A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment - Impact on survival and bleeding complications

BACKGROUND. Preclinical evidence Suggests that anticoagulants, in particular the low-molecular-weight heparins (LMWH), exert an antitumor effect, whereas clini cal trials have reported conflicting results. The authors conducted a comprehen sive, systematic review and meta-analysis of the evidence from randomized controlled trials (RCTs), to evaluate the impact of anticoagulants oil survival and safety in cancer patients without venous thromboembolisro. METHODS. A comprehensive systematic literature review of RCTs was performed ester. New York. without language restrictions through May 2006 with subsequent updates to the end of 2006, including an exhaustive search of electronic databases, major conference proceedings, article references, and content experts. Two reviewers extracted data independently Primary study outcomes were I-year overall mortality and all bleeding complications. Major and fatal bleeding complications Supported in part by the American Society of were secondary outcomes. Clinical Oncology. RESULTS. Across all I I studies that were identified, anticoagulation significantly decreased 1-year overall mortality with a relative risk (1111) of 0.905 (95% confi Or Khorana is deuce interval [95% CI], 0.847-0.967; P =.003). The RR for mortalitV was 0.877 (95% Cl, 0.789-0.975; P =.015) for LMWH, compared with an RR of 0.942 (95% Cl, 0.854-1.040; P =.239) for warfarm, resulting in an absolute risk difference Dr. Khorana has previously received research (ARD) of 8% for LMWH and an ARD of 3% for warfarin. Improved Survival with anticoagulation may be dependent on tumor type. Major bleeding episodes Aventis. Occurred less frequently in patients who received LMWH (ARD, 1%) compared with patients who received warfarin (ARD, 11.5%; P <.0001). Overall, fatal bleed-Dr. ing occurred rarely (ARD, 0.32%; P =.542). 11 funding from Pfizer and consultant fee and honoraria CONCLUSIONS. Anticoagulants, particularly I_MwH, significantly improved overall survival in cancer patients without venous thrombosis while increasing the risk Presented in part at the American Society of for bleeding complications. However, given the limitations of available data, the Clinical Oncology Venous Thrombosis Guideline use of anticoagUlants as antineoplastic therapy cannot be recommended until Committee Meeting, Alexandria, VA, July 2006. additional RCTs confirm these results. Cancer 2007;110:1149-61. (D 2007American We thank the expert panel of the Venous Thrombo- CancerSocietj