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 |
| . | 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.
Disclosures: No relevant conflicts of interest to declare.
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