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Clinical Experience of Nadroparin in Patients with Cancer
Table 1: Nadroparin Studies in the Prevention of Venous Thromboembolism in Patients with Cancer
Study Setting Total Population Cancer Patients (%) Nadroparin Comparator
Pezzuoli et al.
26
General surgery 4,498 1,507 (33.5) 2,850 anti-Xa IU Placebo
(0.3ml) once daily
European Fraxiparin Study
27
Abdominal surgery 1,896 694 (36.6) 2,850 anti-Xa IU UFH 5,000U
(0.3ml) once daily 3 times daily
Simonneau et al.
28
Colorectal cancer surgery 1,288 1,288 (100) 2,850 anti-Xa IU Enoxaparin: 4,000 anti-Xa IU
(0.3ml) once daily (40mg) once daily
Bounameaux et al.
30
Abdominal surgery 194 92 (47.4) 2,850 anti-Xa IU Dalteparin: 2,500 anti-Xa IU
(0.3ml) once daily once daily
Marassi et al.
32
Abdominal surgery 61 61 (100) 2,850 anti-Xa IU No treatment
(0.3ml) once daily
Azorin et al.
36
Lung surgery 150 150 (100) 2,850 anti-Xa IU Nadroparin: 3,800
(0.3ml) once daily anti-Xa IU (0.4ml)
between 40 and 70kg;
5,700 anti-Xa IU (0.5ml)
between 71 and 110kg
Boncinelli et al.
37
Urological surgery 50 50 (100) 2,850 anti-Xa IU UFH 5,000U
(0.3ml) once daily 3 times daily
Nurmohamed et al.
39
Neurosurgery 485 400 (82.5 with brain or 2,850 anti-Xa IU (0.3ml) Graduated compression
spinal cord tumour) once daily + graduated stockings
compression stockings
Harenberg et al.
42
Bedridden medical patients 1,590 120 (7.5) 2,850 anti-Xa IU UFH 5,000U
(0.3ml) once daily three times daily
Weber et al.
43
Cancer patients under 20 20 (100) 2,850 anti-Xa IU No treatment
palliative care (0.3ml) once daily if <70kg
3,800 anti-Xa IU
(0.4ml) once daily if >70kg
Mismetti et al.
47
Cancer patients with central 59 59 (100) 2,850 anti-Xa IU Warfarin 1mg
venous catheters (0.3ml) once daily once daily
Niers et al.
48
Patients with a haematological 113 113 (100) 2,850 anti-Xa IU Placebo
cancer and a central venous (0.3ml) once daily
catheter
General Surgery given at a once-daily dose of 2,850 anti-Xa IU (0.3ml). Unfractionated
Nadroparin is the only low-molecular-weight heparin demonstrated to heparin was administered at a dose of 5,000U three times daily, the
reduce mortality in patients undergoing surgery. This was shown in a thromboprophylactic regimen of choice in this context. Both drugs were
randomised, double-blind trial comparing the efficacy and safety of initiated two hours pre-operatively, and treatment continued for seven days.
nadroparin versus placebo for preventing overall mortality and fatal Overall, nadroparin significantly (p<0.01) reduced the incidence of deep-vein
pulmonary embolism in 4,498 patients undergoing general surgery; thrombosis from 4.5% with unfractionated heparin to 2.8%. The incidence
approximately 65% of surgical procedures were abdominal surgery, and of deep-vein thrombosis was higher in cancer patients compared with non-
33% of patients were operated on for cancer.
26
Compared with placebo, cancer patients. Nevertheless, nadroparin also reduced the incidence of
nadroparin 2,850 anti-Xa IU or 0.3ml once daily significantly (p<0.05) deep-vein thrombosis in patients with cancer. No pulmonary embolism was
reduced overall mortality by 55.7% (95% confidence interval [CI] 10.7–78). observed in these patients. They had a higher bleeding tendency than non-
Nadroparin non-significantly reduced the incidence of pulmonary embolism cancer patients, but nadroparin was as safe in terms of bleeding risk as
by 50%, from 0.18 to 0.09%. During surgery, there was no significant unfractionated heparin, regardless of the presence of cancer.
difference in the number of patients requiring transfusions or in the number
of transfused units between the two study groups. Bleeding as assessed by A large randomised, double-blind study specifically performed in patients
the surgeon and the total amount of blood loss were significantly lower with colorectal cancer confirmed the value of nadroparin in this setting.
28
In
(p<0.05) in the placebo group. Similarly, post-operative bleeding was this trial, nadroparin 2,850 anti-Xa IU once daily or 0.3ml was compared
significantly less frequent (p<0.01) in the placebo group. However, no fatal with enoxaparin 4,000 anti-Xa IU or 40mg once daily, both drugs being
bleeding was reported, and bleeding complications did not result in a initiated two to four hours pre-operatively and administered for 9±2 days. In
significant difference in the number of study treatment discontinuations. No a total of 1,288 randomised patients, nadroparin was less effective for
subgroup analysis was performed in cancer patients. reducing asymptomatic distal deep-vein thrombosis, but more effective for
reducing symptomatic venous thromboembolism (see Table 2). Nadroparin
Abdominal Surgery was also safer in terms of major bleeding (p=0.012); this increased safety
Several studies have demonstrated the benefit of nadroparin in cancer was observed regardless of age or creatinine clearance.
29
patients undergoing abdominal surgery. A first randomised trial compared
the efficacy and safety of nadroparin with those of unfractionated heparin Other data obtained in a randomised, single-blind trial performed by
in 1,896 patients undergoing elective abdominal surgery, with a subset of Bounameaux et al.
30
support the high efficacy of nadroparin in abdominal
694 (36.6%) patients undergoing surgery for cancer.
27
Nadroparin was surgery patients. Nadroparin 2,850 anti-Xa IU once daily or 0.3ml was
EUROPEAN ONCOLOGY 35
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