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The effect of low molecular weight heparin on survival in patients with cancer

Year 2006, Volume: 21 Issue: 1, 42 - 46, 01.02.2006

Mert Saynak Vuslat Yürüt Çaloğlu Gülden Bayır Murat Çaloğlu Cem Uzal

Abstract

The association between cancer and venous thromboembolism (VTE) is well established. Of all new venous tromboembolism, approximately 20% are associated with active malignancy. In these cases, the pathogenic mechanisms of thrombosis involve a complex interaction between tumour cells, the haemostatic system, and charateristics of the patient. Anticoagulants are the mainstay therapy for the prevention and treatment of acute VTE. The natural history of VTE is more agressive and anticoagulant treatment failure is more frequent in cancer patients than in patients without cancer. Recently, the results of new prospective randomized clinical trials to evaluate the effect of low-molecular-weight heparin on cancer survival have become available. The results suggest a benefit from treatment, particularly in patients with nonadvanced disease. However, these results are not conclusive and require further research.

Keywords

Heparin Low-Molecular-Weight Neoplasms Anticoagulants Survival Analysis Venous Thrombosis Thromboembolism

References

  • 1. Deitcher SR. Cancer-related deep venous thrombosis: clinical importance, treatment challenges, and management strategies. Semin Thromb Hemost 2003;29(3):247-58.
  • 2. Kroger K, Weiland D, Ose C, Neumann N, Weiss S, Hirsch C, et al. Risk factors for venous thromboembolic events in cancer patients. Ann Oncol 2006;17(2):297-303.
  • 3. Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000;343(25):1846-50.
  • 4. Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK, 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(10):1944-8.
  • 5. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Randomized Comparison of LowMolecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Ve n o u s Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003;349(2):146-53.
  • 6. Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A, et al. A randomized clinical trial of combination chemotherapy with and without low-molecularweight heparin in small cell lung cancer. J Thromb Haemost 2004;2(8):1266-71.
  • 7. Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 2005;23(10):2130-5.
  • 8. Green D, Hull RD, Brant R, Pineo GF. Lower mortality in cancer patients treated with low-molecularweight versus standard heparin. Lancet 1992;339(8807):1476.
  • 9. Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg JS. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 1996;100(3):269-77.
  • 10. Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 1999;130(10):800-9.
  • 11. Hettiarachchi RJ, Smorenburg SM, Ginsberg J, Levine M, Prins MH, Buller HR. Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread. Thromb Haemost 1999;82(2):947-52.
  • 12. Kakkar AK, Levine MN. Thrombosis and cancer: implications beyond Trousseau. J Thromb Haemost 2004;2(8):1261-2.
  • 13. Kakkar AK, Lemoine NR, Scully MF, Tebbutt S, Williamson RC. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995;82(8):1101-4.
  • 14. Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998;140(5):1241-53.
  • 15. Folkman J, Weisz PB, Joullie MM, Li WW, Ewing WR. Control of angiogenesis with synthetic heparin subtitutes. Science 1989;243(4897):1490-3.
  • 16. Hasan J, Shnyder SD, Clamp AR, McGown AT, Bicknell R, Presta M, et al. Heparin octasaccharides inhibit angiogenesis in vivo. Clin Cancer Res 2005;11(22):8172-9.
  • 17. Nasir FA, Patel HK, Scully MF, et al. The low molecular weight heparin dalteparin sodium inhibits angiogenesis and induces apoptosis in an experimental tumour model. Blood 2003;102(11). [Abstract] (Presented at the American Society of Hematology 45th Annual Meeting; December 6-9, 2003; San Diego, USA).
  • 18.Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci U S A 2001;98(6):3352-7.
  • 19. Miller GJ, Bauer KA, Howarth DJ, Cooper JA, Humphries SE, Rosenberg RD. Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway. J Thromb Haemost 2004;2(12):2107-14.
  • 20. Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial. N Engl J Med 2000;342(26):1953-8.
  • 21. Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):338S-400S.
  • 22.Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease. (The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy) Chest 2004;126:401S-428S.

Kanser hastalarında düşük molekül ağırlıklı heparin'in sağkalım üzerine etkisi

Year 2006, Volume: 21 Issue: 1, 42 - 46, 01.02.2006

Mert Saynak Vuslat Yürüt Çaloğlu Gülden Bayır Murat Çaloğlu Cem Uzal

Abstract

Kanser ile venöz tromboemboli (VTE) gelişimi arasında iyi bilinen bir ilişki vardır. Yeni tanı alan tromboembolizm olgularının yaklaşık %20 kadarının malign hastalıkla ilişkili olduğu görülmektedir. Trombozun patogenezinde ise tümör hücreleri, homeostatik sistem ve hasta özellikleri arasındaki kompleks ilişkiler sorumlu tutulmaktadır. Akut VTE'nin önlenmesinde ve tedavisinde başlıca dayanak antikoagülanlardır. Kanser hastalarında hastalık daha kötü seyretmekte ve sıklıkla tedaviler yanıtsız kalabilmektedir. Son dönemlerde kanser hastalarında düşük molekül ağırlıklı heparinin (DMAH) sağkalım üzerine etkisini değerlendiren randomize çalışmalarda özellikle hastalığı ilerlememiş hastaların tedaviden faydalandığı gösterilmektedir. Bununla birlikte sonuçlar tartışmalıdır ve yeni çalışmalara ihtiyaç duyulmaktadır.

