Treating Venous Thromboembolism in Patients With Cancer

Caroline Piatek; Casey L O'Connell; Howard A Liebman

Disclosures

Expert Rev Hematol. 2012;5(2):201-209. 

In This Article

Risk Factors for Cancer-associated Thrombosis

Cancer is a well-established independent risk factor for VTE, associated with a 4.1-fold increase in VTE.[6] It is estimated that 15–20% of VTE events occur in cancer patients.[7] Factors that increase the risk of VTE among patients with cancer include type of cancer, advanced disease, surgery, chemotherapy and hospitalization.

Metastatic disease at the time of diagnosis is associated with a 1.4–21.5-fold higher risk of VTE compared with localized disease, depending on cancer type. Risk-adjusted models have shown that metastatic disease at the time of diagnosis is the strongest predictor of VTE within the first year of diagnosis.[8–13]

VTE is also a common complication of cancer-related surgery and is the most common cause of death at 30 days after surgery.[14] Cancer patients undergoing surgery have twice the risk of postoperative VTE compared with non-cancer patients undergoing the same surgery.[15] Higher rates of postoperative VTE are seen in patients undergoing abdominal surgery in comparison to urologic or gynecologic surgeries. Postoperative VTE is often a late complication of surgery, with 40% of events occurring more than 21 days after surgery.[14]

Hospitalization is one of the most significant risk factors for VTE, with a reported incidence between 2 and 7.8%.[1,2,16,17] In the hospitalized setting, the rate of VTE in cancer patients is twice that of non-cancer patients.[1] Predictors of VTE in hospitalized cancer patients include a more recent diagnosis of cancer, cancer site, stage and the type of cancer-directed treatment.[17,18] Among hospitalized cancer patients, those that develop VTE have a 2.1-fold increased risk of death during their hospitalization when compared with patients without VTE.[2]

Cancer patients on active therapy are also at increased risk of VTE. In a population-based study identifying risk factors for VTE in the general population, the use of chemotherapy was associated with a 6.5-fold greater risk of VTE compared with a 4.1-fold risk in cancer patients not on chemotherapy.[6] Among antineoplastic treatment, antiangiogenic agents including thalidomide, lenalidomide and bevacizumab have been associated with a particularly high risk of VTE.

Thalidomide and lenalidomide are immunomodulatory agents with antiangiogenic and anti-inflammatory properties that are commonly used in combination with dexamethasone or chemotherapy, such as doxorubicin, in the treatment of multiple myeloma. When thalidomide is used in combination with dexamethasone or chemotherapy, the VTE risk has been shown to be between 7 and 34%.[19–22] Lenalidomide in combination with dexamethasone or chemotherapy is associated with an 11% risk of VTE.[22–24] Based on this increased risk, the American Society of Clinical Oncology (ASCO) guidelines recommend the use of low-molecular-weight heparin (LMWH) or adjusted-dose warfarin (International Normalized Ratio [INR] 1.5) in multiple myeloma patients receiving thalidomide or lenalidomide plus dexamethasone and chemotherapy.[25] However, this recommendation is based on nonrandomized studies of multiple myeloma patients on thalidomide- or lenalidomide-based regimens, as well as extrapolation from studies of postoperative thromboprophylaxis in orthopedic surgery and a trial of adjusted-dose warfarin in breast cancer.[26–30] In a recent meta-analysis of multiple myeloma patients receiving thalidomide- or lenalidomide-based regimens, thromboprophylaxis seems to reduce the risk of VTE but no particular thromboprophylaxis strategy demonstrated a clear benefit.[19]

Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor thereby inhibiting angiogenesis. Bevacizumab, which is currently used in the treatment of a variety of solid tumors, has been associated with a 3–23% increased risk of VTE and 3% increased risk of arterial thrombotic events.[31–34] Gastric and colorectal cancers are associated with the highest risk of thrombosis among bevacizumab-treated patients.[35] However, in spite of a large body of evidence implicating bevacizumab in the increased VTE risk, a recent pooled analysis of patients in randomized Phase II and III studies failed to demonstrate a statistically significant increase in the unadjusted or exposure-adjusted incidence of all-grade VTE for bevacizumab-treated patient versus controls.[36]

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