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Journal of Clinical Oncology, Vol 23, No 28 (October 1), 2005: pp. 7250 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.02.1527
In Reply:McMaster University, Henderson Research Centre, Hamilton, Ontario, Canada; St Bartholomew's and the London Hospitals Medical School, London, England Ferretti et al state that patients with malignancy and venous thromboembolism (VTE) treated with oral anticoagulant therapy "possibly" have an increased risk of recurrent VTE compared with patients without malignancy. The literature is consistent that cancer patients with acute VTE who are treated with long-term oral anticoagulant therapy have an increased risk of recurrent VTE compared with those without cancer.1,2 They are also somewhat tentative concerning secondary prophylaxis with low-molecular-weight heparin (LMWH). The results of the trial by Lee et al, which compared long-term dalteparin LMWH with oral anticoagulant therapy in cancer patients with acute VTE demonstrated a 52% relative reduction in recurrent thromboembolism in favor of LMWH, which was highly statistically significant.3 They make the point that in our recent report, we used all-cause mortality rather than cancer-related mortality.4 The convention in randomized trials in oncology is generally to report all-cause mortality. In our trial, two thirds of the patients who presented with acute VTE had metastatic disease. At 6 months, 90% of the deaths were related to progressive cancer.3 Hence, it is reasonable to assume that at 1 year, most of the deaths were cancer related. In their analysis, they pooled the results of two randomized trials that specifically compared oral anticoagulant therapy with LMWH in cancer patients, plus the results of a meta-analysis of trials that included cancer patients and those without cancer. We question whether a meta-analysis is appropriate. These trials differed in the LMWHs studied, the doses used, and the inclusion of different cancers. Furthermore, because the primary question was addressing recurrent thrombosis and not survival, we wonder whether there was really accurate reporting of the causes of death in these trials. The CLOT trial also reported on the mortality of patients treated for 6 months, whereas the other studies treated patients for only 3 months.3 We do agree, however, with Ferretti et al that the antineoplastic effect of LMWHs should be studied further in randomized trials. There are a number of hypotheses concerning the anticancer effect of LMWH, including effects on angiogenesis, apoptosis, and inflammation.5,6 The mechanism proposed by Altundag is interesting, but very speculative. There is a need for more mechanistic studies with LMWH. Authors' Disclosures of Potential Conflicts of Interest Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C)
REFERENCES
1. Prandoni P, Lensing AWA, Piccioli A, et al: Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100:3484-3488, 2002
2. Hutten BA, Prins MH, Gent M, et al: Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: A retrospective analysis. J Clin Oncol 18:3078-3083, 2000
3. Lee AY, Levine MN, Baker RI, et al: Low molecular weight heparin versus a coumarin for prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:146-153, 2003
4. Lee AYY, Rickles FR, Julian JA, 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 23:2123-2129, 2005
5. Collen A, Smorenburg SM, Peters E, et al: Unfractionated and low molecular weight heparin affect fibrin structure and angiogenesis in vitro. Cancer Res 60:6196-6200, 2000 6. Kakkar AK, Levine MN: Thrombosis and cancer: Implications beyond Trousseau. J Thrombo Haemost 2:1261-1262, 2004[CrossRef]
Related Correspondence
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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$100,000 (N/R) Not Required
