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REVIEW ARTICLE

Low-molecular-weight heparins and cancer: Focus on antitumoral effect

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Pages 116-121 | Received 06 Nov 2014, Accepted 18 Dec 2014, Published online: 13 Mar 2015

References

  • Trousseau A. Phlegmasia alba dolens. In: Trousseau A, editor. Clinique medicinale de l’Hotel-Dieu de Paris. Paris: Bailliere J.-B. et fils; 1865. p. 645–712.
  • Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case–control study. Arch Intern Med. 2000;160:809–15.
  • Heit JA, O’Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med. 2002;162:1245–8.
  • Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol. 2005;128:291–302.
  • Prandoni P, Lensing AW, Buller HR, Cogo A, Prins MH, Cattelan AM, et al. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med. 1992;327:1128–33.
  • Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100:3484–8.
  • Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000;343: 1846–50.
  • Chee CE, Ashrani AA, Marks RS, Petterson TM, Bailey KR, Melton LJ 3rd, et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study. Blood. 2014;123:3972–8.
  • Franchini M, Montagnana M, Favaloro EJ, Lippi G. The bidirectional relationship of cancer and hemostasis and the potential role of anticoagulant therapy in moderating thrombosis and cancer spread. Semin Thromb Hemost. 2009;35:644–53.
  • Franchini M, Mannucci PM. Thrombin and cancer: from molecular basis to therapeutic implications. Semin Thromb Hemost. 2012;38: 95–101.
  • Lee AY, Peterson EA. Treatment of cancer-associated thrombosis. Blood. 2013;122:2310–17.
  • Kher A, Samama MM. Primary and secondary prophylaxis of venous thromboembolism with low-molecular-weight heparins: prolonged thromboprophylaxis, an alternative to vitamin K antagonists. J Thromb Haemost. 2005;3:473–81.
  • Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, et al.;American Society of Clinical Oncology Clinical Practice. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2189–204.
  • Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost. 2013;11:56–70.
  • Hull RD, Townshend G. Long-term treatment of deep-vein thrombosis with low-molecular-weight heparin: an update of the evidence. Thromb Haemost. 2013;110:14–22.
  • Barsam SJ, Patel R, Arya R. Anticoagulation for prevention and treatment of cancer-related venous thromboembolism. Br J Haematol. 2013;161:764–77.
  • Gary T. Cancer related venous thromboembolism – prophylaxis and therapy. Vasa. 2014;43:245–51.
  • Noble S. Heparin and cancer survival: where do we stand? Thromb Res. 2014;133(Suppl 2):S133–8.
  • Cunningham MS, Preston RJS, O’Donnell JS. Does antithrombotic therapy improve survival in cancer patients? Blood Rev. 2009;23: 129–35.
  • Albert-Weil J, Nehorias J. Two cases of neoplasms not justified for classical therapy, treated with intravenous injections of heparin and intramuscular injections of leech extracts. Rev Pathol Gen Physiol Clin. 1954;54:1014–20.
  • Niers TM, Klerk CP, DiNisio M, Van Noorden CJ, Büller HR, Reitsma PH, et al. Mechanisms of heparin induced anti-cancer activity in experimental cancer models. Crit Rev Oncol Hematol. 2007; 61:195–207.
  • Dolovich LR, Ginsberg JS, Douketis JD, Holbrook AM, Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med. 2000;160:181–8.
  • Hu L, Lee M, Campbell W, Perez-Soler R, Karpatkin S. Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis. Blood. 2004;104:2746–51.
  • Mousa SA, Petersen LJ. Anti-cancer properties of low-molecular-weight heparin: preclinical evidence. Thromb Haemost. 2009;102:258–67.
