Direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism.

Abstract

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism (PE), is a serious complication of cancer and its treatment. Patients with cancer have 4- to 7-fold higher risk of developing VTE than those without cancer [1]. Cancer patients with concurrent VTE have approximately 12% risk of bleeding during anticoagulation therapy and up to 25% annual risk of recurrent VTE [1]. The occurrence of VTE may also cause a delay or discontinuation of anti-cancer treatments, including chemotherapy and surgery [2]. Therefore, development of VTE in cancer patients has been associated with an increased risk of death [1]. In general, patients with VTE require anticoagulation therapy to prevent thrombus extension and death, which was largely associated with fatal PE, and to prevent recurrence in the long-term [2]. Traditionally, warfarin has been a common treatment strategy for patients with VTE; the use of warfarin in cancer patients, however, might be limited by complications of cancer and its treatment, including drug reactions, malnutrition, and the frequent need for dose adjustment [3]. As a result, low-molecular-weight-heparin (LMWH) was introduced as a suitable alternative anticoagulant because of few drug interactions and lack of requirement for routine laboratory monitoring; thus, it has been actively investigated in the treatment of cancer-associated VTE. A decade ago, the results of the phase III CLOT trial, which compared initial and maintenance therapy with dalteparin to warfarin therapy after initial dalteparin treatment in patients with cancer-associated VTE, were reported [4]. In this study, long-term dalteparin therapy was significantly associated with lower rates of 6-month cumulative incidence of recurrent VTE (9% vs. 17%) [4]. Since this study, LMWH has been the standard of care for initial and long-term therapy of patients with cancer-associated VTE. However, LMWH for long-term therapy requires a daily subcutaneous injection for cancer patients with VTE, which makes them feel uncomfortable. Thus, unmet needs are still present in the management of cancer-associated VTE.