Thrombotic Events in Patients With Cancer Receiving Antiangiogenesis Agents

University of Utah, Division of Hematology, Blood/Marrow Transplant and Myeloma Program, Salt Lake City, UT, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 09/2009; 27(29):4865-73. DOI: 10.1200/JCO.2009.22.3875
Source: PubMed


Tumor-associated neoangiogenesis has recently become a suitable target for antineoplastic drug development. In this overview, we discuss specific drug-associated hemostatic complications, the already known pathogenetic mechanisms involved, and the effect of varying antithrombotic strategies. Multiple agents with angiogenic inhibitory capacity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib, and sirolimus) have obtained US Food and Drug Administration approval, and many others have entered clinical trials. Arterial and venous thromboembolism and hemorrhage have emerged as significant toxicities associated with the use of angiogenesis inhibitors. We present a detailed analysis of the literature on thrombotic complication of antiangiogenic drugs. Close attention to hemostatic complications during antiangiogenic treatment is warranted. Further studies are required to better understand the pathophysiologic mechanisms involved and to define a safe prophylactic strategy.

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    • "The most thrombogenic chemotherapeutic agents are fluorouracil, cisplatin and paclitaxel (Khorana et al., 2005, 2013). A pro-thrombotic effect is recognized also for hormonal agents such as tamoxifene (Blom et al., 2005; Cuzick et al., 2007) and for antiangiogenetic agents, including monoclonal antibodies and tyrosine kinase inhibitors (Zangari et al., 2009; Raschi and De Ponti, 2012). "
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    • "The risk is additionally increased if chemotherapy is combined with steroids (Shen et al, 2011) or erythropoietin (Bennet et al, 2008). The inhibitors of angiogenesis (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib, and sirolimus) used as novel antineoplasic therapy are associated with an increase in arterial and venous thromboembolism and hemorrhage (Zangari et al, 2009). Gemcitabine is a deoxycytidine analogue related to cytarabine, that has been shown to improve evolution in patients with advanced PC. Deep venous thrombosis was found in one study in 3.2% of patients treated with gemcitabine (Kaye,1994). "

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