Annals of Oncology Advance Access originally published online on May 2, 2006
Annals of Oncology 2006 17(10):1604-1606; doi:10.1093/annonc/mdl092
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© 2006 European Society for Medical Oncology
letters to the editor |
Does low-molecular-weight heparin influence cancer-related mortality?
1 Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy
2 Biostatistics Unit, Regina Elena Cancer Institute, Rome, Italy
3 Division of Medical Oncology, Treviglio Hospital, Treviglio (Bergamo), Italy
*(E-mail: gia.fer{at}flashnet.it)
In a large multicenter prospective trial [1], in which 672 cancer patients were randomly assigned to receive LMWH or oral anticoagulant therapy (OAT) for 6 months, a statistically significant improvement in overall survival (death for any cause at 12 months) in favor of dalteparin over OAT was demonstrated in patients affected by non-metastatic disease (hazard ratio, 0.50; 95% CI, 0.27–0.95; P = 0.03) [2]. These authors used all-cause mortality rather than cancer-related mortality. For this reason, we performed a literature-based pooled analysis to summarize the results of the randomized trials concerning cancer-related death during anticoagulant therapy and follow-up in cancer patients receiving LWMH or OAT (Table 1). Event-based relative risk (RR) ratios with 95% CIs were derived. Combined-effect estimation was computed with both random- and fixed-effect models. A heterogeneity test was applied as well.
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Concerning cancer-related death, we selected eight studies [1, 3–9] to evaluate the incidence of cancer-related mortality during treatment and follow up in cancer patients by type of anticoagulant therapy. We considered only cancer patients, according to the data reported in a pooled-analysis of 1726 patients [10]. Our previously reported results [11] were based on data extracted from a prior meta-analysis [12]. No significant difference in cancer mortality was observed between the two treatment modalities: (RR 0.97; 95% CI 0.81–1.15; P = 0.75) (Figure 1). The test for heterogeneity was not significant (P = 0.97).
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Conversely, we selected seven studies [3–8, 13] that recruited patients with and without cancer in order to evaluate the incidence of overall mortality during treatment and follow up by type of anticoagulant therapy. No significant difference was registered: a total of 15 of 495 patients (3%) in the LMWH group died versus 12 of 607 patients (1.9%) in the OAT group, with a non-significant reduction of the risk of recurrent symptomatic VTE in favor OAT (RR 1.38; 95% CI 0.63–3.00; P = 0.41). The test for heterogeneity was not significant (P = 0.78).
No difference was observed applying both the fixed- and the random-effect model.
None of these studies was primarily designed to investigate the effect of LMWH or OAT on cancer-related mortality, because the primary question in many of them was addressing recurrent VTE. The pitfalls of this type of analysis, including the concept of combining different cancers at different stages and biologic activity, and the discrepancies among studies in anticoagulant therapy dosage and duration must be taken into account: the CLOT trial [1] reported on the mortality of patients treated for 6 months, whereas the other studies treated patients for 3–6 months [3–9, 13]. Moreover, when Lee et al. [2] separated out the good prognosis cancer patients, a statistically significant difference in mortality was seen at 1 year.
However, the absence of a significant heterogeneity (P = 0.97) suggests the consistency of these results. Thus, the putative antineoplastic effect exerted by LMWH in cancer patients remains still controversial. Further large clinical trials still need to be run in order to address this fascinating issue.
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 Top References |
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1. Lee AY, Levine MN, Baker RI, et al. (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:2146–153.
2. Lee AY, Rickles FR, Julian JA, et al. (2005) Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thrombo-embolism. J Clin Oncol 23:102123–2129.
3. Pini M, Aiello S, Manotti C, et al. (1994) Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thromb Haemost 72:2191–197.[Web of Science][Medline]
4. Das SK, Cohen AT, Edmondson RA, et al. (1996) Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial. World J Surg 20:521–526.[CrossRef][Web of Science][Medline]
5. Gonzalez-Fajardo JA, Arreba E, Castrodeza J, et al. (1999) Venographic comparison of subcutaneous low-molecular-weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis. J Vasc Surg 30:283–290.[CrossRef][Web of Science][Medline]
6. Lopaciuk S, Bielska-Falda H, Noszczyk W, et al. (1999) Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis. Thromb Haemost 81:26–31.[Web of Science][Medline]
7. Veiga F, Escriba A, Maluenda MP, et al. (2000) Low-molecular weight heparin (Enoxaparin) versus oral anticoagulant therapy (Acenocumarol) in the long-term treatment of deep venous thrombosis in the elderly: a randomized trial. Thromb Haemost 84:559–564.[Web of Science][Medline]
8. Lopez-Beret P, Orgaz A, Fontcuberta J, et al. (2001) Low-molecular weight heparin versus oral anticoagulant in the long-term treatment of deep venous thrombosis. J Vasc Surg 33:77–90.[Web of Science][Medline]
9. Meyer G, Marjanovic Z, Valcke J, et al. (2002) Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med 162:151729–1735.
10. Conti S, Guercini F, Iorio A. (2003) Low-molecular-weight heparin and cancer survival: review of the literature and pooled analysis of 1,726 patients treated for at least three months. Pathophysiol Haemost Thromb 33:4197–201 Jul-2004.[CrossRef][Medline]
11. Ferretti G, Bria E, Giannarelli D, et al. (2005) Low-molecular-weight heparin versus oral anticoagulant therapy for the long-term treatment of symptomatic venous thromboembolism: no difference in cancer-related mortality. J Clin Oncol 23:287248–7250.
12. Iorio A, Guercini F, Pini M. (2003) Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants. J Thromb Haemost 1:91906–1913.[CrossRef][Web of Science][Medline]
13. Kakkar VV, Gebska M, Kadziola Z, et al. (2003) Low-molecular-weight heparin in the acute and long-term treatment of deep vein thrombosis. Thromb Haemost 89:4674–680.[Web of Science][Medline]
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  G Meyer Does low-molecular-weight heparin influence cancer-related mortality? Ann. Onc., March 1, 2007; 18(3): 609 - 610. [Full Text] [PDF]
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