Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications.
Reference (Study Name) | Patients ( | n | ) | Intervention | Duration (Months) | Major Bleeding (%) | b | Recurrent VTE (%) | b | Death (%) | b |
---|---|---|---|---|---|---|---|---|---|---|---|
LMWH compared with VKA | |||||||||||
Meyer et al. 2002 (CANTHANOX) [13] | Meyer et al. 2002 (CANTHANOX) [24] |
67 | Enoxaparin 1.5 mg/kg daily | 3 | 7 | 3 | 22.7 | ||||
71 | VKA | 16 | 4.2 | 11.3 | |||||||
Lee et al., 2003 (CLOT) [14] | Lee et al., 2003 (CLOT) [8] |
336 | Dalteparin 200 IU/kg daily for 1 month, and then 150 IU/kg | 6 | 4 | 9 | 39 | ||||
336 | VKA | 6 | 17 | 41 | |||||||
Deitcher et al. 2006 (ONCENOX) | a [15] | [25] | 29 | Enoxaparin 1 mg/kg daily | 3 | 6.5 | 6.9 | 6.5 | |||
32 | Enoxaparin 1.5 mg/kg daily | 11.1 | 6.3 | 19.4 | |||||||
30 | VKA | 2.9 | 10 | 8.8 | |||||||
Hull et al. 2006 (LITE) [16] | Hull et al. 2006 (LITE) [26] |
100 | Tinzaparin 175 IU/kg daily | 3 | 7 | 6 | 19 | ||||
100 | VKA | 7 | 10 | 20 | |||||||
Lee et al. 2015 (CATCH) [17] | Lee et al. 2015 (CATCH) [9] |
449 | Tinzaparin 175 IU/kg daily | 6 | 2.7 | 7.2 | 33 | ||||
451 | VKA | 2.4 | 10.5 | 31 | |||||||
DOAC compared with LMWH | |||||||||||
Raskob et al. 2018 (Hokusai-VTE Cancer) [18] | Raskob et al. 2018 (Hokusai-VTE Cancer) [16] |
522 | LMWH for ≥5 days, and then edoxaban 60 mg daily | 12 | 6.9 | 7.9 | 39.5 | ||||
524 | Dalteparin 200 IU/kg daily for 1 month, and then 150 IU/kg | 4.0 | 11.3 | 36.6 | |||||||
Young et al. 2018 (SELECT-D) [19] | Young et al. 2018 (SELECT-D) [17] |
203 | Rivaroxaban 15 mg twice daily for 3 weeks, and then 20 mg daily | 6 | 6 | 4 | 25 | ||||
203 | Dalteparin 200 IU/kg daily for 1 month, and then 150 IU/kg | 4 | 11 | 30 | |||||||
McBane et al. 2020 (ADAM-VTE) [20] | McBane et al. 2020 (ADAM-VTE) [27] |
145 | Apixaban 10 mg twice daily for 7 days, and then 5 mg twice daily | 6 | 0 | 0.7 | 16 | ||||
142 | Dalteparin 200 IU/kg daily for 1 month, and then 150 IU/kg | 1.4 | 6.3 | 11 | |||||||
Agnelli et al. 2020 (CARAVAGGIO) [21] | Agnelli et al. 2020 (CARAVAGGIO) [18] |
576 | Apixaban 10 mg twice daily for 7 days, and then 5 mg twice daily | 6 | 3.8 | 5.6 | 23.4 | ||||
579 | Dalteparin 200 IU/kg daily for 1 month, and then 150 IU/kg | 4.0 | 7.9 | 26.4 | |||||||
Planquette et al. 2021 (CASTA-DIVA) [22] | Planquette et al. 2021 (CASTA-DIVA) [28] |
74 | Rivaroxaban 15 mg twice daily for 3 weeks, and then 20 mg daily | 3 | 1.4 | 6.0 | 25.7 | ||||
84 | Dalteparin 200 IU/kg daily for 1 month, and then 150 IU/kg | 3.7 | 9.5 | 23.8 |
Anticoagulant | Creatinine Clearance (mL/min) | |||||||
---|---|---|---|---|---|---|---|---|
<15 or Dialysis | 15–29 | 30–50 | >50 | |||||
LMWH | ||||||||
Dalteparin [45] | Dalteparin [51] | Dose reduction should be considered | a | Dose reduction should be considered | a | 200 IU/kg once daily for 1 month, and then 150 IU/kg | 200 IU/kg once daily for 1 month, and then 150 IU/kg | |
Enoxaparin [46] | Enoxaparin [52] | 100 IU/kg once daily | 100 IU/kg once daily | 100 IU/kg twice daily | 100 IU/kg twice daily | |||
Tinzaparin [47] | Tinzaparin [53] | 175 IU/kg once daily | a | 175 IU/kg once daily | a | 175 IU/kg once daily | 175 IU/kg once daily | |
DOAC | ||||||||
Apixaban [43] | Apixaban [49] | Not recommended | 10 mg twice daily for 7 days, and then 5 mg twice daily | b | 10 mg twice daily for 7 days, and then 5 mg twice daily | b | 10 mg twice daily for 7 days, and then 5 mg twice daily | b |
Edoxaban [44] | Edoxaban [50] | Not recommended | Not recommended | 30 mg once daily (following initial 5–10 days of LMWH) | 60 mg once daily (following initial 5–10 days of LMWH) | |||
Rivaroxaban [42] | Rivaroxaban [48] | Not recommended | 15 mg twice daily for 3 weeks, and then 20 mg once daily | b | 15 mg twice daily for 3 weeks, and then 20 mg once daily | b | 15 mg twice daily for 3 weeks, and then 20 mg once daily | b |
Interacting Drug | Outcome | Proposed Mechanism of Interaction |
---|---|---|
Acalabrutinib | ↑ bleeding risk | Weak CYP3A4 inhibitor/antiplatelet effect |
Amiodarone | ↑ bleeding risk | Weak CYP3A4/P-gp inhibitor |
Carbamazepine | ↓ antithrombotic efficacy | Strong CYP3A4/P-gp inducer |
Clarithromycin | ↑ bleeding risk | Strong CYP3A4/P-gp inhibitor |
Cyclosporine | ↑ bleeding risk | Weak CYP3A4/P-gp inhibitor |
Diltiazem | ↑ bleeding risk | Moderate CYP3A4/P-gp inhibitor |
Efavirenz | ↓ antithrombotic efficacy | Moderate CYP3A4 inducer |
Fluconazole | ↑ bleeding risk | Moderate CYP3A4 inhibitor |
Ibrutinib | ↑ bleeding risk | Weak CYP3A4/P-gp inhibitor/antiplatelet effect |
Loperamide | ↑ bleeding risk | Mechanism unclear |
Miconazole (topical) | ↑ bleeding risk | Mechanism unclear |
Nevirapine | ↓ antithrombotic efficacy | Weak CYP3A4 inducer |
Oxcarbazepine | ↓ antithrombotic efficacy | Weak CYP3A4 inducer |
Phenobarbital | ↓ antithrombotic efficacy | Strong CYP3A4 inducer |
Phenytoin | ↓ antithrombotic efficacy | Strong CYP3A4/P-gp inducer |
Quinidine | ↑ bleeding risk | Moderate P-gp inhibitor |
Rifampicin | ↓ antithrombotic efficacy | Strong CYP3A4/P-gp inducer |
Ritonavir | ↑ bleeding risk | Strong CYP3A4/P-gp inhibitor |
Tocilizumab | ↓ antithrombotic efficacy | Indirect P-gp inducer |
Verapamil | ↑ bleeding risk | Moderate CYP3A4/P-gp inhibitor |