title: Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: A randomized trial.
abstract: BACKGROUND
  Ambulatory cancer patients at high-risk for venous thromboembolism (VTE) can be identified using a validated risk score (Khorana score). We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in high-risk patients in a multicenter randomized study.
  
  
  METHODS
  Cancer patients with Khorana score≥3 starting a new systemic regimen were screened for VTE and if negative randomized to dalteparin 5000units daily or observation for 12weeks. Subjects were screened with lower extremity ultrasounds every 4weeks on study and with chest CT at 12weeks. The primary efficacy endpoint was all VTE over 12weeks and primary safety endpoint was clinically relevant bleeding events over 13weeks. The study was terminated early due to low accrual.
  
  
  RESULTS
  Of 117 enrolled patients, 10 (8.5%) had VTE on baseline screening and were not randomized. Of 98 randomized patients, VTE occurred in 12% (N=6/50) of patients on dalteparin and 21% (N=10/48) on observation (hazard ratio, HR 0.69, 95% CI 0.23-1.89). Major bleeding was similar (N=1) in each arm but clinically relevant bleeding was higher in dalteparin arm (N=7 versus 1 on observation) (HR=7.0, 95% CI 1.2-131.6). There was no difference in overall survival.
  
  
  CONCLUSIONS
  Thromboprophylaxis is associated with a non-significantly reduced risk of VTE and significantly increased risk of clinically relevant bleeding in this underpowered study. The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during treatment. Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer.
  
  
  BACKGROUND
  clinicaltrials.gov identifier: NCT00876915.
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA. Electronic address: Khorana@ccf.org.
authors.forename: Alok A
authors.initials: AA
authors.lastname: Khorana
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Francis
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Kuderer
authors.affiliation: University of Ottawa, Ottawa, ON, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Carrier
authors.affiliation: Thrombosis and Hemostasis Center, Division of Hematology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.affiliation: University of California, Sacramento, CA, USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Wun
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Rubens
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Hobbs
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Renuka
authors.initials: R
authors.lastname: Iyer
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Derick
authors.initials: D
authors.lastname: Peterson
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baran
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kaproth-Joslin
authors.affiliation: Division of Medical Oncology/Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Lyman
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D017985:Dalteparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology* / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D017985:Dalteparin