  • Smiley SL, Henry DO, Wong MK. The mechanism of low molecular weight heparin (LMWH) inhibition of tumor growth. J Clin Oncol. 2006;24:18S.
  • Takeuchi A, Yamamoto Y, Munesue S, Harashima A, Watanabe T, Yonekura H, et al. Low molecular weight heparin suppresses receptor for advanced glycation end products-mediated expression of malignant phenotype in human fibrosarcoma cells. Cancer Sci. 2013;104:740–9.
  • Balzarotti M, Fontana F, Marras C, Boiardi A, Croci D, Ciusani E, et al. In vitro study of low molecular weight heparin effect on cell growth and cell invasion in primary cell cultures of high-grade gliomas. Oncol Res. 2006;16:245–50.
  • Takahashi H, Ebihara S, Okazaki T, Asada M, Sasaki H, Yamaya M. A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol. 2005;146:333–43.
  • Bereczky B, Gilly R, Rásó E, Vágó A, Tímár J, Tóvári J. Selective antimetastatic effect of heparins in preclinical human melanoma models is based on inhibition of migration and microvascular arrest. Clin Exp Metastasis. 2005;22:69–76.
  • Mousa SA, Johansen KB. Anti-cancer efficacy of low molecular weight heparin in thrombosis-associated tumor growth. J Thromb Haemost. 2007;5 (Suppl 2): P-M-525.
  • Pross M, Lippert H, Misselwitz F, Nestler G, Krüger S, Langer H, et al. Low-molecular-weight heparin (reviparin) diminishes tumor cell adhesion and invasion in vitro, and decreases intraperitoneal growth of colonadeno-carcinoma cells in rats after laparoscopy. Thromb Res. 2003;110:215–20.
  • Pross M, Lippert H, Nestler G, Kuhn R, Langer H, Mantke R, et al. Effect of low molecular weight heparin on intra-abdominal metastasis in a laparoscopic experimental study. Int J Colorectal Dis. 2004;19:143–6.
  • Amirkhosravi A, Mousa SA, Amaya M, Francis JL. Antimetastatic effect of tinzaparin, a low-molecular-weight heparin. J Thromb Haemost. 2003;1:1972–6.
  • Szende B, Paku S, Rácz G, Kopper L. Effect of Fraxiparine and heparin on experimental tumor metastasis in mice. Anticancer Res. 2005, 25:2869–72.
  • Ludwig RJ, Alban S, Bistrian R, Boehncke WH, Kaufmann R, Henschler R, et al. The ability of different forms of heparins to suppress P-selectin function in vitro correlates to their inhibitory capacity on bloodborne metastasis in vivo. Thromb Haemost. 2006;95:535–40.
  • Stevenson JL, Choi SH, Varki A. Differential metastasis inhibition by clinically relevant levels of heparins—correlation with selectin inhibition, not antithrombotic activity. Clin Cancer Res. 2005;11: 7003–11.
  • Harvey JR, Mellor P, Eldaly H, Lennard TW, Kirby JA, Ali S. Inhibition of CXCR4-mediated breast cancer metastasis: a potential role for heparinoids? Clin Cancer Res. 2007;13:1562–70.
  • Mousa SA, Linhardt R, Francis JL, Amirkhosravi A. Anti-metastatic effect of a nonanticoagulant low-molecular-weight heparin versus the standard low-molecular-weight heparin, enoxaparin. Thromb Haemost. 2006;96:816–21.
  • Stevenson JL, Varki A, Borsig L. Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but nonanticoagulant heparins can have additional effects. Thromb Res. 2007;120(Suppl 2): S107–11.
  • Norrby K. Low-molecular-weight heparins and angiogenesis. APMIS. 2006;114:79–102.
  • Mousa SA, Mohamed S. Inhibition of endothelial cell tube formation by the low molecular weight heparin, tinzaparin, is mediated by tissue factor pathway inhibitor. Thromb Haemost. 2004;92:627–33.
  • Collen A, Smorenburg SM, Peters E, Lupu F, Koolwijk P, Van Noorden C, et al. Unfractionated and low molecular weight heparin affect fibrin structure and angiogenesis in vitro. Cancer Res. 2000;60:6196–200.
  • Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Low molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146–53.
