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 Printable version |
Thromboembolic risk of thalidomide and antiangiogenic agents used to treat cancer |
Sang Thrombose Vaisseaux. Volume 20, Number 5, 227-38, mai 2008, Mini-revue
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 Résumé
Article gratuit
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Author(s) : Ludovic Drouet |
Summary : Although thalidomide is not the most potent nor the most specific antiangiogenic agent, venous thromboembolic events have been reported with the prescription of thalidomide in multiple myeloma. In keeping with this observation venous thromboembolic events have been reported in other indications of thalidomide and with thalidomide analogues (Lenalidomide and Actimid). The thrombotic side effects are mostly venous but arterial thrombotic events are also observed with the use of these molecules. An increase in thrombotic events are also observed with the other and more specific antiangiogenic agents. This was not recognised immediately since the situations in which they are prescribed (metastatic cancers) are already characterized by a high rate of thrombotic events. The prothrombotic effect of antiangiogenic agents is probably linked to an effect on the endothelium (decrease of antithrombotic activities and stimulation of a prothrombotic state). The other sides effects of antiangiogenic agents (hemorrhage, hypertension, proteinuria, microangiopathy, delay in scarring) are also probably related to endothelial effects. The prothrombotic effect of antiangiogenic agents appears to potentiate the prothrombotic conditions of the disease (myeloma, cancer) and the prothombotic effects of associated treatments (chemotherapy, high dose corticosteroids, erythropoietin). The increased thrombotic risk linked to prescription of antiangiogenic agents and specially of thalidomide and analogues for multiple myeloma is such that a preventive antithrombotic treatment is recommended. Some efficacy has been reported with the use of aspirin, oral anticoagulants and low molecular weight heparin. No head to head comparative trials have shown a superiority of any of these strategies. From published data, full dose oral anticoagulants appear to confer the highest hemorrhagic risk and perhaps low molecular weight heparin the best benefit to risk ratio. Thrombotic side effects appear less frequent with the more potent antiangiogenic drugs (direct inhibitors of VEGF or tyrosine kinase inhibitors antagonisation the signalling pathway of VEGF receptor) (than with thalidomide) even though venous, arterial and more specifically microvascular thrombotic events have been reported. In particular, when bevacizumab is administered intraocularly the risk of occlusion/thrombosis of retinal vessels does not appear to be significantly increased. |
Keywords : thalidomide, myeloma, thrombosis, cancer, antiangiogenic agents, VEGF |
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