Does Anti-coagulation Improve Results in Cancer?

Should heparin be offered to patients with cancer who have no standard indication for anticoagulation therapy? Patients with advanced cancer, especially patients undergoing chemotherapy, commonly experience venous thromboembolism (VTE), such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Consequences of venous thromboembolism include higher morbidity, hospitalization, interruption of chemotherapy, initiation of anticoagulant therapy or insertion of a vena cava filter, decreased quality of life, increased medical costs, and increased mortality.1,2 The current issue of Heme-O-Gram reviews a recent NEJM report and editorial on the potential improvement in outcomes that may be brought about by use of low molecular weight heparin (LMWH). Semuloparin Reduces Venous Thromboembolism in Cancer Patients In the SAVE-ONCO study, a multi-center double-blinded trial of 3,212 adult patients with locally advanced or metastatic cancer of various representative types who were undergoing chemotherapy patients were randomized to receive daily subcutaneous injections of either 20 mg of semuloparin, a semisynthetic, ultra-LMWH, or placebo for a median duration of 3.5 months. The treatment arm had significantly lowered incidence of venous thromboembolism (including DVT and fatal and non-fatal PE) without significantly increased major bleeding. However, the anticoagulant did not lower the mortality rate, as the rate of death in the semuloparin and placebo group was 43.4% and 44.5%, respectively.1 Pooled Analysis of Clinical Studies of Anticoagulation for Cancer Patients In the accompanying NEJM editorial on the SAVE-ONCO study, Aki and Schunemann analysed data pooled from the SAVE-ONCO study, their prior Cochrane systematic review of studies with LMWH, and another clinical trial. Using this pooled data approach of several studies they concluded that a year of treatment with LMWH in 1,000 patients with advanced cancer would result in no significant rise in major bleeding, 20 fewer thromboembolic events (and a decrease in related hospitalizations), and approximately 30 fewer deaths. The reduction in mortality was something that the SAVE-ONCO study was not strongly powered enough to demonstrate. Intriguing Mechanisms of Action of Heparins Heparins theoretically may have anti-tumor effects (including inhibiting cell to cell interactions, activity of extracellular matrix enzymes, and angiogenesis), in addition to direct anticoagulant effects.2 Antithrombotic drugs may counteract the prothrombotic effects of chemotherapy.1 Future Directions for Anticoagulant Use in Cancer Patients At the present time, guidelines recommend that cancer patients who have been hospitalized for medical illness or have undergone surgery for cancer should receive prophylaxis with anticoagulants. Given the results of the clinical studies of LMWH, stratification of risk for VTE among cancer patients, including ambulatory patients receiving chemotherapy, may be helpful.1 Ongoing and future trials may reveal whether patients with particular types and stages of solid tumors will obtain improved tumor response, quality-of-life benefits, and survival extension from adjuvant anticoagulant therapy.2 For more discussion, please visit the following URLs and links: 1 http://www.nejm.org/doi/full/10.1056/NEJMoa1108898 2 http://www.nejm.org/doi/full/10.1056/NEJMe1113672 E Thanks to everyone who has sent me feedback. Feel free to email me, or post your own comments. Stanford University