VTE in Solid Tumours: Dosing

Dosing

Active malignancy is associated with a 4–7 fold increase in venous thromboembolism (VTE) compared to patients without cancer1,2. Approximately 15% of patients with cancer develop future symptomatic VTE, and those with idiopathic VTE have up to a 4-fold increased risk of malignancy in the first year after VTE diagnosis.2 These cancers are likely to be advanced and are associated with a 3-fold increase in mortality2. For these patients, anticoagulation is an important consideration

Indication:

The extended treatment of symptomatic VTE and prevention of its recurrence in patients with solid tumours3

Recommended duration of treatment is 6 months; continuing treatment beyond this period should be evaluated according to individual risk/benefit ratio, taking into account the progression of cancer.

NICE clinical guidelines recommend offering low molecular weight heparins, such as Fragmin, to patients with active cancer and confirmed proximal deep vein thrombosis  (DVT) or pulmonary embolism (PE) for 6 months. At 6 months, the patient should be reevaluated4

Dosing regimen suitable for most solid tumour patients:

Once-daily, weight-adjusted monotherapy for 6 months3

Maximum daily dose – 18,000 IU**

No dose adjustment in the elderly

Dose adjustments are required in patients with low platelet counts.  For further information about dose reduction or interruption in patients with chemotherapy -induced thrombocytopenia, please refer to SPC.

Platelets should be measured before starting Fragmin and monitored closely in the first 3 weeks and regularly thereafter during treatment3
 

Monitoring of the anticoagulant effect is not usually necessary3

In the case of significant renal failure (defined as CrCl <30 ml/min), the dose of Fragmin should be adjusted based on anti-factor Xa activity

Please refer to the SmPC for monitoring within specific patient groups

Solid Tumours Dosing

**Maximum dose of 18,000 IU was used in patients weighing up to 132 kg in the Fragmin CLOT study3.
In cancer patients with body weight <40 kg at time of venous thromboembolic event, Fragmin should not be used for extended treatment of symptomatic VTE and prevention of its recurrences due to lack of data3.

Note:

Limited data are available regarding the safety and efficacy of antithrombotic therapy in patients with primary or metastatic tumours of the brain who develop concurrent thromboembolic events. There is a isk of fatal intracranial bleeding with use of anticoagulation in this category of patients. Therefore, if the treatment with Fragmin was considered, it should be monitored closely with regular re-assessment of the status of the tumour involvement of the brain and other individual risks.

For further information please refer to SPC.

References

1. Timp JF et al. Blood 2013;122:1712–1723.
2. Barsam SJ et al. Br J Haematol 2013;161:764–777.
3. Fragmin SmPC [extended treatment in Oncology (5,000-18,000 in syringe)]. Available at: https://www.medicines.org.uk/emc/search?q=fragmin
4. NICE clinical guideline 144. Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing. June 2012. Available at: https://www.nice.org.uk/guidance/cg144

*Including, but not limited to: congestive cardiac failure (NYHA class III or IV), acute respiratory failure or acute infection, who also have a predisposing risk factor for VTE such as age over 75 years, obesity, cancer or previous history of VTE.~
†In patients with chronic renal insufficiency or acute renal failure.

PP-FRA-GBR-0146.  June 2019