Statins recommended for certain 8-year-olds

Medical Tribune September 2008 P1 & 7
David Brill

Cholesterol-lowering statins should be
considered for certain children as young
as 8, the American Academy of Pediatrics
has advised.
The new guidelines, which prompted a
heated debate in parts of the international
media, have been hailed as timely by a specialist
in Singapore.
Low-fat milk is also recommended for
certain infants between 1 and 2 years old.
Rising childhood obesity rates and the
associated health risks give the recommendations
a “new urgency,” the authors wrote.
[Pediatrics 2008 Jul;122(1):198-208]
Doctors should still work aggressively
on lifestyle change, diet and weight status
before resorting to medications, said lead
author Dr. Stephen Daniels.
He said that although long-term studies
on the safety of statins in children are lacking,
the short-term data suggest a similar
profile to that seen in adults.
“While there may be things that we
don’t know yet … I think that as the data
accumulates the sense is that these agents,
when they are used appropriately, can be
effective in lowering cholesterol and are
generally safe,” said Daniels, who is pediatrician-
in-chief at The Children’s Hospital
in Denver, Colorado.
The guidelines received a mixed response
in the US, with people questioning whether
statins should be used in such young patients.
Daniels said however that only a small
minority of children would be medicated,
and most of these would be likely to have
familial hypercholesterolemia.

“I think many of them got a bit confused
about what we were really recommending
… there seemed to be this sense
among some reporters that we were recommending
statins for a large number of
children,” he said.
The guidelines state that medication
can be considered for children whose LDL
cholesterol level remains above 190 mg/
dl despite dietary therapy. For those with
other cardiovascular risk factors the recommended
cut-off point is 160 mg/dl.
Dr. Fabian Yap, head of pediatric endocrinology
at KK Women’s and Children’s
Hospital in Singapore, said that he has
already prescribed statins in patients as
young as 8, but emphasized the need for
a clear indication and close monitoring for
potential side effects.
He said that the guidelines will give
pediatricians greater flexibility in managing
obese children with lipid disorders.
“I think that the recommendation is
timely because it gives due recognition to
the fact that atherosclerosis has its roots in
childhood and that hypercholesterolemia,
which is a key modifiable risk factor for
future cardiovascular disease, ought to be
tackled as early as possible,” said Yap.
“There is unequivocal evidence that
statin therapy is the single most effective
method of lowering LDL cholesterol levels
in children and adolescents. However,
long-term safety data is obviously lacking,
which is the main reason why statin therapy
in young children ought to be undertaken
after careful risk-benefit analysis,
preferably by specialist pediatricians in a
tertiary referral center.”
Two separate meta-analyses have concluded
that statin therapy appears to be
safe for children aged 8 to 18 with familial
heterozygous hypercholesterolemia,
although only 2 years of follow-up data
is presently available. [Arterioscler Thromb
Vasc Biol 2007 Aug;27(8):1803-10; Atherosclerosis
2007 Dec;195(2):339-47]
The previous guidelines set 10 years
of age as the cut-off point for cholesterollowering
medications but limited the recommendations
to bile acid sequestrants.
[Pediatrics 1998 Jan;101:141-7]

