Anticoagulants and Cancer Survival

ABSTRACT

The association between cancer and activation of blood coagulation has been described since Trousseau's time. The hypercoagulable state often encountered in cancer patients not only acts as an important risk factor for thrombosis, but also may play a role in tumor progression and metastasization. An antineoplastic effect of anticoagulants in this setting has often been hypothesized. The results of recently conducted clinical trials suggest that cancer patients could have a benefit from administration of low molecular weight heparin, particularly in those with nonadvanced disease. Additional clinical trials are needed to provide an important step forward in this challenging setting.

Cancer - venous thromboembolism (VTE) - low molecular weight heparins (LMWH) - anticoagulant agents - survival

REFERENCES

• 1 Trousseau A. Phlegmasia alba dolens. In: Clinique Medicale de l'Hotel-Dieu de Paris. London; The New Sydenham Society 1865: 94-96
• 2 Falanga A, Piccioli A. Effects of anticoagulant drugs in cancer.  Curr Opin Pulm Med. 2005;  11 403-407
• 3 Rickles F R, Falanga A. Molecular basis for the relationship between thrombosis and cancer.  Thromb Res. 2001;  102 V215-V224
• 4 Yu J Y, May L, Lhotak V et al.. Oncogenic events regulating tissue factor expression.  Haematologica Reports. 2005;  1(9) 18-20
• 5 Boccaccio C, Sabatino C, Medico E et al.. The MET oncogene driver a genetic programme linking cancer to haemostasis.  Nature. 2005;  434 396-400
• 6 Michaels L. Cancer incidence and mortality in patients having anticoagulant therapy.  Lancet. 1964;  22 832-835
• 7 Zacharski L R, Henderson W G, Rickles F R et al.. Effect of warfarin on survival in small cell carcinoma of the lung.  JAMA. 1981;  245 831-835
• 8 Smorenburg S M, Vink R, Otten H M et al.. The effect of vitamin K antagonists on survival of patients with malignancy: a systematic analysis.  Thromb Haemost. 2001;  86 1586-1587
• 9 Zacharski L R, Ornstein D L. Haparin and cancer.  Thromb Haemost. 1998;  80 10-23
• 10 Lebeau B, Chastang C, Brechot J M et al.. Subcutaneous heparin treatment increases survival in small cell lung cancer.  Cancer. 1994;  74 38-44
• 11 Smorenburg S M, Hettiarachchi R J, Vink R et al.. The effects of unfractionated heparin on survival in patients with malignancy-a systematic review.  Thromb Haemost. 1999;  82 1600-1604
• 12 Hettiarachchi R J, Smorenburg S M, Ginsberg J et al.. Do heparins do more than just treat thrombosis? The influence of heparin on cancer spread.  Thromb Haemost. 1999;  82 947-952
• 13 Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg J S. Low-molecular-weight heparin and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis.  Am J Med. 1996;  100 269-277
• 14 Wojtukiewicz M Z, Kozlowski L, Ostrowska K et al.. Low-molecular-weight heparin treatment for malignant melanoma: a pilot clinical trial.  Thromb Haemost. 2003;  89 405-406
• 15 Kakkar A K, Levine M N, Kadziola Z et al.. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the Fragmin advanced malignancy outcome study (FAMOUS).  J Clin Oncol. 2004;  22 1944-1948
• 16 Altinbas M, Coskun H S, Er O et al.. A randomized clinical trial of combination chemotherapy with and without low molecular weight heparin in small cell lung cancer.  J Thromb Haemost. 2004;  2 1266-1271
• 17 Klerk C P, Smorenburg S M, Otten H M et al.. The effect of low molecular weight heparin on survival in patients with advanced malignancy.  J Clin Oncol. 2005;  23 2130-2135
• 18 Lee A Y, Rickles F R, Julian J A et al.. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.  J Clin Oncol. 2005;  23 2123-2129
• 19 Lee A Y, Levine M N, Baker R I et al.. Comparison of low molecular weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.  N Engl J Med. 2003;  349 146-153