Abstract
The use of heparin for venous thromboembolism, upper extremity deep vein thrombosis (DVT), septic thrombophlebitis, loss of central venous device access in patients with cancer is a standard practice; a new clinical evidence suggest that low molecular weight heparin (LMWHs) may prolong survival in patients with cancer and may have anti-neoplastic effects and anti-metastatic activity.
We evaluated 74 patients with cancer (38 patients were allocated to enoxaparin 6000UI subcutaneously once a day, and 36 patients were allocated to placebo), the mean duration of follow-up was 12 months, platelet count were performed before the treatment, and once a month; in the event of thrombocytopenia < 50.000/ml or abnormal bleeding the treatment was stopped. The primary end points were overall survival, and metastasis progression.
TAB:A
Enoxaparin (n.38) Placebo (n.36) Age-years (range) 46–68 48–66 Sex (male/female) 20/18 20/16 Metastasis disease a) before 10 12 b) end-therapy 12 18 Type of cancer Breast cancer 8 8 Endometrial cancer 6 5 Gastric or esophageal 4/2 3/1 Colorectal cancer 6/2 8/2 Prostatic cancer 6 7 Urothelial 2 1 Lung 2 1 Death 3 8 Major bleeding 1 0 Minor bleeding 4 4 Allergic reaction 0 0 VTE 6 0 Concomitant anti-neoplastic therapy Chemotherapy 26 26 Radiotherapy 2 1 Combined 4 3 Hormonal 6 6
These data show that LMWHs reduce or attenuate metastasis at 12 month by 11.4%, and death by 8.8%, with a significant increase of median survival.
Heparin have show to have direct antigrowth, antiangiogenesis, and antimetastatic effects, LMWHs minimize angiogenesis with the inhibition of VEGF and b-FGF, inhibit the adhesion of cancer cells to endothelium and the interaction mediated by tumor cells surface mucins and selectin, and they interfere with cancer biology; we can speculate that the binding of tumor growth to heparin have a crucial role in the modulation of activity of the high affinity receptors, it promotes receptors dimerization and activation, inhibits P and L-selectins and chemokine action (IL-8, Mip-1), blocks MMP, serin-protease and heparanase, decreases over-expression of TF and PAF, induces and increases apoptosis.
Thromboprophylaxis with low-molecular-weight heparin in medical patients with cancer
