end-of-life
discussions can be dramatically improved
by attending simple educational workshops
which involve practicing new skills in small
groups with support from instructors.
Doctors who took part also felt more at
ease talking to their colleagues about these
challenges, were more likely to plan for bad
news in advance and had improved intentions
of writing letters of condolence to bereaved
families in future.
The study’s senior author Professor Richard
Frankel said that many medical school
curricula, even in sub-specialties like medical
oncology, do not teach doctors how to
move from discussing cures to addressing
the issue of palliative care. As a result doctors
often have great difficulty with these
conversations and sometimes perceive the
patient’s condition as a failure on their part,
he said.
“This is an area where some cognitive
reframing is useful. Rather than thinking of
yourself as a failure because a patient’s life is
going to come to an end, thinking of this as
an opportunity to partner with patients right
up until the end produces some wonderful
results.
“A physician may go into it fearing that
they’ll get their own emotions involved and
stirred up, but I think that with some practice
and with some opportunities to practice
these difficult conversations can lead to extremely
meaningful patient partnerships
and really help patients to have the best end
of life that they can comfortably have,” said
Frankel.
The workshops were attended by 249
doctors, 103 of whom completed questionnaires
before and after. Statistically significant
changes were observed in measures of
knowledge, attitude change and professional
satisfaction.
The findings of the study were published
in The Journal of Psychosocial Oncology. [2008
26(3): 81-95]
Patients have a right to know their full
diagnosis and prognosis, and sharing this
knowledge appropriately can benefit all parties
involved, said Frankel, who is professor
of medicine and geriatrics at Indiana University
School of Medicine, US. He offered some
practical advice on how to approach these
subjects.
Doctors should prepare in advance by
asking their patients, at the stage of ordering
a diagnostic text, how they would like
any potentially upsetting findings to be
handled, he said. This avoids the situation
of having to speak into a “black box” with
no actual idea of what the patient’s preferences
are.
“Say something like: ‘everything is fine
right now, but if there were to be bad news at
some point, how would you like me to handle
it? Would you want to know everything,
would you want to know nothing, or would
you want to have a conversation to decide?’”
he said.
Frankel also advised using silence to allow
patients to process the news, rather than
simply marching on with more facts and figures.
“You’re potentially altering the entire
life of the patient in a very short period of
time and there’s only a limited amount that
people can retain when their entire lives are
transformed,” he said.

Screen high-risk patients for liver cancer, GPs urged

Medical Tribune September 2008 SFXIX
David Brill


A panel of experts has called on GPs to
step up screening for liver cancer, which
carries the second highest mortality of all the
common cancers.
As the prognosis of the disease continues
to improve, physicians need to take a more
active role in early case identification, the
group of specialists from the National Cancer
Centre Singapore (NCCS) said.
Speaking at the start of Liver Cancer
Awareness Month, they also advised GPs
to familiarize themselves with the latest advances
in diagnosis and treatment, encouraging
them to attend an educational forum
which will take place in September.
“As outcomes improve we need to become
more aware of what is potentially possible
for our patients in order to give them
hope as well as a chance of a cure,” said Professor
London Lucien Ooi, deputy director
of the NCCS and chairman of the campaign.
“GPs have a big role to play in prevention,
treatment and early screening, and they
need to understand that part.”
Hepatitis B carriers and people with cirrhosis
of the liver are at high risk for developing
cancer and should be screened every 6
months to a year, he said.
“For hepatitis B patients the risk of liver
cancer is about one hundred to three hundred
times more than in the normal population
… it’s a huge number and for that
it makes sense to screen them on a regular
basis,” he said.
The Ministry of Health is currently working
on a set of stand-alone guidelines for liver
cancer screening, according to Ooi, who
expects them to be published later this year.
In the meantime he recommended that
ultrasound and alpha fetoprotein be used for
screening, with the regularity decided on a
case-by-case basis. Once a potential tumor is
identified by ultrasound, MRI and CT can be
used for further investigation.
Left untreated, liver cancer kills most
patients within 6 months. Surgical resection
or transplantation, however, can extend life
to over 5 years in around half of patients,
Ooi said. Other promising new approaches
include transarterial chemoembolization,
radiofrequency ablation and percutaneous
ethanol injection, he added.
Liver Cancer Awareness Month is aimed
at both the public and medical community,
with a view to raising the profile of the disease
and promoting understanding of the
link to hepatitis B, which is the most common
cause of liver cancer and is highly prevalent
in East Asia.
Four hundred free hepatitis B screenings
are being offered at SingHealth Polyclinics,
and adults who have not been vaccinated are
being encouraged to do so.
Dr. Tan Yu Meng, deputy head of surgical
oncology at NCCS, said that in most cases
the tumor has already reached around 5 to 10
cm in diameter at the time of diagnosis.
“We want to get out the message that the
at-risk group needs to go and get themselves
screened because if you pick up these tumors
early then liver surgery, radiofrequency ablation
or chemotherapy can control your disease
very well,” he said.
The forum for GPs will be held on 20th
September, covering a range of subjects
from imaging through to treatment options.
There will also be an open case discussion,
with attendees encouraged to share their
own experiences.
A roundtable discussion for specialists
from both public and private institutions
will take place on 27th September.

