Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients With Cancer and Venous Thromboembolism

Lee, Agnes Y.Y.; Rickles, Frederick R.; Julian, Jim A.; Gent, Michael; Baker, Ross; Bowden, Chris; Kakkar, Ajay K.; Prins, Martin H.; Levine, Mark

doi:10.1200/jco.2005.03.133

Cited by 427 publications

(319 citation statements)

References 21 publications

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“…There is an intriguing association between cancer and VTE, with increased risks of VTE in patients with cancer, a high prevalence of occult cancer in patients presenting with idiopathic VTE, and some evidence that anti-coagulation can affect cancer biology and improve outcomes (Kakkar et al, 2004;Lee et al, 2005;Behanwala and Williamson, 2009). Although Virchow and Trousseau, respectively, provided insights into the pathophysiology of VTE and its association with cancer in the mid-nineteenth century, significant gaps exist in the understanding of cancer-associated VTE.…”

Section: Discussionmentioning

confidence: 99%

Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

et al. 2009

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BACKGROUND: The association between cancer, major surgery and venous thromboembolism (VTE) is well established. Multimodal therapy is increasingly being used as standard treatment for localised gastrointestinal cancer. The aim of this study was to examine the markers of pro-coagulation response and VTE risk in an exemplar multimodal model of pre-operative combination chemotherapy and radiation therapy, followed by complex cancer surgery. METHODS: Consecutive patients (n ¼ 36) with localised oesophageal cancer were studied at baseline after the first and second cycles of chemoradiation, and on post-operative days 1 -28, and at 3, 6 and 9 months. Factors regulating the pro-and anti-coagulant response, as well as pro-inflammatory markers including NFkB activation in peripheral blood mononuclear cells, were examined. All patients received enoxaparin 40 mg s.c. postoperatively up to discharge, and underwent pulmonary CT-pulmonary angiography and venography on day 10 postoperatively. RESULTS: Four (11%) non-fatal thromboembolic events were documented, all after hospital discharge. Neoadjuvant therapy before surgery activated factor VIII (FVIII) and pro-inflammatory NFkB, and increased D-dimers, pro-thrombin fragment 1 þ 2 (F1 þ 2) and the thrombin-anti-thrombin complex (TAT). Surgery significantly (Po0.05) increased pro-thrombin time (PT), activated partial thromboplastin time, fibrinogen, D-dimers, TAT, F1 þ 2 and FVIII up to 6 months. CONCLUSION: These data highlight the linked pro-coagulant and immunoinflammatory pathways in the multimodal management of oesophageal cancer, and suggest that the duration of current standard thromboprophylaxis regimens warrants further study.

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Section: Discussionmentioning

confidence: 99%

Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

et al. 2009

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“…Recently, large studies have demonstrated that subcutaneous low-molecular-weight heparin can be safely used and reduces the risk of TEE in patients with acute medical illnesses (Samama et al, 1999). Moreover, recent randomised trials have suggested that lowmolecular-weight heparin may be safer than vitamin K antagonists and that they may also be better in reducing the risk of TEE recurrence in cancer patients (Meyer et al, 2002;Lee et al, 2003Lee et al, , 2005. Thrombosis and germ-cell tumour K Fizazi et al…”

Section: Discussionmentioning

confidence: 99%

The risk of thrombo-embolic events is increased in patients with germ-cell tumours and can be predicted by serum lactate dehydrogenase and body surface area

et al. 2005

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The aim of this study was to evaluate the risk of thrombo-embolic events (TEE) in patients with germ-cell tumours (GCT) who receive cisplatin-based chemotherapy, to compare this risk to that of a matched control group of non-GCT cancer patients, and to identify risk factors of TEE. The rate of TEE during the 6 months following the initiation of chemotherapy was assessed in 100 consecutive patients with GCT and in 100 controls with various neoplasms who were matched on sex and age, and who received first-line cisplatin-based chemotherapy during the same period of time at Institut Gustave Roussy, Villejuif, France. Data were subsequently tested on a validation group of 77 GCT patients treated in Lyon, France. A total of 19 patients (19%) (95% confidence interval (CI): 13 -28) and six patients (6%) (95% CI: 3 -13) had a TEE in the GCT group and the non-GCT control group, respectively (relative risk (RR): 3.4; Po0.01). Three patients from the GCT group died of pulmonary embolism. In multivariate analysis, two factors had independent predictive value for TEE: a high body surface area (41.9 m 2 ) (RR: 5 (1.8 -13.9)) and an elevated serum lactate dehydrogenase (LDH) (RR: 6.4 (2.3 -18.2)). Patients with no risk factor (n ¼ 26) and those with at least one risk factor (n ¼ 71) had a probability of having a TEE of 4% (95% CI: 1 -19) and 26% (95% CI: 17 -37), respectively. In the GCT validation set, 10 (13%) patients had a TEE; patients with no risk factor and those with at least one risk factor had a probability of having a TEE of 0 and 17% (95% CI: 10 -29), respectively. Patients with GCT are at a higher risk for TEE than patients with non-GCT cancer while on cisplatin-based chemotherapy. This risk can be accurately predicted by serum LDH and body surface area. This predictive index may help to study prospectively the impact of thromboprophylaxis in GCT patients.

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“…Many retrospective analyses of clinical data indicated that heparin treatment affects survival of cancer patients with various tumors, especially in patients with the early stage of a disease [3][4][5]. Based on these observations several prospective clinical trials has been performed to evaluate heparins for its anticancer potential [6][7][8][9][10][11][12][13][14]. The CLOT study was designed to study the effect of LMWH or an oral anticoagulant -Coumarin on prevention of venous thromboembolism in patients with solid tumors [6,7].…”

Section: Heparin Affects On Cancer: Clinical Evidencementioning

confidence: 99%

“…Based on these observations several prospective clinical trials has been performed to evaluate heparins for its anticancer potential [6][7][8][9][10][11][12][13][14]. The CLOT study was designed to study the effect of LMWH or an oral anticoagulant -Coumarin on prevention of venous thromboembolism in patients with solid tumors [6,7]. While this study showed no overall effect on cancer progression, a significant increase in patient survival was detected in a subgroup of patients that were without metastasis at the beginning of the trial [6].…”

Section: Heparin Affects On Cancer: Clinical Evidencementioning

confidence: 99%

Heparin as an Inhibitor of Cancer Progression

Borsig

2010

Progress in Molecular Biology and Translational Science

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Heparin is frequently used for treatment of cancer-associated thromboembolism. Accumulating clinical evidence indicates that cancer patients treated with unfractionated and low-molecular weight heparin survives longer that patients treated by other anticoagulants, especially patients in the early stage of a disease. Experimental analysis from a number of animal models constantly provides evidence about the ability of heparin to attenuate metastasis. The non-anticoagulant activity of heparin on metastasis includes the ability to inhibit cell-cell-interaction through blocking of P-and L-selectin, to inhibit extracellular matrix protease-heparanase, and to inhibit angiogenesis. This chapter summarizes the current experimental evidence on the biology of heparin during cancer progression with the focus on potential mechanism of heparin antimetastatic activity.

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Randomized Comparison of Low Molecular Weight Heparin and Coumarin Derivatives on the Survival of Patients With Cancer and Venous Thromboembolism

Abstract: The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.

Cited by 427 publications

References 21 publications

Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

The risk of thrombo-embolic events is increased in patients with germ-cell tumours and can be predicted by serum lactate dehydrogenase and body surface area

Heparin as an Inhibitor of Cancer Progression

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