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      Guidance for the prevention and treatment of cancer-associated venous thromboembolism

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          Abstract

          Venous thromboembolism (VTE) is a highly prevalent complication of malignancy with emerging changes in incidence, diagnosis and treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. We address a) the appropriate workup to search for occult malignancy in patients with idiopathic VTE, b) identification of high-risk cancer patients for primary thromboprophylaxis, c) the appropriate immediate and long-term treatment for people with cancer diagnosed with acute thromboembolism, d) the appropriate duration of anticoagulation and e) the appropriate treatment strategy in patients with recurrent VTE on anticoagulation. Areas of controversy and future directions in this field are highlighted.

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          Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

          Agnes Lee, Mark N Levine, Ross Baker … (2003)
          Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding. Copyright 2003 Massachusetts Medical Society
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            Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial.

            Agnes Lee, Pieter Kamphuisen, Guy Meyer … (2015)
            Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial.
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              Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials.

              Fabio Schutz, Joaquim Bellmunt, Y Je … (2010)
              Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib. PubMed databases were searched for articles published from January 1966 to July 2009, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings held between 2004 and 2009 were searched for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. A total of 10,255 patients were selected for this meta-analysis. The incidence for ATE was 1.4% (95% CI, 1.2% to 1.6%). The RR of ATEs associated with sorafenib and sunitinib was 3.03 (95% CI, 1.25 to 7.37; P = .015) compared with control patients. The analysis was also stratified for the underlying malignancy (renal cell cancer v non-renal cell cancer) and TKI (sunitinib v sorafenib), but no significant differences in incidence or RR were observed. Treatment with VEGFR TKIs sunitinib and sorafenib is associated with a significant increase in the risk of ATEs.
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                Author and article information

                Contributors
                Alok A. Khorana: khorana@ccf.org
                Journal
                Journal ID (nlm-ta): J Thromb Thrombolysis
                Journal ID (iso-abbrev): J. Thromb. Thrombolysis
                Title: Journal of Thrombosis and Thrombolysis
                Publisher: Springer US (New York )
                ISSN (Print): 0929-5305
                ISSN (Electronic): 1573-742X
                Publication date (Electronic): 16 January 2016
                Publication date PMC-release: 16 January 2016
                Publication date (Print): 2016
                Volume: 41
                Pages: 81-91
                Affiliations
                [ ]Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland Clinic, 9500 Euclid Ave, R35, Cleveland, OH 44195 USA
                [ ]Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON Canada
                [ ]Division of Hematology, University of Washington School of Medicine, Seattle, WA USA
                [ ]Department of Medicine, Thrombosis Program, University of British Columbia and Vancouver Coastal Health Authority, Vancouver, BC Canada
                Article
                Publisher ID: 1313
                DOI: 10.1007/s11239-015-1313-4
                PMC ID: 4715852
                PubMed ID: 26780740
                SO-VID: 0f6cb987-59a8-4f5f-8344-f8eb424985ea
                Copyright © © The Author(s) 2016
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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                Subject: Article
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                issue-copyright-statement © Springer Science+Business Media New York 2016

                ScienceOpen disciplines: Hematology
                Keywords: venous thromboembolism,prevention,risk factors,cancer,direct oral anticoagulants (doac),new oral anticoagulants (noac)
                Data availability:
                ScienceOpen disciplines: Hematology
                Keywords: venous thromboembolism, prevention, risk factors, cancer, direct oral anticoagulants (doac), new oral anticoagulants (noac)

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