Originally published as JCO Early Release 10.1200/JCO.2005.03.134 on February 7 2005

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klerk, C. P.W. Articles by Büller, H. R. Search for Related Content PubMed PubMed Citation Articles by Klerk, C. P.W. Articles by Büller, H. R. Related Articles Related Editorial Social Bookmarking                            What's this?

The Effect of Low Molecular Weight Heparin on Survival in Patients With Advanced Malignancy

From the Departments of Vascular Medicine, Medical Oncology, and Radiation Oncology, Academic Medical Center, University of Amsterdam; Department of Medical Oncology, Slotervaart Hospital, Amsterdam; Department of Clinical Epidemiology and Medical Technology Assessment, Academic Hospital Maastricht, University of Maastricht, the Netherlands; Servizio Malattie Tromboemboliche, IRCCS Policlinico San Matteo, Pavia; Department of Medical and Surgical Sciences, Clinica Medica II, University Hospital of Padua, Italy; Department of Oncology, Reinier de Graaf Group, Delft, the Netherlands

Address reprint requests to Clara P.W. Klerk, MD, Department of Vascular Medicine, Academic Medical Center F4-139, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; e-mail: c.p.klerk{at}amc.uva.nl

PURPOSE: Studies in cancer patients with venous thromboembolism suggested that low molecular weight heparin may prolong survival. In a double-blind study, we evaluated the effect of low molecular weight heparin on survival in patients with advanced malignancy without venous thromboembolism.

METHODS: Patients with metastasized or locally advanced solid tumors were randomly assigned to receive a 6-week course of subcutaneous nadroparin or placebo. The primary efficacy analysis was based on time from random assignment to death. The primary safety outcome was major bleeding.

RESULTS: In total, 148 patients were allocated to nadroparin and 154 patients were allocated to placebo. Mean follow-up was 1 year. In the intention-to-treat analysis the overall hazard ratio of mortality was 0.75 (95% CI, 0.59 to 0.96) with a median survival of 8.0 months in the nadroparin recipients versus 6.6 months in the placebo group. After adjustment for potential confounders, the treatment effect remained statistically significant. Major bleeding occurred in five (3%) of nadroparin-treated patients and in one (1%) of the placebo recipients (P = .12). In the a priori specified subgroup of patients with a life expectancy of 6 months or more at enrollment, the hazard ratio was 0.64 (95% CI, 0.45 to 0.90) with a median survival of 15.4 and 9.4 months, respectively. For patients with a shorter life expectancy, the hazard ratio was 0.88 (95% CI, 0.62 to 1.25).

CONCLUSION: A brief course of subcutaneous low molecular weight heparin favorably influences the survival in patients with advanced malignancy and deserves additional clinical evaluation.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Editorial

• Antithrombotic Therapy in Cancer
  Nicholas R. Lemoine
  JCO 2005 23: 2119-2120 [Full Text]

This article has been cited by other articles:

				A. A. Khorana Cancer and thrombosis: implications of published guidelines for clinical practice Ann. Onc., June 26, 2009; (2009) mdp068v1. [Abstract] [Full Text] [PDF]

				M. F. Barginear, M. Lesser, M. L. Akerman, M. Strakhan, I. Shapira, T. Bradley, and D. R. Budman Need for Inferior Vena Cava Filters in Cancer Patients: A Surrogate Marker for Poor Outcome Clinical and Applied Thrombosis/Hemostasis, June 1, 2009; 15(3): 263 - 269. [Abstract] [PDF]

				B. BABU and T. L. CARMAN Cancer and clots: All cases of venous thromboembolism are not treated the same Cleveland Clinic Journal of Medicine, February 1, 2009; 76(2): 129 - 135. [Abstract] [Full Text] [PDF]

				C. W. Francis and N. Kuderer Effects of Anticoagulants on Survival for Patients with Cancer ASCO Educational Book, January 1, 2009; 2009(1): 326 - 330. [Abstract] [Full Text] [PDF]

				N. H. Osborne, T. W. Wakefield, and P. K. Henke Venous Thromboembolism in Cancer Patients Undergoing Major Surgery Ann. Surg. Oncol., December 1, 2008; 15(12): 3567 - 3578. [Abstract] [Full Text] [PDF]

				C. Ay, R. Simanek, R. Vormittag, D. Dunkler, G. Alguel, S. Koder, G. Kornek, C. Marosi, O. Wagner, C. Zielinski, et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS) Blood, October 1, 2008; 112(7): 2703 - 2708. [Abstract] [Full Text] [PDF]

				D. E. Gerber, J. B. Segal, M. Y. Levy, J. Kane, R. J. Jones, and M. B. Streiff The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention Blood, August 1, 2008; 112(3): 504 - 510. [Abstract] [Full Text] [PDF]

				D. L. Ornstein, C. B. Bifulco, D. T. Braddock, and J. G. Howe Histopathologic and Molecular Aspects of CD56+ Natural Killer/ T-Cell Lymphoma of the Testis International Journal of Surgical Pathology, July 1, 2008; 16(3): 291 - 300. [Abstract] [PDF]

				C. Fotopoulou, A. duBois, A. N. Karavas, R. Trappe, B. Aminossadati, B. Schmalfeldt, J. Pfisterer, and J. Sehouli Incidence of Venous Thromboembolism in Patients With Ovarian Cancer Undergoing Platinum/Paclitaxel-Containing First-Line Chemotherapy: An Exploratory Analysis by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group J. Clin. Oncol., June 1, 2008; 26(16): 2683 - 2689. [Abstract] [Full Text] [PDF]

