Clinical Studies with Anticoagulants to Improve Survival in Cancer Patients

Abstract

Cancer is linked with hypercoagulability and risk of thrombosis and this close association was recognized by Armand Trousseau in 1865. The relation between cancer and blood coagulation is reciprocal: cancer induces a hypercoagulable state and predisposes to thrombosis and activation of platelets, blood coagulation and fibrinolysis interfere with tumor cell biology, tumor growth, angiogenesis and metastatic process. In the present article, we analyze the clinical trials which assessed the influence of anticoagulant treatment on the survival of patients with cancer. The available data show that low-molecular-weight heparins (LMWHs) tend to be more effective and safer than vitamin K antagonists (VKA) in improving survival in patients with cancer. The beneficial effect of anticoagulation with either LMWHs or VKA is not universal for all patients with cancer. There are some histological types of cancers which, at early stages, appear to be more sensitive than others to the effect of anticoagulant treatment. The available clinical trials, although limited, are encouraging for the beneficial effect of anticoagulant treatment on the survival of cancer patients. More clinical trials are needed, targeting groups of patients homogenous regarding the type of cancer, the stage of the disease and life expectancy. The forthcoming clinical trials have to address some issues regarding the optimal dose, the timing and the duration of treatment with LMWH in relation to chemotherapy or other anticancer therapies.

The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

“…However, this bias, where present, would artificially enhance survival among warfarin users, but there was little evidence of any strong protective effects of warfarin in the present analysis. Finally, the study did not investigate low molecular weight heparins, which, despite short courses of treatment, may be well tolerated with fewer bleeding complications than warfarin and encouragingly also appear to improve cancer survival [2,41,42].…”

Deadly allies: the fatal interplay between platelets and metastasizing cancer cells

“…93,94 Because such activities were thought to be an exclusive result of the anticoagulatory capacity of heparin, clinical trials were conducted with the more easily manageable and orally available anticoagulant drug warfarin, a vitamin K antagonist, which, unfortunately, failed to show any clinical benefit for most types of cancer, except for small cell lung cancer. 95,96 Rather than merely blocking coagulation, heparins can inhibit the interaction of P-selectin with its natural ligands as heparins possess characteristics similar to natural P-selectin ligands. 75 Therefore, a single dose of unfractionated heparin can, at least in murine models of experimental metastasis, effectively attenuate metastasis, a phenomenon that is not dependent on the anticoagulatory qualities of heparin and that is abated in mice lacking P-seletin.…”

New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients

“…Several lines of evidence suggest that in some groups of cancer patients, the administration of LMWHs might improve cancer-related mortality 15. The interactions of NOACs with cancer cells have not yet been studied.…”