Prescribe fenofibrate to prevent diabetic retinopathy, doctors urged

Medical Tribune September 2008 P4
David Brill


Doctors should routinely
consider prescribing fenofibrate
alongside statins for
their diabetic patients, two leading
experts advised recently.
A large multinational trial,
published last year in The Lancet,
showed that fenofibrate significantly
reduced the chances of
needing laser treatment for retinopathy
among type 2 diabetics.
[370(9600):1687-97]
Yet awareness of the condition
and the protective effects of fenofibrate
is low according to Anthony
Keech, professor of medicine, cardiology
and epidemiology and
deputy director of the National
Health and Medical Research
Council Clinical Trials Centre at the
University of Sydney, Australia. He
was speaking at a press conference
recently held in Singapore.
“Doctors need to know that diabetic
eye disease is highly prevalent.
And secondly they need to be
aware of these findings – that one
can actually retard the progression
of the condition easily with a oncea-
day tablet,” he said.
The Fenofibrate Intervention
and Event Lowering in Diabetes
(FIELD) study randomized 9,795
patients at 63 sites to placebo or
fenofibrate (200 mg/day).
After an average of 5 years follow-
up, 238 patients (4.9 percent)
in the placebo group had undergone
laser surgery compared to
just 164 (3.4 percent) of those in the
fenofibrate group – corresponding
to a hazard ratio of 0.69 (P=0.0002).
The safety profile of the drug was
similar to that of placebo.
“These are really sensational
findings that caused a great deal
of excitement around the world,
particularly as this is something
that statins don’t seem to do,” said
Keech, who was principal investigator
for the FIELD study.
“I think that as people become
aware of these results … they will
form the view that really there’s
no reason why you wouldn’t want
everybody with diabetes to be on
this treatment. Certainly if I had
diabetes I’d be running to get it,”
he said.
Laser treatment is proven to be
a successful treatment for retinopathy
but can reduce the visual field
and cause other ocular side-effects.
Professor Wong Tien Yin, one of
Singapore’s top ophthalmologists,
called on primary care physicians
to do more to prevent the development
of diabetic retinopathy.
“This is a message that needs
to go out to GPs, polyclinics, cardiologists
and diabetologists – those
people that manage diabetes.
“When [patients] see me for laser
treatment it’s quite late already.
We want them to start sorting it out
early, and we want to avoid laser
treatment … you can’t wait until
you have problems before you
go and see an ophthalmologist,”
he said, adding that awareness of
fenofibrate among doctors in Singapore
is currently “not there.”
In general around a third of
diabetics will develop retinopathy
at some point said Wong, who is
an ophthalmology professor at the
National University of Singapore
and deputy director of the Singapore
Eye Research Institute.
A study of 3,000 Singaporean
diabetics carried out last year found
that 35 percent were affected, yet
80 percent of them had not seen an
eye doctor and were unaware that
they had the condition, he said.
As the prevalence of diabetes
continues to rise throughout Asia,
fenofibrate will become an important
addition to other interventions
in tackling the disease, he added.
Keech added that unlike some
other fibrates, fenofibrate is safe in
combination with statins, and that
he sees no downside to the treatment.
“I think that within a few years
time people will believe that every
patient with diabetes should be on
fenofibrate, or a similar treatment,
for its macro- and microvascular
benefits,” he concluded.

Tau targeting offers new hope for Alzheimer's

Medical Tribune September 2008 P5
David Brill


A promising new treatment
has been shown to halt the
progression of cognitive
decline in patients with mild and
moderate forms of Alzheimer’s
disease.
The drug, a modified form of
methylthioninium chloride, targets
the tau protein tangles that develop
in the disease, whereas other drug
development efforts have largely
focused on the amyloid beta pathology.
A phase II randomized trial
found that the therapy reduced the
rate of cognitive decline by 81 percent
compared to placebo, following
50 weeks of treatment.
Cognitive function in drugtreated
patients did not change significantly
over 84 weeks compared
with baseline.
“So far we [have] the first clinical
trial to show that targeting tau
tangles may have some effect on
cognitive decline in Alzheimer’s
patients. So this is a complete
paradigm shift to current thinking
on the cause and the treatment of
Alzheimer’s in the world today,”
said Dr. Seng Shay Way, managing
director of TauRX Therapeutics,
the Singapore-based company
that developed the drug.
“This is very exciting and it
shows a lot of promise and potential.
But most importantly, if
we manage to tackle this disease
it will actually help a lot of families
and Alzheimer’s patients,” he
said.
Seng estimates that the drug,
which is taken orally three times a
day, could be commercially available
by 2012, depending on the results
of an upcoming international
phase III trial.
The present trial involved 321
subjects in Singapore and the UK.
Cognitive function was assessed
using the Alzheimer’s Disease
Assessment Scale Cognitive Subscale.
Brain imaging at 25 weeks
showed that the treatment was
having the greatest effect in areas
with the highest density of tau
tangles. This validates the theory
that tangles are an important
cause of dementia in Alzheimer’s,
Seng said.
Methylthioninium chloride
has been used in the past to treat
methemoglobinemia and urinary
tract infections. The modified
version contained in the drug appears
to dissolve the filaments of
tau tangles, thereby preventing
aggregation of the protein without
affecting its normal function.
The trial was a joint venture
between TauRX and researchers
from the University of Aberdeen
in Scotland. The results were presented
at the recent 2008 International
Conference on Alzheimer’s
Disease in Chicago, US, and at a
press conference in Singapore.
TauRX has yet to decide
whether to publish the phase II
results in a journal, Seng said, but
added that the phase III results
will be published when they are
available.

