title: Anticoagulant therapy of cancer patients: Will patient selection increase overall survival?
abstract: Already since the early 1800s, it has been recognised that malignancies may provoke thromboembolic complications, and indeed cancer patients are at increased risk of developing venous thrombosis. Interestingly, case control studies of deep-vein thrombosis suggested that low-molecular-weight heparin (LMWH) improved survival of cancer patients. This led to the hypothesis that cancer cells might 'take advantage' of a hypercoagulable state to more efficiently metastasise. Initial randomised placebo control trials showed that LMWH improve overall survival of cancer patients, especially in those patients with a relatively good prognosis. The failure of recent phase III trials, however, tempers enthusiasm for anticoagulant treatment in cancer patients despite an overwhelming body of literature showing beneficial effects of anticoagulants in preclinical models. Instead of discarding LMWH as potential (co)treatment modality in cancer patients, these disappointing recent trials should guide future preclinical research on anticoagulants in cancer biology. Most and for all, the underlying mechanisms by which coagulation drives tumour progression need to be elucidated. This could ultimately allow selection of cancer patients most likely to benefit from anticoagulant treatment and/or from targeted therapy downstream of coagulation factor signalling.
authors.affiliation: C. Arnold Spek, H2-157, Academic Medical Center, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands, Tel.: +31 20 5668750, E-mail: c.a.spek@amc.nl.
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Spek
authors.forename: Henri H
authors.initials: HH
authors.lastname: Versteeg
authors.forename: Keren S
authors.initials: KS
authors.lastname: Borensztajn
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D018579:Patient Selection; D018570:Risk Assessment; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants
keywords: Blood coagulation; heparin; low-molecular-weight; neoplasms; patient selection; proteinase-activated; receptors