Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer.

Abstract

BACKGROUND:

Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism. Limited data support the clinical benefit of antithrombotic prophylaxis.

METHODS:

In this double-blind, multicenter trial, we evaluated the efficacy and safety of the ultra-low-molecular-weight heparin semuloparin for prevention of venous thromboembolism in patients receiving chemotherapy for cancer. Patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy were randomly assigned to receive subcutaneous semuloparin, 20 mg once daily, or placebo until there was a change of chemotherapy regimen. The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism, and death related to venous thromboembolism. Clinically relevant bleeding (major and nonmajor) was the main safety outcome.

RESULTS:

The median treatment duration was 3.5 months. Venous thromboembolism occurred in 20 of 1608 patients (1.2%) receiving semuloparin, as compared with 55 of 1604 (3.4%) receiving placebo (hazard ratio, 0.36; 95% confidence interval [CI], 0.21 to 0.60; P<0.001), with consistent efficacy among subgroups defined according to the origin and stage of cancer and the baseline risk of venous thromboembolism. The incidence of clinically relevant bleeding was 2.8% and 2.0% in the semuloparin and placebo groups, respectively (hazard ratio, 1.40; 95% CI, 0.89 to 2.21). Major bleeding occurred in 19 of 1589 patients (1.2%) receiving semuloparin and 18 of 1583 (1.1%) receiving placebo (hazard ratio, 1.05; 95% CI, 0.55 to 1.99). Incidences of all other adverse events were similar in the two study groups.

CONCLUSIONS:

Semuloparin reduces the incidence of thromboembolic events in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. (Funded by Sanofi; ClinicalTrials.gov number, NCT00694382.).

• Authors: Giancarlo Agnelli, Daniel J George, Ajay K Kakkar, William Fisher, Michael R Lassen, Patrick Mismetti, Patrick Mouret, Umesh Chaudhari, Francesca Lawson, Alexander G G Turpie, SAVE-ONCO Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 366 Issue 7 Pg. 601-9 (Feb 16 2012) ISSN: 1533-4406 [Electronic] United States
• PMID: 22335737 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Fibrinolytic Agents
• Heparin, Low-Molecular-Weight
• Fibrinopeptide A
• semuloparin

Topics

• Adult
• Antineoplastic Agents (adverse effects, therapeutic use)
• Double-Blind Method
• Fibrinolytic Agents (adverse effects, therapeutic use)
• Fibrinopeptide A (adverse effects, therapeutic use)
• Hemorrhage (epidemiology)
• Heparin, Low-Molecular-Weight (adverse effects, therapeutic use)
• Humans
• Incidence
• Kaplan-Meier Estimate
• Neoplasms (complications, drug therapy)
• Risk Factors
• Venous Thromboembolism (epidemiology, etiology, prevention & control)