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

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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.

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