title: Dalteparin low molecular weight heparin (LMWH) in ovarian cancer: a phase II randomized study.
abstract: OBJECTIVE
  Low molecular weight heparin reduces the risk of venous thromboembolism (VTE) and may have antineoplastic effects by interfering with angiogenesis and with tumor growth and metastasis. A multicentre phase II randomized trial was done to evaluate the antineoplastic potential of dalteparin in ovarian cancer (OC).
  
  
  METHODS
  Women with newly-diagnosed epithelial OC were randomized to receive standard chemotherapy (CT) and one of 3 doses of dalteparin (50 IU/kg, 100 IU/kg, or 150 IU/kg) subcutaneously once daily during the first 3 of 6 cycles of 3-weekly CT. Blood was drawn on day 1 of each cycle for CA125 and, in a substudy of randomized patients, for markers of coagulation activation and angiogenesis. The primary outcome was tumor response defined by ≥ 50% reduction in serum CA125 from baseline sustained for at least 28 days. Patients were followed until the end of CT.
  
  
  RESULTS
  The study was terminated early due to poor recruitment. Seventy-seven women were evaluable for the primary outcome. A 50% drop in CA125 at the end of cycle 3 was seen in 85% of the 50 IU/kg group, 92% of the 100 IU/kg group, and 85% of the 150 IU/kg group. There were no symptomatic VTE or major bleeding events while on dalteparin. Two patients experienced VTE several days after discontinuing study drug. Women on dalteparin had lower levels of D-dimer and thrombin-antithrombin, and higher levels of tissue factor pathway inhibitor, relative to baseline.
  
  
  CONCLUSIONS
  Dalteparin is safe and well tolerated in women receiving CT for newly-diagnosed epithelial OC. A dose-response effect was not identified. The lack of control group precluded any inference on the antineoplastic effect of dalteparin.
authors.affiliation: Ontario Clinical Oncology Group (OCOG), McMaster University, Hamilton, Canada. laurie.elit@jcc.hhsc.ca
authors.forename: Laurie M
authors.initials: LM
authors.lastname: Elit
authors.forename: Agnes Y
authors.initials: AY
authors.lastname: Lee
authors.forename: Sameer
authors.initials: S
authors.lastname: Parpia
authors.forename: Laura L
authors.initials: LL
authors.lastname: Swystun
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Liaw
authors.forename: Paul
authors.initials: P
authors.lastname: Hoskins
authors.forename: Denise H
authors.initials: DH
authors.lastname: Julian
authors.forename: Jim A
authors.initials: JA
authors.lastname: Julian
authors.forename: Mark N
authors.initials: MN
authors.lastname: Levine
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D017985:Dalteparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000097:blood / Q000098:blood supply / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D009944:Organoplatinum Compounds; D043823:Taxoids; C080625:taxane; D017985:Dalteparin