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More Evidence that Low Molecular Weight Heparin Improves Mortality in Cancer Patients
Jodi L. Grabinski, Pharm.D., BCOP*
For more than 10 years the post-hoc analyses of DVT treatment studies have suggested the low molecular weight heparins (LMWH) may reduce cancer deaths substantially. Two recent studies - one done in cancer patients without thrombosis - provide new evidence that LMWHs may provide an impressive survival benefit, especially in those patients with less advanced disease.
The first study conducted by Lee and colleagues, was a post hoc analysis of the Comparison of Low Molecular Weight Heparin Versus Oral Anticoagulant Therapy for Long Term Anticoagulation in Cancer Patients with Venous Thromboembolism (CLOT) Trial. This study evaluated the safety and efficacy of dalteparin for the prevention of recurrent venous thromboembolism in 602 patients with cancer receiving 6 months of anticoagulation therapy. Twelve month survival data between the group receiving dalteparin (174 of 296 patients died) and those in the oral anticoagulant group (182 of 306 died) was not statistically significant (p=0.62). However, in a subgroup of patients without known metastases the Kaplan-Meier estimate of the probability of death at 12 months was 20% in the dalteparin group compared with 36% in the oral anticoagulant group (HR=0.50, 95% CI 0.27-0.95, p=0.03). The 50% risk reduction remained significant even after adjustment for other prognostic factors indicating that patients with less advanced disease derive a greater benefit in overall survival on LMWH.
The second study by Klerk and colleagues, was a double-blind, placebo-controlled study to evaluate the influence of LMWH (nadroparin) on survival in patients with advanced malignant disease with no venous thromboembolism. A total of 302 patients were enrolled into the study, 148 in the nadroparin group and 154 in the placebo group. Patients received a 6 week course of therapy. The median survival was 8 months in the treatment group compared with 6.6 months for the placebo group in the intention-to-treat population (HR 0.75, 95% CI 0.59-0.96, p=0.021). This significant finding remained even when adjusting for life expectancy, performance status, concomitant treatment and histology. This study also identified that patients with an estimated life expectancy of 6 months or more on nadroparin had a greater survival benefit (HR 0.64, 95% CI 0.45-0.9, p=0.10) than those with a life expectancy of less than 6 months (HR 0.88, 95% CI 0.62-1.25). It is also interesting to note that such a short course of therapy influenced survival for months to years after treatment.
These two studies provide further evidence that the use of LMWHs in patients with cancer not only provides an antithrombotic benefit but also may improve patient survival. Although the exact mechanism is unknown, the impact of LMWHs on tumor biology may exert an antiangiogenic effect on the tumor thereby influencing response. Future research is needed to elucidate the exact mechanism of LMWHs in cancer and to optimize their role in therapy.
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 Onc. 2005;23(10):2123-9.
Klerk CPW, Smorenburg SM, Otten H-M, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Onc. 2005;23(10):2130-5.
*Dr. Grabinski, who is a guest editor, is Pharmacogenomics Fellow in the Division of Pharmacotherapy at the University of Texas Health Science Center at San Antonio. Dr. Grabinski has previously served as a guest editor for ClotCare. Her other posting, Screening for Occult Cancer in Patients with Venous Thromboembolism, is available at http://www.clotcare.com/clotcare/occultcancer.aspx.
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