Download PDF
Phlebologie 2018; 47(06): 309-317
DOI: 10.12687/phleb2450-6-2018
Übersichtsarbeiten
Georg Thieme Verlag KG Stuttgart · New York

Novel clinical trial data on the treatment of cancer-associated venous thromboembolism with DOACs

Article in several languages: deutsch | English
M. Voigtlaender
1   II. Medizinische Klinik und Poliklinik, Hubertus Wald Tumorzentrum – Universitäres Cancer Center Hamburg (UCCH), Universitätsklinikum Hamburg-Eppendorf
,
J. Yamamura
2   Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie und Nuklearmedizin, Universitätsklinikum Hamburg-Eppendorf
,
F. Langer
1   II. Medizinische Klinik und Poliklinik, Hubertus Wald Tumorzentrum – Universitäres Cancer Center Hamburg (UCCH), Universitätsklinikum Hamburg-Eppendorf
› Author Affiliations
Further Information

Publication History

Eingegangen: 26 July 2018

Angenommen: 15 August 2018

Publication Date:
25 January 2019 (online)

Also available at
   Permissions and Reprints

Summary

Venous thromboembolism (VTE) is a frequent complication in patients with malignancy. Based on an improved safety and efficacy profile compared to vitamin K antagonists (VKA), current guidelines recommend anticoagulation with low-molecular-weight heparin (LMWH) for 3–6 months as the preferred treatment of cancer-associated VTE. Realworld evidence indicates, however, that guideline adherence is poor in clinical practice, a finding most likely explained by the daily subcutaneous injections and relatively high treatment costs associated with LMWH therapy. Although direct oral anticoagulants (DOACs) may be an attractive alternative owing to their ease of administration and favorable pharmacokinetics compared to VKA, the rather small and insufficiently characterized subgroups of cancer patients included in the large phase-3 trials did not allow translation of study findings into daily practice. With HOKUSAI VTE Cancer (edoxaban) and SELECT-D (rivaroxaban) two large prospective, randomized trials, which have compared DOACs with LMWH for the treatment of cancer-associated VTE, are now available. Both studies showed a reduction in recurrent VTE, but an increased risk in (gastrointestinal and urothelial) bleeding. Taking into account patient preferences and tumor characteristics, future treatment of cancer-associated VTE will thus require a high degree of selection and individualization.

Keywords

Direct oral anticoagulants - low-molecularweight heparin - cancer-associated venous thromboembolism - bleeding - gastrointestinal cancer
 

  • Literatur

  • 1 Levitan N, Dowlati A, Remick SC. et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancyRisk analysis using Medicare claims data. Medicine (Baltimore) 1999; 78 (05) 285-291.
    Search in Google Scholar
  • 2 Prandoni P, Lensing AW, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488.
    CrossrefPubMedSearch in Google Scholar
  • 3 Monreal M, Falgá C, Valdés M. et al. Riete Investigators. Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry. J Thromb Haemost 2006; Sep 04 (09) 1950-1956.
    CrossrefPubMedSearch in Google Scholar
  • 4 Bauersachs R. [Prolonged Secondary Prevention After Venous Thromboembolism]. Dtsch Med Wochenschr 2018; 143 (03) 137-142.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Lee AYY. Overview of VTE treatment in cancer according to clinical guidelines. Thromb Res 2018; 164 (Suppl. 01) S162-S167.
    CrossrefPubMedSearch in Google Scholar
  • 6 Carrier M, Cameron C, Delluc A, Castellucci L, Khorana AA, Lee AY. Efficacy and safety of anticoagulant therapy for the treatment of acute cancerassociated thrombosis: a systematic review and meta-analysis. Thromb Res 2014; 134 (06) 1214-1219.
    CrossrefPubMedSearch in Google Scholar
  • 7 Posch F, Konigsbrugge O, Zielinski C, Pabinger I, Ay C. Treatment of venous thromboembolism in patients with cancer: A network meta-analysis comparing efficacy and safety of anticoagulants. Thromb Res 2015; 136 (03) 582-589.
    CrossrefPubMedSearch in Google Scholar
  • 8 Kahale LA, Hakoum MB, Tsolakian IG. et al. Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer. Cochrane Database Syst Rev 2018; 06: CD006650.
    Search in Google Scholar
  • 9 Lee AY, Levine MN, Baker RI. et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 (02) 146-153.
    CrossrefPubMedSearch in Google Scholar
  • 10 Lee AY, Kamphuisen PW, Meyer G. et al. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA 2015; 314 (07) 677-686.
    CrossrefPubMedSearch in Google Scholar
  • 11 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149 (02) 315-352.
    CrossrefPubMedSearch in Google Scholar
  • 12 Farge D, Bounameaux H, Brenner B. et al. Inter national clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 2016; 17 (10) e452-e466.
    CrossrefPubMedSearch in Google Scholar
  • 13 Khorana AA, Yannicelli D, McCrae KR. et al. Evaluation of US prescription patterns: Are treatment guidelines for cancer-associated venous thromboembolism being followed?. Thromb Res 2016; 145: 51-53.
    CrossrefPubMedSearch in Google Scholar
  • 14 Khorana AA, McCrae KR, Milentijevic D. et al. Current practice patterns and patient persistence with anticoagulant treatments for cancer associated thrombosis. 20. Res Pract Thromb Haemost 2017; 01: 14-22.
    CrossrefPubMedSearch in Google Scholar
  • 15 Matzdorff A, Ledig B, Stuecker M, Riess H. Practice Patterns for Prophylaxis and Treatment of Venous Thromboembolism in German Cancer Patients. Oncol Res Treat 2016; 39 (04) 194-201.
    CrossrefPubMedSearch in Google Scholar
  • 16 Bona RD, Sivjee KY, Hickey AD, Wallace DM, Wajcs SB. The efficacy and safety of oral anticoagulation in patients with cancer. Thromb Haemost 1995; 74 (04) 1055-1058.
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Marshall AL, Campigotto F, Neuberg D, Rowe B, Connors JM. Recurrence of Venous Thromboembolism in Patients With Cancer Treated With Warfarin. Clin Appl Thromb Hemost 2015; 21 (07) 632-638.
    CrossrefPubMedSearch in Google Scholar
  • 18 Voigtlaender M, Langer F. Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism. What do we know so far? Hamostaseologie 2017; 37 (04) 241-255.
    PubMedSearch in Google Scholar
  • 19 Raskob GE, van Es N, Verhamme P. et al. Hokusai VTE Cancer Investigators. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med 2018; 378 (07) 615-624.
    CrossrefPubMedSearch in Google Scholar
  • 20 van Es N, Di Nisio M, Bleker SM. et al. Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. Thromb Haemost 2015; 114 (06) 1268-1276.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Young AM, Marshall A, Thirlwall J. et al. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol 2018; 36 (20) 2017-202322.
    CrossrefPubMedSearch in Google Scholar
  • 22 Li A, Garcia DA, Lyman GH, Carrier M. Direct oral anticoagulant (DOAC) versus low-molecularweight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res. 2018 (Epub ahead of print)
    PubMedSearch in Google Scholar
  • 23 Voigtlaender M, Langer F. A case-based practical approach to the management of cancer-associated venous thromboembolism. Vasa 2018; 47 (02) 77-89.
    CrossrefPubMedSearch in Google Scholar