Singapore to get access to cutting edge liver cancer treatments

Medical Tribune September 2008 SFXIII
David Brill


A recently announced agreement
is set to give Singapore
unprecedented access
to new drugs for liver cancer.
The 5-year deal will see AstraZeneca
open its research portfolio
on hepatocellular carcinoma
(HCC) to the National Cancer
Centre Singapore (NCCS) and National
University Hospital (NUH),
enabling them to take the most
promising new compounds into
preclinical and clinical trials.
A further part of the arrangement
will see a team of Singaporean
researchers travel to the
UK for training placements at the
Manchester Cancer Research Centre
(MCRC).
Under the agreement, one new
drug will be made available each
year for clinical testing in Singapore,
having already passed the
preclinical stages in the West. Six
previously untested compounds
will also be offered for preclinical
research each year, with the most
successful candidates progressing
to phase I and II clinical trials at
NCCS and NUH.
If these are successful then the
drugs will be moved on to phase
III trials, which could be extended
to other Asian countries through
the Asia-Pacific Hepatocellular
Carcinoma Trials Group, based at
NCCS. HCC is particularly common
in the continent, which is
thought to have three quarters of
the world’s patients.
“This opens up a new era of
drug development for HCC,” said
Dr. Goh Boon Cher, senior consultant
in the department of hematology-
oncology at NUH.
“Working together brings
Singapore to the fore and brings
compounds earlier to the clinic so
that they can benefit patients. Previously
we had to wait for quite
a period of time before these new
agents could be tested in a disease
which has such dismal outcomes,”
he said.
The first two compounds to
undergo clinical testing have been
named as AZD6244, a signal transduction
blocker, and AZD1152, a
selective inhibitor of cell division.
AstraZeneca will retain marketing
and development rights for all the
drugs made available through the
partnership.
“This devastating disease of liver
cancer kills a million people each
year worldwide, with a prognosis
such that 90 percent of patients will
not be here at the end of this alliance
in 5 years time,” said Dr. Andrew
Hughes, early development
senior director at AstraZeneca.
“We’ve taken a stance that this
is a disease which is crying out
for treatments,” he said, adding
that the information-sharing
model could be extended in future
to other conditions such as gastric
and nasopharyngeal cancer.
Ten placements will be available
at the MCRC, a project which
is also supported by the Singapore
Economic Development Board.
The training placements – five
for clinical researchers, two each
for nursing staff and clinical trial
managers and one for a statistician
– will last between 6 months and
2 years.
Registration for the placements
is expected to open shortly, with
the dates to be finalized once the
positions are filled. For footballmad
oncologists who need further
encouragement a trip to Old Trafford,
home of Manchester United,
is also on the itinerary.