Oncogene obsession blinding oncologists, expert says

Medical Tribune September 2008 P6
David Brill

Cancer research has been wearing
blinders for the past 30 years, according
to a world-renowned expert who
spoke recently at the National Cancer Centre
in Singapore.
By being “obsessed with oncogenes,” the
international research community has largely
overlooked simpler targets for drug development,
said Professor Mak Tak Wah, who
believes that disrupting the metabolic pathways
of cancer cells could be the answer.
A growing volume of research shows that
cancer cells need large amounts of glucose
and fatty acids to grow and survive. Halting
this supply, Mak says, could be a way to
starve these cells and cause them to run out
of fuel.
“You could argue that targeted therapies
– 30 years of development, tens of billions of
dollars gone into anti-cancer agents – have
been a success, but I would say that on the
street, people are saying that we’ve failed.
You could argue that it’s really been a miserable
failure,” he told Medical Tribune.
“For the last 30 years, we’ve been betting
on the same horse. Is it not time for us
to think, well, what’s the payback? Some
people argue that it’s been a fantastic success
given the complexity of the problem. I argue
no, there are clearly simpler ways.”
Mak rose to scientific fame in 1984 when
his laboratory announced the first cloning
of the human T-cell receptor gene. He has
since played an important role in developing
genetically-modified mice for use in
immunological research, published over
600 research papers and won a multitude of
prestigious awards.
Current approaches to drug development
have led to some successes, Mak said, noting
that imatinib mesylate and trastuzumab can
actually save lives in some patients. Many
other drugs, however, are widely sold for
billions of dollars yet can only prolong life
by a few months.
Mak recently co-founded a company
called Agios Pharmaceuticals, which seeks
to develop drugs that regulate cancer metabolism.
He is joined in the venture by two
like-minded US professors: Craig Thompson,
who is scientific director of the Abramson
Family Cancer Research Institute at
the University of Pennsylvania, and Lewis
Cantley, chief of the division of signal transduction
at Harvard Medical School.
“We’re looking at the problem differently,”
said Mak, himself a professor at the
University of Toronto, Canada, and director
of the Campbell Family Institute for Breast
Cancer Research.
“We want to reignite this concept. You
can’t eat breakfast all day – we’ve been eating
breakfast for 30 years. Don’t you think
it’s time to change?”
The metabolism concept advocated by
the three professors has already begun to
yield results: Cantley’s group published two
papers in Nature earlier this year, identifying
the enzyme pyruvate kinase M2 as playing
an important role in the rapid growth of tumor
cells. [2008 Mar 13;452:181-6; 2008 Mar
13;452:230-3]
Others are finally beginning to take note
of these ideas, said Mak, who has been invited
to organize a session on cancer metabolism
for next year’s meeting of the American
Association for Cancer Research.
“Some people are saying ‘well let’s keep
an open mind and listen to these people.
They may be crazy but what the heck,’” he
said.
“It’s a different way. But every time you
start a wave you still need to start with a ripple.
Let’s see,” he concluded.

Regional academy offers hope for kidney dialysis patients

Medical Tribune September 2008 P6
David Brill


A new academy has opened in China
which could improve the quality of
life for kidney dialysis patients throughout
the Asia Pacific region.
The multi-million dollar center will
train nephrologists and nurses in peritoneal
dialysis (PD) – a home-based therapy
that avoids the inconvenience associated
with conventional hemodialysis.
Applicants are invited from across the
region, with a view to educating their colleagues
and setting up new centers when
they return home.
The academy, called Baxter Scientia
Asia Pacific, is a joint project between Baxter
International Inc. and the Peking University
Third Hospital in Beijing, where it
is based. It opened in July, with the first
training course due to start on 12 October.
“Around 40 percent of all the global
PD patients are in [the] Asia Pacific so this
is a very critical treatment for the lives of
many people in the region,” said Mr. Gerald
Lema, Baxter’s corporate vice president
and president of the Asia Pacific division.
“Our hope with this Scientia academy is
that … we will be able to disseminate many
good treatments and train physicians from
around Asia Pacific so that their standards
of care improve. People on dialysis have a
long-term commitment to therapy because
it’s a lifelong disease, so making a difference
in those outcomes really improves patients’
lives,” he said.
Lema expects that the center will take
on 100 trainees in its first year and 200 in its
second. The exact costs of the center have
not been disclosed, but it will be “a multimillion
dollar commitment over the next
few years,” he said.
The academy will also provide training
in other areas such as the management of
chronic kidney disease and its complications.
Research programs are also available
from later this year, and clinical trials are
planned for the future.
PD is convenient for patients as it can
be performed at home, whereas conventional
hemodialysis typically requires three
trips a week to a specialist center with each
session lasting around 4 hours.
Patients typically take around a week
to learn the techniques for PD, Lema said,
adding that the costs of treatment vary but
are generally comparable to hemodialysis
and can sometimes be cheaper.
Four different courses are presently on
offer at the academy, taught in English and
Mandarin. The longest is a 3-month program
offering basic training and experience
in PD.
Applicants can be nominated by
their home hospital or university. Scholarship
funding is available for certain
cases.

