Meyer 7/4/09 11:33 am Page 20
Supportive Oncology
Low-molecular-weight Heparins in the
Management of Cancer-associated Thrombosis
a report by
Guy Meyer
Clinical Professor, Respiratory Medicine, Paris Descartes University, and
Attending Physician, Department of Respiratory and Intensive Care Medicine, European Hospital ‘George Pompidou’
Venous thromboembolism (VTE) is one of the most common complications 6.4%), kidney (1.2 versus 6%) and lung (1.1 versus 5%).
7
Further
in patients with cancer.
1
There is a strong association between the evidence of cancer-associated VTE was shown in a recent cohort study
incidence of VTE and cancer, with one-fifth of all new VTE events occurring of patients with lung cancer, who had a 4.4% annual incidence of
in patients with malignant disease.
2
VTE, with the risk being greatest during the first six months after
diagnosis and in patients with adenocarcinoma.
8
In addition, the risk
Patients with cancer have a seven-fold higher risk of VTE
3
and a reduced of VTE increased three-fold during chemotherapy, was doubled by
chance of surviving the event compared with non-cancer patients.
4
A radiotherapy and was six times higher for patients with distant
significant proportion of cancer patients with VTE have limited cancer metastases than for patients with localised lung tumours.
disease that in the absence of fatal pulmonary embolism (PE) would have
been associated with considerably longer survival.
5
The risk of thrombosis among acutely ill patients with cancer is being
increasingly recognised. In a large randomised comparison of
Incidence of Venous Thromboembolism in low-molecular-weight heparin (LMWH) and placebo in hospitalised
Patients with Cancer medical patients with acute illness, cancer was independently
The tumour itself is associated with the development of the associated with a 1.6-fold increase in the risk of VTE in the placebo
hypercoagulable state, but cancer patients are also exposed to a range of group.
9
In a study based on hospital discharge summaries of over a
iatrogenic factors known to independently increase the risk of VTE, million patients with cancer, hospitalised in one of 133 academic
including surgery, immobilisation, central venous catheters, chemo- medical centres in the US, symptomatic VTE was reported in 4.1% of
therapy, antioestrogen therapy or new antiangiogenic agents.
6
Several patients.
10
The rate of VTE increased by 28% from 1995 to 2003, due
sources of data are available for estimating the incidence and time to a near doubling of the PE rate. Subgroups of cancer patients with
course of symptomatic VTE among patients with different types and the highest rates of VTE included those with black ethnicity and
stages of cancer. patients receiving chemotherapy.
One large and recent study, based on the California cancer registry Data from the same group previously reported a 5.4% incidence of
linked to the California patient discharge data set, showed that of VTE in 66,106 adult neutropenic cancer patients hospitalised in 115
235,149 cancer cases, 1.6% were diagnosed with VTE within two medical centres.
11
Clinical variables associated with thromboembolism
years.
7
Metastatic disease at the time of diagnosis was the strongest included age over 65 years, primary site of cancer (including lung,
predictor of thromboembolism, with these patients having a 1.4–21.5- gastrointestinal, gynaecological and brain cancer), co-morbidities and
fold higher risk of VTE than patients with localised disease. The obesity. The in-hospital mortality rate was significantly greater among
incidence of VTE also varied according to the type of cancer. The patients with VTE than those without VTE (odds ratio [OR] 2.01; 95%
highest annual incidence of VTE was observed among patients with confidence interval [CI] 1.83–2.22), and this increase in mortality was
cancer of the pancreas (4.2% in localised disease versus 20% in observed in patients with localised cancer as well as those with
metastatic disease), stomach (2.5 versus 10.7%), uterus (0.8 versus advanced disease. In view of these risks, international guidelines
recommend the use of prophylaxis with low-dose unfractionated
heparin (UFH) or LMWH for patients with active cancer who are
Guy Meyer is a Clinical Professor of Respiratory Medicine at
confined to bed in hospital.
12,13
Paris Descartes University and an Attending Physician in the
Department of Respiratory and Intensive Care Medicine at
the European Hospital ‘George Pompidou’ in Paris. He is Treatment of Venous Thromboembolism in
running a large, multicentre, randomised, controlled trial to
Patients with Cancer
evaluate the effect of adjuvant treatment with low-
molecular-weight heparins on the survival of patients with
localised lung cancer. He is involved in clinical research on
Initial Treatment
the diagnosis, epidemiology and treatment of pulmonary
Heparins are commonly used for the initial treatment of VTE in cancer
embolism, and has been working on the relationship of thromboembolism and cancer. He
was involved in the CANTHANOX study evaluating the effect of enoxaparin in the outcome patients. Compared with UFH, LMWH is easier to administer and does
of patients with venous thromboembolism and cancer. Dr Meyer received his MD from
not require dose adjustment or monitoring.
14
A meta-analysis of studies
Lariboisiere-Saint-Louis Faculty of Medicine, Paris VII University in 1986 and trained in
respiratory medicine and intensive care at Laennec Hospital in Paris.
comparing UFH with LMWH for the initial treatment of VTE suggests that
in cancer patients initial treatment with LMWH is at least as safe and
E: guy.meyer@hop.egp.aphp.fr
effective as UFH. The same data suggest that LMWH may be associated
with a reduced mortality risk in these patients.
15
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