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

Expert Commentary & Five-year View

There are still a number of important unanswered questions in the long-term management of cancer-related VTE. Whether the Khorana or CATS risk model can be utilized to select cancer patients at high risk for pharmacologic prophylaxis is not known. A clinical trial to assess the efficacy and safety of the Khorana approach is underway.[101] Several studies have shown that primary prophylaxis in ambulatory cancer patients may reduce the rate of VTE without a significant increase in bleeding complications.[80–82]

Although LMWHs have proved to be more effective than oral VKA in the prevention of recurrent VTE among cancer patients, their use beyond 6 months has not been studied. Several studies are currently underway investigating the duration of various preparations of LMWH for long-term prevention of recurrent VTE in patients with cancer as well as their efficacy compared with VKA.[102–104] Emerging research suggests that LMWHs may have a variety of antineoplastic effects, and their use may increase survival in cancer patients.[83,84]

Unfortunately, patients bear the burden of daily injections, storage and disposal issues, and costs related to the long-term use of LMWH. The new oral anticoagulants may provide a long-awaited alternative for such patients, as well as those presenting with a newly diagnosed VTE, with the added benefit of reliable dosing and few drug interactions. Among the new drugs being investigated are LMWHs, such as bemiparin and semuloparin, and oral factor Xa inhibitors, such as rivaroxaban and apixaban.

Bemiparin is a parenteral LMWH with anti-factor Xa and anti-factor IIa activity. In the CANBESURE trial, prolonged prophylaxis (28 days) with bemiparin was compared with shorter duration prophylaxis (8 days) with bemiparin in patients undergoing abdominal or pelvic cancer surgery. Prolonged prophylaxis with bemiparin resulted in an 82.4% risk reduction of VTE without significant increase in bleeding (p = 0.010).[85]

Semuloparin is a parenteral ultra-LMWH with anti-factor Xa activity and residual anti-factor IIa activity. In a recent Phase III study of 3212 patients initiating a chemotherapy regimen for locally advanced or metastatic solid tumor, there was a 64% decrease in nonfatal PE or VTE-related death in patients treated with semuloparin compared with placebo without significant increase in bleeding complications.[80]

Apixaban and rivaroxaban are both oral direct anti-factor Xa inhibitors. In a recent Phase II study of use of apixaban for VTE prophylaxis in patients with metastatic cancer, apixaban was well tolerated and not associated with increased risk of bleeding.[86] The MAGELLAN trial, which is currently underway, is evaluating extended therapy with oral rivaroxaban in patients hospitalized for acute illness of whom 7.3% have active cancer. Standard-duration enoxaparin (~10 days) will be compared with standard- and extended-duration (~5 weeks) in VTE prophylaxis.[87]

LMWH is still the treatment of choice for cancer-related VTE. LMWH preparations are not all alike, however, and some lack evidence for superiority over oral VKAs. We eagerly await the results of ongoing clinical trials aimed at better identifying patient subgroups that merit prophylactic anticoagulation, at determining the optimal duration and type of anticoagulation in this group and at assessing the appropriateness of the new oral anticoagulants among patients with malignancies. Oral factor Xa inhibitors in clinical trials of VTE treatment and prophylaxis enrolled only a limited number of patients with active cancer. They do show promise regarding their efficacy and safety, but need to be more extensively studied in cancer-related VTE-specific trials. However, their cost may be an important limiting factor in their widespread use.

The risk model developed by Khorana et al. utilizes easily obtained variables to identify high-risk patients and the results of an ongoing trial are anticipated to determine whether instituting prophylactic antithrombotic therapy in such patients is safe and effective. Also, additional biomarkers such as plasma D-dimer, sP-selectin and/or plasma tissue factor may provide additional criteria to select very high risk cancer patients.

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