Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study.

Internal and Vascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy.
The Lancet Oncology (Impact Factor: 24.73). 09/2009; 10(10):943-9. DOI: 10.1016/S1470-2045(09)70232-3
Source: PubMed

ABSTRACT Clinical trials are needed to assess the clinical benefit of antithrombotic prophylaxis in patients with cancer who are receiving chemotherapy, since these patients are at an increased risk of developing a thromboembolism. We did a trial to assess the clinical benefit of the low-molecular-weight heparin nadroparin for the prophylaxis of thromboembolic events in ambulatory patients receiving chemotherapy for metastatic or locally advanced solid cancer.
Between October, 2003, and May, 2007, ambulatory patients with lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer were randomly assigned in a double-blind manner to receive subcutaneous injections of nadroparin (3800 IU anti-Xa once a day, n=779) or placebo (n=387), in a 2:1 ratio. Study treatment was given for the duration of chemotherapy up to a maximum of 4 months. The primary study outcome was the composite of symptomatic venous or arterial thromboembolic events, as assessed by an independent adjudication committee. All randomised patients who received at least one dose of study treatment were included in the efficacy and safety analyses (modified intention-to-treat population). The study is registered with, NCT 00951574.
1150 patients were included in the primary efficacy and safety analyses: 769 patients in the nadroparin group and 381 patients in the placebo group. 15 (2.0%) of 769 patients treated with nadroparin and 15 (3.9%) of 381 patients treated with placebo had a thromboembolic event (single-sided p=0.02). Five (0.7%) of 769 patients in the nadroparin group and no patients in the placebo group had a major bleeding event (two-sided p=0.18). The incidences of minor bleeding were 7.4% (57 of 769) with nadroparin and 7.9% (30 of 381) with placebo. There were 121 (15.7%) serious adverse events in the nadroparin goup and 67 (17.6%) serious adverse events in the placebo group.
Nadroparin reduces the incidence of thromboembolic events in ambulatory patients with metastatic or locally advanced cancer who are receiving chemotherapy. Future studies should focus on patients who are at a high risk for thromboembolic events.
Italfarmaco SpA, Milan, Italy.

