Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer

N Engl J Med. 2012 Feb 16;366(7):601-9. doi: 10.1056/NEJMoa1108898.

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.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00694382