Effect of Fraxiparine and heparin on experimental tumor metastasis in mice.

BACKGROUND Low molecular weight heparins (LMWH) have become increasingly important in anticoagulant therapy. Antitumor and antimetastatic activity of heparin and LMWH-s have also been reported. MATERIALS AND METHODS Fraxiparine, a new modified LMW-H, was tested for antimetastatic effect using 3LL-HH intravenous, B16 intra-foot pad and 3LL-HH intrasplenic models in C57 Bl/6 mice. The dose of Fraxiparine was 38, 57 and 172 IU/kg, respectively. Heparin (100 IU/kg) was used as a positive control. Both pre-treatment (starting 6 hours before tumor inoculation) and post-treatment (starting 24 hours after tumor inoculation), followed by daily injections, were applied in the intra-foot pad and intrasplenic models. In the intravenous model, only a single dose was administered one hour after tumor cell injection. RESULTS Fraxiparine at the dose of 57 IU/kg was significantly antimetastatic in the intravenous model. Continuous treatment, starting 6 hours before tumor inoculation, with 173 IU/kg Fraxiparine resulted in a strong inhibition of lung metastases in the intra-foot pad model, but was ineffective in the intrasplenic model. Heparin did not influence the metastasis number in any of the metastasis models. CONCLUSION These data may be of importance in the anticoagulant treatment of human cancer patients.