Miniature insulin pump could hit shelves next year

Medical Tribune September 2008 P12
David Brill


Prototypes of a miniaturized insulin
pump, which are less than a quarter of
the size of existing devices, were unveiled
recently by a partnership of two Swiss
companies.
The NanopumpTM, which promises
greater convenience and comfort for diabetic
patients, has entered manufacturing
and could be ready for the market as soon
as next year.
The device can be fully programmed
by the patient, enabling them to input
their own specific insulin delivery schedule.
It is worn as a disposable skin patch,
connected to a storage reservoir, which
provides continuous subcutaneous infusion
throughout the day.
“The Nanopump represents the most
advanced use of microfluidic microelectro-
mechanical system technology in
diabetes treatment,” said Mr. Alberto de
Marco, director of the healthcare business
unit at STMicroelectronics, the Genevabased
company, which co-manufactured
the device.
“Semiconductor manufacturing technology
makes the Nanopump much more
affordable [when] compared to current
solutions, while reaching a higher magnitude
in terms of reliability and precision.
It is an attractive alternative to individual
insulin injections that must be administered
several times a day,” he said.
At present the NanopumpTM simply
follows its program and is unable to adjust
to the patient’s insulin levels. In future,
however, it could potentially be compatible
with continuous glucose monitoring
devices, de Marco said.
The prototype is the result of a partnership
between STMicroelectronics and
Debiotech, a medical device company
based in Lausanne, which was announced
in April last year.
Several failure-detection methods have
been incorporated into the NanopumpTM
in order to protect the patient from potential
malfunctions, de Marco added.

The David Beckham of science? Get real Dad

Medical Tribune August 2008 P16 - 17

Winning the Nobel Prize earned Sir Paul Nurse the respect of doctors, scientists
and reporters the world over. He told Medical Tribune’s David Brill what it
takes to become a Laureate, and why his daughter was less convinced.

There can be few achievements
in life that surpass
being knighted. But for a
Nobel-winning scientist there’s an
obvious trump card.
Sir Paul Nurse is one of the
privileged few who can say which
feels better. Driven by a passion
for wanting to learn how the natural
world worked, his career as
a biologist led to the “very pleasant
shock” of royal recognition in
1999.
But while his father was more
excited about the knighthood,
Nurse himself doesn’t hesitate
to name the 2001 Nobel Prize for
Physiology or Medicine as his
greatest success. Recognition of a
different kind was to follow, with
The Sun newspaper in his native
UK dubbing him “the David Beckham
of science” – an acknowledgment
of his failure to conform to
public stereotypes of white coats
and safety spectacles.
Seven years later the award
has finally sunk in, he says, but
the rapid elevation of status that
accompanies the Nobel Prize still
takes some getting used to.
“You’re really no different from
what you were before but it’s simply
that people take more notice
of you. Suddenly you become the
expert on almost anything, and not
just science. This can be slightly
embarrassing, because every time
you open your mouth you think
that someone’s going to write it
down.”
Nurse received the Nobel Prize
for his work on the molecular regulation
of the cell cycle – a research
interest which began in the 70s,
when his studies of yeast led him
to identify the cdc2 gene, which
plays an important role in controlling
the progression between the
stages of cell division. In 1987 he
discovered the human equivalent
– the CDK1 gene which encodes a
cyclin dependent kinase.
At the time of the award he
was director general of the Imperial
Cancer Research Fund (ICRF),
which later became part of the
charity Cancer Research UK. He
shared the Nobel Prize with Tim
Hunt, a British biochemist, and
Leland H. Hartwell, an American
scientist who is now director of the
Fred Hutchinson Cancer Research
Center in Seattle, US.
There are certain prerequisites
to winning the award, Nurse says,
noting that hopefuls need to be
“reasonably bright, but not necessarily
super-bright, and a reasonably
good scientist and experimentalist.”
Beyond the basics, however,
the first factor he identifies is circumstance.
“It does require a certain combination
of being in the right place
at the right time, which singles out
certain advances as being iconic,
and which can be clearly identified
with a few individuals. There are
many other advances – sequencing
the human genome is one which
everybody will talk about – but it’s
very difficult to identify the person
or limited group of people who are
involved in that.”
The second key to becoming
a Nobel laureate, he says, is to be
seen to be doing something that
other people aren’t. In his case a
long-standing interest in cell division
led him to begin his research
while the competition was limited,
and by the time others recognized
the importance of the field his reputation
within it was already established.
Author of over 200 scientific
papers – many of them in Nature,
Science and Cell – Nurse also emphasizes
the importance of being
able to write clearly and insightfully.
“Often people write papers
which can never be wrong because
they just agree with everything
that’s out there and then they’re
very muddy. You’ve got to stick
your neck out a bit at a stage where
you’re prepared to be wrong… if
you end up being right, then that’s
more clearly identifiable than if
you write something which says
‘it could be this or it could be that,’
because that lacks clarity.”
Nurse grew up in Wembley in
north-west London, going on to
study at the Universities of Birmingham
and East Anglia before
joining the ICRF in 1984. After a
5-year stint as chair of the department
of microbiology at The University
of Oxford, he returned to
the ICRF as scientific director in
1993 and was appointed director
general in 1996.
In 2003 he left the UK to become
president of Rockefeller
University in New York, a position
he still holds today. He is
also a regular visitor to Singapore,
where he chairs the scientific advisory
board of the Temasek Life
Sciences Laboratory.
Becoming a Nobel laureate is
like having another job in itself,
Nurse says, admitting that the many
extra requests on his time can be difficult
to manage. But describing his
profession as “a privilege,” it’s clear
that he wouldn’t want it any other
way. And should he ever get carried
away with his new-found fame, he
need only speak to his family to be
brought back down to earth.
“I’ve got two daughters – one’s
a scientist, the other’s a TV producer
and interviewer for soccer
who has interviewed David Beckham.
And when I pointed out The
Sun headline to her she just said
‘Get real Dad. You are not David
Beckham.’”

