title: Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation.
abstract: BACKGROUND
  Basic research and clinical studies have generated the hypothesis that anticoagulation may improve survival in patients with cancer through an antitumour effect in addition to the antithrombotic effect.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of heparin (including unfractionated heparin (UFH) and low molecular weight heparin (LMWH)) and fondaparinux to improve survival of patients with cancer.
  
  
  METHODS
  A comprehensive search for studies of anticoagulation in cancer patients including (1) A January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI the Web of Science; (2) Hand search of the American Society of Clinical Oncology and of the American Society of Hematology; (3) Checking of references of included studies; and (4) Use of "related article" feature in PubMed.
  
  
  METHODS
  We included randomized controlled trials (RCTs) in cancer patients without clinical evidence of venous thromboembolism comparing UFH, LMWH or fondaparinux to no intervention or placebo and RCTs comparing two of the three agents of interest.
  
  
  METHODS
  Using a standardized form we extracted in duplicate data on methodological quality, participants, interventions and outcomes of interest including all cause mortality, venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding.
  
  
  RESULTS
  Of 3986 identified citations five RCTs fulfilled the inclusion criteria. In all included RCTs the intervention consisted of heparin ( either UFH or LMWH). The overall methodological quality of the included studies was acceptable. Overall, heparin therapy was associated with a statistically and clinically significant survival benefit (hazard ratio (HR) = 0.77; 95% CI: 0.65 to 0.91). In subgroup analyses, patients with limited small cell lung cancer experienced a clear survival benefit (HR = 0.56; 95% CI: 0.38 to 0.83). The survival benefit was not statistically significant for either patients with extensive small cell lung cancer (HR = 0.80; 95% CI: 0.60 to 1.06) or patients with advanced cancer (HR = 0.84; 95%: 0.68 to 1.03). The increased risk of bleeding with heparin was not statistically significant (RR = 1.78; 95% CI: 0.73 to 4.38).
  
  
  CONCLUSIONS
  Heparin has a survival benefit in cancer patients in general, and in patients with limited small cell lung cancer in particular. Heparin might be particularly beneficial in cancer patients with limited cancer or a longer life expectancy. Future research should investigate the survival benefit of different types of anticoagulants (in different dosing, schedules and duration of therapy) in patients with different types and stages of cancers.
authors.affiliation: State University of New York at Buffalo, Medicine, ECMC, CC-142, 462 Girder Street, Buffalo, New York, 14215, USA. elieakl@buffalo.edu
authors.forename: E A
authors.initials: EA
authors.lastname: Akl
authors.forename: F F
authors.initials: FF
authors.lastname: van Doormaal
authors.forename: M
authors.initials: M
authors.lastname: Barba
authors.forename: G
authors.initials: G
authors.lastname: Kamath
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Kuipers
authors.forename: S
authors.initials: S
authors.lastname: Middeldorp
authors.forename: V
authors.initials: V
authors.lastname: Yosuico
authors.forename: H O
authors.initials: HO
authors.lastname: Dickinson
authors.forename: H J
authors.initials: HJ
authors.lastname: Schünemann
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000401:mortality; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality; D009369:Neoplasms / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin; D006493:Heparin