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    • "In recent studies also an association between CKD and risk of VTE was reported in the general population [12] [13]. In the cancer patient population, data on the association of CKD and VTE is scarce, because these patients are not comprehensively represented in most prospective observational studies and interventional trials [14] [15] [16]. The association of kidney disease and VTE was investigated in one retrospective cohort study based on ICD 10 coding [1]. "
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    ABSTRACT: Introduction The risk for occurrence of venous thromboembolism (VTE) in cancer patients has been the aim of numerous investigations. Chronic kidney disease (CKD) is a frequent comorbidity in cancer patients and has been found to be a risk factor for VTE in the general population. We investigated the association of CKD with VTE and mortality in cancer patients. Methods Patients were recruited into the prospective cohort study, Vienna Cancer and Thrombosis Study (CATS). CKD was estimated with equations for glomerular filtration rate (eGFR) based on serum creatinine by Modification of Diet in Renal Disease (MDRD), CKD Epidemiology collaboration (CKD-EPI) and Cockcroft-Gault equation (C-G). Patients were subsequently classified to stages of CKD according to the Kidney Diseases Outcomes Quality Initiative. Primary endpoint was occurrence of VTE and secondary endpoint was death. Results The cohort of 1100 patients was prospectively followed over a median of 723 days. CKD with an eGFR of under 90 ml/min was common with a prevalence of 71.1%, 67.0% or 51.5% of patients calculated with MDRD, CKD-EPI and C-G equations, respectively, but severe CKD (eGFR < 30 ml/min) was rare. Patients with a moderately decreased eGFR (90-60 ml/min/1.73 m2) based on CKD-EPI had a subdistribution hazard ratio of 0.68 (95% confidence interval 0.43-1.06). An association between CKD and occurrence of VTE or mortality could also not be shown with the other equations. Conclusions In our investigation of a large cohort of cancer patients with a high prevalence of CKD, a reduced eGFR was not an independent risk factor for occurrence of VTE or death.
    Thrombosis Research 07/2014; 134(1). DOI:10.1016/j.thromres.2014.04.002 · 2.43 Impact Factor
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    • "Several RCTs of thromboprophylaxis in ambulatory cancer patients have been reported including nine with LMWHs. The PROTECHT trial presented at the 2008 Meeting of the American Society of Hematology reported a significant reduction in the composite outcome of arterial and venous thrombosis [82]. The most dramatic impact on the absolute risk of VTE was observed in patients with advanced pancreatic cancer receiving specified chemotherapy [83] [84] [85]. "
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    ABSTRACT: The association between cancer and thrombosis has been recognized for more than 150 years. Not only are patients with cancer at a substantially increased risk of developing venous thromboembolism (VTE), the link between several coagulation factors and tumor growth, invasion, and the development of metastases has been established. Reported rates of VTE in patients with cancer have increased in recent years likely reflecting, in part, improved diagnosis with sophisticated imaging techniques as well as the impact of more aggressive cancer diagnosis, staging, and treatment. Various therapeutic interventions, such as surgery, chemotherapy, hormonal therapy, targeted therapeutic strategies as well as the frequent use of indwelling catheters and other invasive procedures also place cancer patients at increased risk of VTE. The increasing risk of VTE, the multitude of risk factors, and the greater risk of VTE recurrence and death among patients with cancer represent considerable challenges in modern clinical oncology. The American Society of Clinical Oncology (ASCO) originally developed guidelines for VTE in patients with cancer in 2007. ASCO recently updated clinical practice guidelines on the treatment and prevention of VTE in patients with cancer following an extensive systematic review of the literature. Revised 2013 guidelines have now been presented and will be discussed in this review. Although several new studies were identified and considered, many important questions remain regarding the relationship between thrombosis and cancer and the optimal care of patients at risk for VTE. © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 05/2014; 133 Suppl 2:S122-7. DOI:10.1016/S0049-3848(14)50021-7 · 2.43 Impact Factor
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    • "In the earliest randomized study, low dose of warfarin was reported to be safe and effective in reducing VTE complications in patients receiving chemotherapy for stage IV breast cancer, the relative risk reduction vs. placebo being 85% [23]. More recently, the PROTECHT study [24], showed a statistically significant 50% relative risk reduction in symptomatic thromboembolic events (2.0% vs. 3.9%) in favor of nadroparin in ambulatory cancer patients receiving chemotherapy for advanced cancer of breast, lung, gastrointestinal tract, pancreas, ovary and head and neck. The TOPIC-1 and TOPIC-2 studies, evaluated prophylaxis with certoparin once daily in patients with metastatic breast cancer (TOPIC-1) or advanced non small cell lung cancer (TOPIC-2) [25]. "
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    ABSTRACT: Venous thromboembolism (VTE) is frequently encountered in patients with cancer. Cancer patients have an increased risk of VTE during the entire course of their disease, but this risk is particularly high during the first months after cancer diagnosis and during the advanced stage of disease. VTE is a relevant cause of morbidity and mortality in patients with cancer and has a significant impact on their quality of life. Since 50 years, heparin and vitamin K antagonists are the mainstay anticoagulants for the prevention and treatment of VTE. At present, the treatment of VTE in patients with cancer does not differ from that of other medical patients. However, patients with cancer still have unmet clinical needs with the currently available antithrombotic agents. These patients are known to be at two- to four-fold risk for both VTE recurrence and anticoagulant-related bleeding, despite adequate anticoagulation, in comparison to non cancer patients Several new antithrombotic drugs targeting activated factor X or activated thrombin have been developed in the last decades for treatment of VTE. Some of them seems to have a potential therapeutic value for VTE treatment in patients with cancer, but no randomized studies have been specifically conducted in cancer patients. Until data with these novel agents in the specific oncology setting will be available, their efficacy and safety for both prevention and treatment of VTE in cancer patients remains to be defined.
    Thrombosis Research 04/2012; 129 Suppl 1:S101-5. DOI:10.1016/S0049-3848(12)70027-0 · 2.43 Impact Factor