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 
    Endometrial cancer 
    Gastric or esophageal 4/2 3/1 
    Colorectal cancer 6/2 8/2 
    Prostatic cancer 
    Urothelial 
    Lung 
Death 
    Major bleeding 
    Minor bleeding 
    Allergic reaction 
    VTE 
Concomitant anti-neoplastic therapy 
    Chemotherapy 26 26 
    Radiotherapy 
    Combined 
        Hormonal 
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 
    Endometrial cancer 
    Gastric or esophageal 4/2 3/1 
    Colorectal cancer 6/2 8/2 
    Prostatic cancer 
    Urothelial 
    Lung 
Death 
    Major bleeding 
    Minor bleeding 
    Allergic reaction 
    VTE 
Concomitant anti-neoplastic therapy 
    Chemotherapy 26 26 
    Radiotherapy 
    Combined 
        Hormonal 

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.

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author