Home' Australian Pharmacist : Australian Pharmacist July 2012 Contents Australian Pharmacist July 2012 I ©Pharmaceutical Society of Australia Ltd. 547
OLD DRUG NEW INDICATION
Aspirin -- easing the
'headache' of cancer?
By Dr Lisa Nissen
Lisa Nissen is Associate Professor (QUM),
at the School of Pharmacy, University of
Queensland and Deputy-Director, Centre
for Safe and Effective Prescribing (CSEP).
Recorded by Hippocrates as relieving pain
as far back as 400BC, salicylates have been
used medicinally for thousands of years.
Although originally brewed from the
leaves of the willow tree (Cortex salicis)
the medicinal properties of salicylates,
including the relief of pain and fever, were
expanded when chemists successfully
synthesised salicylic acid in 1763. But
the extensive gut irritation caused by
this product limited its therapeutic
use until nally in 1897, Felix Ho man,
working in a Bayer laboratory, synthesised
acetylsalicylic acid -- or aspirin as we know
it today. Aspirin, a simple small white pill
became the world's rst synthetically
made drug and from its manufacture and
marketing our modern pharmaceutical
industry was born. Yet it is the potential
harnessed within that small pill to treat
all manner of conditions that makes the
revolution born from the simple willow
tree so extraordinary.
Aspirin's unique pharmacological
feature of irreversibly inhibiting
the cyclooxygenase (COX) enzyme,
primarily involved in the synthesis of
prostaglandins and thromboxane's,
gives aspirin perhaps one of its most
well-known therapeutic e ects --
that of anti-aggregation of platelets.
Platelet activity is substantially reduced
by a small dose of aspirin, with the
e ects of a single dose detectable for
up to 10 days. The bene ts of aspirin in
the relative reduction of cardiovascular
risk are well known and low dose aspirin
is widely used in the community for
this purpose. While the antithrombotic
bene ts of aspirin have been more
recently linked to potentially reducing
the cognitive decline in dementia and
Alzheimer's disease, it has been the
potential bene ts of aspirin in reducing
the risk of cancer that has sparked the
most interest in the medical community.
While the cardiovascular e ects of aspirin
are well known it has been suggested that
aspirin may also act by enhancing the
apoptosis of cells involved in early cancer,
therefore preventing the development
of cancer. Or it could be as simple as the
fact that aspirin reduces in ammation
and in ammation is associated with more
rapid turnover of cells and therefore
more chance of an error or mutation.
The results from a number of long term
trials, particularly in colorectal cancer
but also in other cancers (e.g. other
GIT, breast, ovarian, brain, lung and
pancreatic), have given us some clues on
how it should be used in the preventive
setting. What is clear from these studies
is that there is a long lag time before
the bene ts of the aspirin prevention
seems to kick in, with e ects being
seen generally after around ve years
of treatment and that bene t increases
with duration of treatment. Overall the
deaths from cancers in these studies were
reduced by around 20%.
Another point of interest in these studies
has been the dose of aspirin used.
Many of these trials use what would be
considered prophylactically as a 'high'
dose of aspirin, 600 mg per day. So there
are questions remaining around whether
low dose aspirin (e.g. 75--100 mg per day)
is as e ective in reducing cancer risk and
regardless of dose, how do you manage
the side-e ect risk of aspirin (e.g. GIT
complications) in both general and high
risk populations. We already consider
this scenario in clinical practice for our
cardiovascular patients. However, this
is often in a situation of secondary
prevention e.g. following a myocardial
infarction. Balancing the risk of a potential
cancer with gastrointestinal bleeding in
the primary prevention setting becomes
Aspirin may be a grandfather in the
eyes of our modern pharmaceutical
industry lled with biotechnology and
nanoparticles, but this simple chemical
seems to continue to nd new frontiers in
the industry it helped to begin.
• Cuzick J, Otto F, Baron JA, et al. Aspirin
and non-steroidal anti-in ammatory
drugs for cancer prevention: an
international consensus statement.
Lancet Oncol 2009;10:501--07.
• Burn J, Gerdes AM, Macrae F, et al.
Long-term e ect of aspirin on cancer
risk in carriers of hereditary colorectal
cancer: an analysis from the CAPP2
randomised controlled trial. Lancet.
• Rothwell PM, Fowkes FG, Belch JF, et
al. E ect of daily aspirin on long-term
risk of death due to cancer: analysis
of individual patient data from
randomised trials. Lancet.
'... this simple chemical
seems to continue to
find new frontiers in the
industry it helped to
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