  • 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-molecular-weight heparin in small cell lung cancer. J Thromb Haemost. 2004;2:1266–71.
  • 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;22:1944–8.
  • 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; 23:2130–5.
  • Sideras K, Schaefer PL, Okuno SH, Sloan JA, Kutteh L, Fitch TR, et al. Low-molecular-weight heparin in patients with advanced cancer: a phase 3 clinical trial. Mayo Clin Proc. 2006;81:758–67.
  • Agnelli G, Gussoni G, Bianchini C, Verso M, Mandalà M, Cavanna L, et al.; PROTECHT Investigators. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo controlled, double-blind study. J Lancet Oncol. 2009;10:943–9.
  • van Doormaal FF, Di Nisio M, Otten HM, Richel DJ, Prins M, Buller HR. Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol. 2011;29:2071–6.
  • Perry JR, Julian JA, Laperriere NJ, Geerts W, Agnelli G, Rogers LR, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost. 2010;8: 1959–65.
  • Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, et al.; SAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012; 366:601–9.
  • Haas SK, Freund M, Heigener D, Heilmann L, Kemkes-Matthes B, von Tempelhoff GF, et al.; TOPIC Investigators. Low-molecular-weight heparin versus placebo for the prevention of venous thromboembolism in metastatic breast cancer or stage III/IV lung cancer. Clin Appl Thromb Hemost. 2012;18:159–65.
  • Maraveyas A, Waters J, Roy R, Fyfe D, Propper D, Lofts F, et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer. 2012;48:1283–92.
  • Lecumberri R, López Vivanco G, Font A, González Billalabeitia E, Gúrpide A, Gómez Codina J, et al. Adjuvant therapy with bemiparin in patients with limited-stage small cell lung cancer: results from the ABEL study. Thromb Res. 2013;132:666–70.
  • Meyer G, Besse B, Friard S, Girard P, Corbi P, Azarian R, et al. Effect of tinzaparin on survival in non-small-cell lung cancer after surgery. TILT: tinzparin in lung tumours. Rev Mal Respir. 2011; 28:654–9.
  • Griffith GO, Burns S, Noble SI, Macbeth FR, Cohen D, Maughan TS. FRAGMATIC: a randomized phase III clinical trial investigating the effect of fragmin added to standard therapy in patients with lung cancer. BMC Cancer. 2009;9:355.
  • Kuderer NM, Khorana AA, Lyman GH, Francis CW. A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment: impact on survival and bleeding complications. Cancer. 2007;110:1149–61.
  • Lazo-Langner A, Goss GD, Spaans JN, Rodger MA. The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J Thromb Haemost. 2007; 5:729–37.
  • Sanford D, Naidu A, Alizadeh N, Lazo-Langner A. The effect of low molecular weight heparin on survival in cancer patients: an updated systematic review and meta-analysis of randomized trials. J Thromb Haemost. 2014;12:1076–85.
  • Che DH, Cao JY, Shang LH, Man YC, Yu Y. The efficacy and safety of low-molecular-weight heparin use for cancer treatment: a meta-analysis. Eur J Intern Med. 2013;24:433–9.
  • Akl EA, Gunukula S, Barba M, Yosuico VE, van Doormaal FF, Kuipers S, et al. Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev. 2011;4: CD006652.
  • Rada G, Schünemann HJ, Labedi N, El-Hachem P, Kairouz VF, Akl EA. Systematic evaluation of the methodology of randomized controlled trials of anticoagulation in patients with cancer. BMC Cancer. 2013; 13:76.
  • Gerotziafas GT, Papageorgiou C, Hatmi M, Samama MM, Elalamy I. Clinical studies with anticoagulants to improve survival in cancer patients. Pathophysiol Haemost Thromb. 2008;36:204–11.

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