Unraveling complexities in cancer research

What has been the greatest
breakthrough in cancer
research in the past 10 years?
Identifying which genes become
altered in cancer, and in
which combinations, has been
a major advance. We now know
that there are 300 to 400 genes that
are important, and knowing those
does two things: firstly, it helps us
understand this immensely complicated
disease much better, and
secondly it gives us new targets
to think about for both diagnosis
and therapy.
What are the greatest
challenges facing the field in
the next 10 years?
The greatest challenge is dealing
with the wide range of changes
that can bring about the cancerous
state, and producing a rational
therapeutic response to all of
those different changes. Given that
complexity, it’s not going to be like
infectious disease research, for example,
where penicillin had a major
impact. Cancer’s going to be a
more brick-in-the-wall approach
– it’s going to gradually get better.
Cancer and breakthrough don’t go
together.
What advice would you give
to doctors who want to make
a career for themselves in
research?
There is one crucial factor: they
have to be driven by a passion for
wanting to know. Doing research
is very demanding and often not
rewarding. People think that it is,
but real success is very difficult to
achieve. You have to have a real
passion to cope with the fact that
the recognition and success that
come through are limited.
Who are your scientific
heroes?
Well I’m a biologist so I’m going
to be traditional and say Darwin
as my all-time hero. I can’t
help it. And he’s English, too. In
more recent years I think I’ve got
to say Francis Crick and maybe
Sydney Brenner, both of whom I
knew.
Several countries in the
Asia Pacific region are
becoming up-and-coming
centers for research. What
advice do you have for the
scientific community in these
countries at this stage?
The difficult trick to balance is
that you need to support science
across a fairly wide base. If you
only support research which is just
before application, which is the
tendency to do if you are looking
for commercial return, you really
are not investing in the future. And
if you only support basic research
which is looking for the future then
you don’t get the immediate commercial
return. What is required is
a broad-based approach that covers
the whole timeline.
What’s the best memory
from your childhood in
London?
I think my best memory really,
scientifically at least, was
being able to access all the great
museums in London. I happened
to be a bit of a museum kid so I
thought they were fantastic. I
think it inspired me, certainly in
part.

Managing diabetes in the primary care setting