Keywords

Antikoagülan/yan etki heparin düşük molekül ağırlıklı neoplazi/komplikasyon/ilaç tedavisi sağkalım araştırması venöz tromboz/ilaç tedavisi/etyoloji

References

  • 1. Deitcher SR. Cancer-related deep venous thrombosis: clinical importance, treatment challenges, and management strategies. Semin Thromb Hemost 2003;29(3):247-58.
  • 2. Kroger K, Weiland D, Ose C, Neumann N, Weiss S, Hirsch C, et al. Risk factors for venous thromboembolic events in cancer patients. Ann Oncol 2006;17(2):297-303.
  • 3. Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000;343(25):1846-50.
  • 4. Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK, 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(10):1944-8.
  • 5. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Randomized Comparison of LowMolecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Ve n o u s Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003;349(2):146-53.
  • 6. Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A, et al. A randomized clinical trial of combination chemotherapy with and without low-molecularweight heparin in small cell lung cancer. J Thromb Haemost 2004;2(8):1266-71.
  • 7. Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 2005;23(10):2130-5.
  • 8. Green D, Hull RD, Brant R, Pineo GF. Lower mortality in cancer patients treated with low-molecularweight versus standard heparin. Lancet 1992;339(8807):1476.
  • 9. Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg JS. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 1996;100(3):269-77.
  • 10. Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 1999;130(10):800-9.
  • 11. Hettiarachchi RJ, Smorenburg SM, Ginsberg J, Levine M, Prins MH, Buller HR. Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread. Thromb Haemost 1999;82(2):947-52.
  • 12. Kakkar AK, Levine MN. Thrombosis and cancer: implications beyond Trousseau. J Thromb Haemost 2004;2(8):1261-2.
  • 13. Kakkar AK, Lemoine NR, Scully MF, Tebbutt S, Williamson RC. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995;82(8):1101-4.
  • 14. Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998;140(5):1241-53.
  • 15. Folkman J, Weisz PB, Joullie MM, Li WW, Ewing WR. Control of angiogenesis with synthetic heparin subtitutes. Science 1989;243(4897):1490-3.
  • 16. Hasan J, Shnyder SD, Clamp AR, McGown AT, Bicknell R, Presta M, et al. Heparin octasaccharides inhibit angiogenesis in vivo. Clin Cancer Res 2005;11(22):8172-9.
  • 17. Nasir FA, Patel HK, Scully MF, et al. The low molecular weight heparin dalteparin sodium inhibits angiogenesis and induces apoptosis in an experimental tumour model. Blood 2003;102(11). [Abstract] (Presented at the American Society of Hematology 45th Annual Meeting; December 6-9, 2003; San Diego, USA).
  • 18.Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci U S A 2001;98(6):3352-7.
  • 19. Miller GJ, Bauer KA, Howarth DJ, Cooper JA, Humphries SE, Rosenberg RD. Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway. J Thromb Haemost 2004;2(12):2107-14.
  • 20. Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of Anticoagulation Trial. N Engl J Med 2000;342(26):1953-8.
  • 21. Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):338S-400S.
  • 22.Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease. (The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy) Chest 2004;126:401S-428S.
There are 22 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Mert Saynak This is me

Vuslat Yürüt Çaloğlu This is me

Gülden Bayır This is me

Murat Çaloğlu This is me

Cem Uzal This is me

Publication Date February 1, 2006
Published in Issue Year 2006 Volume: 21 Issue: 1

Cite

APA Saynak, M., Çaloğlu, V. Y., Bayır, G., Çaloğlu, M., et al. (2006). Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine etkisi. Türk Onkoloji Dergisi, 21(1), 42-46.
AMA Saynak M, Çaloğlu VY, Bayır G, Çaloğlu M, Uzal C. Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine etkisi. Türk Onkoloji Dergisi. February 2006;21(1):42-46.
Chicago Saynak, Mert, Vuslat Yürüt Çaloğlu, Gülden Bayır, Murat Çaloğlu, and Cem Uzal. “Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine Etkisi”. Türk Onkoloji Dergisi 21, no. 1 (February 2006): 42-46.
EndNote Saynak M, Çaloğlu VY, Bayır G, Çaloğlu M, Uzal C (February 1, 2006) Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine etkisi. Türk Onkoloji Dergisi 21 1 42–46.
IEEE M. Saynak, V. Y. Çaloğlu, G. Bayır, M. Çaloğlu, and C. Uzal, “Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine etkisi”, Türk Onkoloji Dergisi, vol. 21, no. 1, pp. 42–46, 2006.
ISNAD Saynak, Mert et al. “Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine Etkisi”. Türk Onkoloji Dergisi 21/1 (February 2006), 42-46.
JAMA Saynak M, Çaloğlu VY, Bayır G, Çaloğlu M, Uzal C. Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine etkisi. Türk Onkoloji Dergisi. 2006;21:42–46.
MLA Saynak, Mert et al. “Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine Etkisi”. Türk Onkoloji Dergisi, vol. 21, no. 1, 2006, pp. 42-46.
Vancouver Saynak M, Çaloğlu VY, Bayır G, Çaloğlu M, Uzal C. Kanser hastalarında düşük molekül ağırlıklı heparin’in sağkalım üzerine etkisi. Türk Onkoloji Dergisi. 2006;21(1):42-6.