				W. H. Geerts, D. Bergqvist, G. F. Pineo, J. A. Heit, C. M. Samama, M. R. Lassen, and C. W. Colwell Prevention of Venous Thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 381S - 453S. [Abstract] [Full Text] [PDF]

				D. Nguyen, S.-J. Lee, E. Libby, and C. Verschraegen Rate of Thromboembolic Events in Mesothelioma Ann. Thorac. Surg., March 1, 2008; 85(3): 1032 - 1038. [Abstract] [Full Text] [PDF]

				J. E. Italiano Jr, J. L. Richardson, S. Patel-Hett, E. Battinelli, A. Zaslavsky, S. Short, S. Ryeom, J. Folkman, and G. L. Klement Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet {alpha} granules and differentially released Blood, February 1, 2008; 111(3): 1227 - 1233. [Abstract] [Full Text] [PDF]

				G. H. Lyman, A. A. Khorana, A. Falanga, D. Clarke-Pearson, C. Flowers, M. Jahanzeb, A. Kakkar, N. M. Kuderer, M. N. Levine, H. Liebman, et al. American Society of Clinical Oncology Guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer J. Clin. Oncol., December 1, 2007; 25(34): 5490 - 5505. [Abstract] [Full Text] [PDF]

				N. Hostettler, A. Naggi, G. Torri, R. Ishai-Michaeli, B. Casu, I. Vlodavsky, and L. Borsig P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins FASEB J, November 1, 2007; 21(13): 3562 - 3572. [Abstract] [Full Text] [PDF]

				A. A. Khorana The NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease: Strategies for Improving VTE Prophylaxis in Hospitalized Cancer Patients Oncologist, November 1, 2007; 12(11): 1361 - 1370. [Abstract] [Full Text] [PDF]

				J. Nishioka and S. Goodin Low-molecular-weight heparin in cancer-associated thrombosis: treatment, secondary prevention, and survival Journal of Oncology Pharmacy Practice, June 1, 2007; 13(2): 85 - 97. [Abstract] [PDF]

				R. De Caterina, S. Husted, L. Wallentin, G. Agnelli, F. Bachmann, C. Baigent, J. Jespersen, S. D. Kristensen, G. Montalescot, A. Siegbahn, et al. Anticoagulants in heart disease: current status and perspectives Eur. Heart J., April 10, 2007; (2007) ehl492v1. [Full Text] [PDF]

				R. Simanek, R. Vormittag, M. Hassler, K. Roessler, M. Schwarz, C. Zielinski, I. Pabinger, and C. Marosi Venous thromboembolism and survival in patients with high-grade glioma Neuro-oncol, April 1, 2007; 9(2): 89 - 95. [Abstract] [Full Text] [PDF]

				H. K. Chew, T. Wun, D. J. Harvey, H. Zhou, and R. H. White Incidence of Venous Thromboembolism and the Impact on Survival in Breast Cancer Patients J. Clin. Oncol., January 1, 2007; 25(1): 70 - 76. [Abstract] [Full Text] [PDF]

				G. W. Yip, M. Smollich, and M. Gotte Therapeutic value of glycosaminoglycans in cancer. Mol. Cancer Ther., September 1, 2006; 5(9): 2139 - 2148. [Abstract] [Full Text] [PDF]

				K. Altundag, O. Altundag, M. A. Atik, C. Boruban, M. B. Altundag, and S. Turen Recent Findings for Anti-Metastatic Potential of Heparin Clinical and Applied Thrombosis/Hemostasis, July 1, 2006; 12(3): 376 - 377. [PDF]

				K. Sideras, P. L. Schaefer, S. H. Okuno, J. A. Sloan, L. Kutteh, T. R. Fitch, S. R. Dakhil, R. Levitt, S. R. Alberts, R. F. Morton, et al. Low-Molecular-Weight Heparin in Patients With Advanced Cancer: A Phase 3 Clinical Trial Mayo Clin. Proc., June 1, 2006; 81(6): 758 - 767. [Abstract] [Full Text] [PDF]

				L. Y. Han, C. N. Landen Jr, A. A. Kamat, A. Lopez, D. P. Bender, P. Mueller, R. Schmandt, D. M. Gershenson, and A. K. Sood Preoperative Serum Tissue Factor Levels Are an Independent Prognostic Factor in Patients With Ovarian Carcinoma J. Clin. Oncol., February 10, 2006; 24(5): 755 - 761. [Abstract] [Full Text] [PDF]

				A. Y. Y. Lee Thrombosis and Cancer: The Role of Screening for Occult Cancer and Recognizing the Underlying Biological Mechanisms Hematology, January 1, 2006; 2006(1): 438 - 443. [Abstract] [Full Text] [PDF]

				P. Prandoni How I treat venous thromboembolism in patients with cancer Blood, December 15, 2005; 106(13): 4027 - 4033. [Abstract] [Full Text] [PDF]

				S. Goodin Selecting an anticoagulant for recurrent venous thromboembolism in cancer Am. J. Health Syst. Pharm., November 15, 2005; 62(22_Supplement_5): S10 - S13. [Abstract] [Full Text] [PDF]

				Low-Molecular-Weight Heparin to Treat Cancer? Journal Watch (General), April 26, 2005; 2005(426): 3 - 3. [Full Text]