title: 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.affiliation: Division of Internal and Cardiovascular Medicine and Stroke Unit, Department of Internal Medicine, University of Perugia, Perugia, Italy. agnellig@unipg.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Kakkar
authors.forename: William
authors.initials: W
authors.lastname: Fisher
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lassen
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.forename: Patrick
authors.initials: P
authors.lastname: Mouret
authors.forename: Umesh
authors.initials: U
authors.lastname: Chaudhari
authors.forename: Francesca
authors.initials: F
authors.lastname: Lawson
authors.forename: Alexander G G
authors.initials: AG
authors.lastname: Turpie
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005344:Fibrinopeptide A / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000453:epidemiology; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D005344:Fibrinopeptide A; C569346:semuloparin