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

Neue Studiendaten zur Therapie der tumorassoziierten venösen Thromboembolie mit DOAKs

Artikel in mehreren Sprachen: 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
› Institutsangaben
Weitere Informationen

Korrespondenzadresse

Prof. Dr. med. Florian Langer
II. Medizinische Klinik und Poliklinik
Hubertus Wald Tumorzentrum – Universitäres Cancer
Center Hamburg (UCCH)
Universitätsklinikum Eppendorf
Martinistr. 52, D-20246 Hamburg
Telefon: +49 40/7410–52453/-50664   
Fax: +49 40/7410–55193   

Publikationsverlauf

Eingegangen: 26. Juli 2018

Angenommen: 15. August 2018

Publikationsdatum:
25. Januar 2019 (online)

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Zusammenfassung

Die venöse Thromboembolie (VTE) ist eine häufige Komplikation bei Patienten mit maligner Grunderkrankung. Basierend auf einer verbesserten Wirksamkeit und Sicherheit gegenüber Vitamin K-Antagonisten (VKA) empfehlen aktuelle Leitlinien eine 3- bis 6-monatige Antikoagulation mit niedermolekularem Heparin (NMH) als Standardtherapie der tumorassoziierten VTE. Versorgungsdaten zeigen jedoch eine geringe Leitlinienadhärenz im klinischen Behandlungsalltag, was am ehesten auf die täglichen subkutanen Injektionen und die relativ hohen Therapiekosten zurückzuführen ist. Aufgrund ihres Einnahmemodus und ihrer im Vergleich zu VKA günstigen Pharmakokinetik stellen die direkten oralen Antikoagulantien (DOAKs) zwar eine vielversprechende Alternative dar; die Subgruppen der in die großen Zulassungsstudien eingeschlossenen Krebspatienten waren aber aufgrund ihrer Größe und Tumorcharakteristika nicht geeignet, die bisherigen Studiendaten in den klinischen Alltag zu übertragen. Mit HOKUSAI VTE Cancer (Edoxaban) und SELECT-D (Rivaroxaban) stehen nun die Ergebnisse von zwei prospektiven, randomisierten Studien zur Verfügung, die die Wirksamkeit und Sicherheit von DOAKs im Vergleich zu NMH bei Patienten mit tumorassoziierter VTE untersucht haben. In beiden Studien war die DOAK-Einnahme mit weniger VTE-Rezidiven, jedoch mit einer höheren Rate an (gastrointestinalen und urothelialen) Blutungen assoziiert. Somit wird die zukünftige Therapie der tumorassoziierten VTE unter Berücksichtigung von Patientenpräferenz und Tumorcharakteristika ein hohes Maß an Selektion und Individualisierung erfordern.


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Schlüsselwörter

Direkte orale Antikoagulantien - niedermolekulares Heparin - tumorassoziierte venöse Thromboembolie - Blutungen - gastrointestinaler Tumor

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  • 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.
    Suche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche in Google Scholar
  • 4 Bauersachs R. [Prolonged Secondary Prevention After Venous Thromboembolism]. Dtsch Med Wochenschr 2018; 143 (03) 137-142.
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Lee AYY. Overview of VTE treatment in cancer according to clinical guidelines. Thromb Res 2018; 164 (Suppl. 01) S162-S167.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    Suche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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 ConnectPubMedSuche 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.
    CrossrefPubMedSuche 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.
    PubMedSuche 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.
    CrossrefPubMedSuche 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 ConnectPubMedSuche 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.
    CrossrefPubMedSuche 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)
    PubMedSuche 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.
    CrossrefPubMedSuche in Google Scholar

Korrespondenzadresse

Prof. Dr. med. Florian Langer
II. Medizinische Klinik und Poliklinik
Hubertus Wald Tumorzentrum – Universitäres Cancer
Center Hamburg (UCCH)
Universitätsklinikum Eppendorf
Martinistr. 52, D-20246 Hamburg
Telefon: +49 40/7410–52453/-50664   
Fax: +49 40/7410–55193   

  • 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.
    Suche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche in Google Scholar
  • 4 Bauersachs R. [Prolonged Secondary Prevention After Venous Thromboembolism]. Dtsch Med Wochenschr 2018; 143 (03) 137-142.
    Thieme ConnectPubMedSuche in Google Scholar
  • 5 Lee AYY. Overview of VTE treatment in cancer according to clinical guidelines. Thromb Res 2018; 164 (Suppl. 01) S162-S167.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    Suche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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.
    CrossrefPubMedSuche 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 ConnectPubMedSuche 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.
    CrossrefPubMedSuche 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.
    PubMedSuche 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.
    CrossrefPubMedSuche 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 ConnectPubMedSuche 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.
    CrossrefPubMedSuche 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)
    PubMedSuche 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.
    CrossrefPubMedSuche in Google Scholar

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