Originally published as JCO Early Release 10.1200/JCO.2009.22.4584 on September 8 2009

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Impact of Venous Thromboembolism and Anticoagulation on Cancer and Cancer Survival

From the Division of Hematology/Oncology and the Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC; and the James P. Wilmot Cancer Center and the Department of Medicine, University of Rochester, Rochester, NY.

Corresponding author: Nicole M. Kuderer, MD, Division of Hematology, Oncology and Cellular Therapy, Duke Comprehensive Cancer Center, Duke University Medical Center, DUMC 3841, Durham, NC 27710; e-mail: nicole.kuderer{at}duke.edu.

Changes in the hemostatic system and chronic hemostatic activation are frequently observed in patients with cancer, even in the absence of venous thromboembolism (VTE). VTE is a leading cause of death among patients with cancer and contributes to long-term mortality in patients with early as well as advanced-stage cancer. Mounting evidence suggests that components of the clotting cascade and associated vascular factors play an integral part in tumor progression, invasion, angiogenesis, and metastasis formation. Furthermore, there are intriguing in vitro and animal findings that anticoagulants, in particular the low molecular weight heparins (LMWHs), exert an antineoplastic effect through multiple mechanisms, including interference with tumor cell adhesion, invasion, metastasis formation, angiogenesis, and the immune system. Several relatively small randomized controlled clinical trials of anticoagulation as cancer therapy in patients without a VTE diagnosis have been completed. These comprise studies with LMWH, unfractionated heparin, and vitamin K antagonists, with overall encouraging but nonconclusive results and some limitations. Meta-analyses performed for the American Society of Clinical Oncology VTE Guidelines Committee and the Cochrane Collaboration suggest overall favorable effects of anticoagulation on survival of patients with cancer, mainly with LMWH. However, definitive clinical trials have been elusive and questions remain regarding the importance of tumor type and stage on treatment efficacy, the impact of fatal thromboembolic events, optimal anticoagulation therapy, and safety with differing chemotherapy regimens. Although the LMWHs and related agents hold promise for improving outcomes in patients with cancer, additional studies of their efficacy and safety in this setting are needed.

Supported by Grants No. NIH 5T32 CA009307-30 from the National Cancer Institute (N.M.K.), 1R01HL095109-01 from the National Heart, Lung and Blood Institute (C.W.F.), U01 HL072289 and U54 HL77878; and U01 DD000014 from the Centers for Disease Control and Prevention (T.L.O.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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