title: The effect of therapeutic anticoagulation on overall survival in men receiving first-line docetaxel chemotherapy for metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Anticoagulants have been postulated to possess antitumor activity, although clinical data supporting this claim are conflicting. No definitive data exist on the clinical impact of anticoagulation therapy in patients with prostate cancer. The aim of this study was to investigate the association between therapeutic anticoagulant use and survival in men with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel chemotherapy.
  
  
  METHODS
  We retrospectively reviewed the records of 247 consecutive patients with mCRPC who received first-line docetaxel chemotherapy between 1998 and 2010 at a single institution. Among them, 29 patients (11.7 %) received therapeutic anticoagulation (low-molecular-weight heparin [LMWH] or warfarin) for the treatment of venous thromboembolism. Univariate and multivariable Cox proportional hazards regression models were used to investigate the effect of anticoagulant use on overall survival.
  
  
  RESULTS
  In univariate analysis, anticoagulant use was associated with improved survival (hazard ratio [HR], 0.61; P = .024). Median survival was 20.9 months in the anticoagulation group versus 17.1 months in the control group (P = .024). In multivariable analysis, anticoagulant use remained a significant predictor of survival after adjusting for other baseline prognostic factors (HR, 0.49; P = .023). When each anticoagulant was considered separately in the multivariable model, LMWH remained significantly prognostic for survival (HR, 0.48; P = .035), whereas warfarin use did not.
  
  
  CONCLUSIONS
  Anticoagulant use (LMWH in particular) is an independent predictor of improved survival in men with mCRPC receiving docetaxel. These data provide the impetus to further explore the antitumor properties of anticoagulants in patients with prostate cancer and warrant validation in prospective studies.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Park
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Pratz
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC.
authors.forename: Anteneh
authors.initials: A
authors.lastname: Tesfaye
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. Electronic address: eantona1@jhmi.edu.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Antonarakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D000077143:Docetaxel; D004357:Drug Synergism; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D043823:Taxoids; D000077143:Docetaxel; D014859:Warfarin
keywords: Anticoagulation; Docetaxel; Metastatic castration-resistant prostate cancer; Overall survival