Flu jab less effective against pneumonia in the elderly

Medical Tribune September 2008 SFV
David Brill


The influenza vaccine appears to be
less effective than previously thought
at preventing pneumonia among the
elderly.
Research published recently in The Lancet
found that US senior citizens who were
vaccinated were no less likely to get community-
acquired pneumonia during flu
season than those who were not. [2008 Aug
2;372(9636):398-405]
The findings prompted a leading infectious
diseases expert in Singapore to call for
more studies into the efficacy of the vaccine
and the causes of pneumonia – a common
complication of influenza.
The study was conducted at the Group
Health Center for Health Studies in Seattle,
US. Lead author Dr. Michael Jackson said
that for the time being doctors should continue
to encourage their older patients to
get the flu jab.
“We know it’s effective in younger,
healthy seniors. We don’t know how effective
it is in the older seniors and seniors that have
chronic medical problems but it’s a very low
risk vaccine with an extremely low rate of side
effects so even a small amount of protection,
if it’s there, is beneficial,” said Jackson,
who is presently an epidemiologist at the US
Centers for Disease Control and Prevention.
The study could have two different interpretations,
the authors wrote. It is currently
unclear whether the vaccine is ineffective
at preventing influenza infection among
people who are at risk of pneumonia, or
whether influenza infection is only responsible
for a small proportion of pneumonias
in this group.
“The controversy calls for additional
studies to assess vaccine effectiveness, improve
understanding about causes of pneumonia
in elderly individuals and the impact
on health secondary to influenza illness not
restricted to pneumonia,” said associate professor
Leo Yee Sin, clinical director of the
Communicable Disease Centre in Singapore.
She noted, however, that conducting
randomized control trials could be difficult
given the ethical problems associated with
not vaccinating certain people.
Leo added that current recommendations
for vaccine strategy are “under intense
review,” as mortality studies have failed to
show that influenza-related deaths actually
decrease as vaccine coverage increases.
The paper by Jackson et al. was a nested
case-control study involving 1,173 confirmed
cases of pneumonia and 2,346 controls,
selected from a population of immunocompetent
seniors aged 65 to 94, who were
enrolled in a health maintenance organization
in Washington state, US.
Observational studies had previously
found that the influenza vaccine reduced
the odds of being admitted for pneumonia,
but were typically based on the International
Classification of Disease codes that are
assigned to a patient’s visit. These studies
did not adjust for important health differences
between vaccinated and unvaccinated
participants and were therefore subject
to confounding.
As a result these studies have tended to
overestimate the efficacy of the vaccine, Jackson
said. His research addressed these issues
by reviewing medical records to identify
more detailed patient information, which
could then be taken into account in risk adjustment
models.
When applying a fully adjusted model
– controlling for smoking history, previous
pneumonia episodes and use of corticosteroids
and bronchodilators, among other
factors – the odds ratio for developing pneumonia
during influenza season was 0.92
among those who had been vaccinated (95
percent CI 0.77 – 1.10; P=0.35).

GERD presentation not always by the book

Medical Tribune September 2008 SFV
David Brill


Doctors should be more wary of atypical
presentations of gastro-esophageal reflux
disease (GERD), a Singapore specialist
advised recently.
Although the classical symptoms are easily
recognizable, some 10 percent of patients
will not fulfill the usual criteria for GERD,
said Dr. Lui Hock Foong, chairman of the
National Foundation for Digestive Diseases.
These patients may present with coldlike
symptoms such as a sore throat, hoarse
voice or rhinitis. A chronic cough, particularly
occurring at night, can also be a sign
of GERD, and is thought to result from the
irritation of cough receptors at the lower
end of the esophagus.
Alternatively patients may have atypical
chest pain, prompting the physician to
carry out cardiac testing. If these results
come back negative, Lui said, it is possible
that the symptoms would respond to GERD
treatment.
Lui, a consultant gastroenterologist at
Gleneagles Hospital, said that knowledge
of these issues among GPs was beginning to
increase following an active campaign by the
Gastroenterological Society of Singapore to
educate about the symptoms of the disease.
He was speaking at the country’s first national
GERD awareness day on 20th August.
The condition was traditionally thought
to result from Western diets but appears to
be increasingly common in Asia. In Singapore
the prevalence rose from 1.6 to 9.9 percent
between 1994 and 1999. [J Gastroenterol
Hepatol 2005 Jul;20:995-1001]
Doctors who are faced with a possible
case of GERD should first take the time to
rule out other conditions, Lui said. Once the
diagnosis is confirmed the physician should
assess the severity of the problem using investigations
such as endoscopy, and should
check for long-term complications such as
alterations to the esophageal lining which
can predispose patients towards cancer.
A survey announced on the same day
found that public awareness of GERD is
low, with 76 percent of those who had experienced
symptoms admitting that they
had not heard of the condition. Only 42 percent
had sought treatment in the past, and
a quarter of these had waited more than a
year before doing so.
Two hundred and four people aged 25 to
60 with a history of GERD symptoms took
part in the survey. The awareness campaign
also included the distribution of a “call to
action” postcard, listing six simple steps to
help patients discuss their symptoms with
their doctor.

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