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Crit Rev Oncol Hematol. 2018 Sep;129:102-112. doi: 10.1016/j.critrevonc.2018.06.015. Epub 2018 Jul 9.

Pharmacokinetic variability of anticoagulants in patients with cancer-associated thrombosis: Clinical consequences.

Author information

1
Centre d'Étude et de Recours aux Inhibiteurs de l'Angiogénèse, GH Cochin Port-Royal, HUPC, AP-HP, Paris Descartes, 75014 Paris, France; Service de cancérologie, Hôpital Cochin, AP-HP, Paris Descartes, CARPEM, 75014 Paris, France.
2
Centre d'Étude et de Recours aux Inhibiteurs de l'Angiogénèse, GH Cochin Port-Royal, HUPC, AP-HP, Paris Descartes, 75014 Paris, France; UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, AP-HP, Paris Descartes, CARPEM, 75014 Paris, France; UMR8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, France.
3
Centre d'Étude et de Recours aux Inhibiteurs de l'Angiogénèse, GH Cochin Port-Royal, HUPC, AP-HP, Paris Descartes, 75014 Paris, France; UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, AP-HP, Paris Descartes, CARPEM, 75014 Paris, France.
4
Inserm UMR-S1140, Paris, France; Université Paris Descartes, Sorbonne Paris Cite, Paris, France; Département d'hématologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
5
Centre d'Étude et de Recours aux Inhibiteurs de l'Angiogénèse, GH Cochin Port-Royal, HUPC, AP-HP, Paris Descartes, 75014 Paris, France; UF de Pharmacocinétique et Pharmacochimie, Hôpital Cochin, AP-HP, Paris Descartes, CARPEM, 75014 Paris, France; UMR8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, France. Electronic address: benoit.blanchet@aphp.fr.

Abstract

The use of anticoagulants in patients with cancer is challenging as several co-morbidities modifying pharmacokinetic (PK) parameters and significant drug-drug interactions with concomitant anti-neoplastic therapies may lead to PK variability resulting in increased risk of thrombosis or bleeding. Data on the management of patients with cancer-associated thrombosis (CAT) in real life are scarce since patients with cancer presenting with significant comorbidities tend to be excluded from large trials. This review is mostly based on case-reports and pharmacokinetics in an attempt to provide oncologists, with relevant orientation based on our best knowledge to date. Overall, low-molecular-weight heparins (LMWH) are the preferred option for the long-term prophylaxis and treatment of CAT as their benefit-risk was shown superior to vitamin K antagonists (VKA). Direct oral anticoagulants (DOAC) may represent an alternative to LMWH provided that a favorable benefit-risk in patients with CAT is evidenced in the future. We recommend a systematic risk-assessment including body composition, multiple medication, and renal function. Moreover a systematic and early discussion between pharmacist and oncologist should optimize the benefit-risk ratio for each patient.

KEYWORDS:

Anticoagulants; Cancer-associated thrombosis; Drug-drug interactions; Pharmacokinetics; Risk assessment

[Indexed for MEDLINE]

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