The suppression of postoperative liver metastasis caused by the continuous intraportal infusion of angiogenesis inhibitor FR-118487 in a rabbit colon cancer model.

The inhibitory effect of FR-118487, a potent angiogenesis inhibitor, on neovascularization induced by the VX2 tumor was confirmed in a rabbit corneal assay. The antimetastatic effect of FR-118487 was also investigated in 21 rabbits. Spontaneous liver metastases were induced by VX2 tumor cell implantation into the ascending colonic wall. FR-118487 was then infused continuously into the portal vein for 7 days after resection of the primary lesion at a dose of 1 mg/kg/day (FR-1 group) or 3 mg/kg/day (FR-3 group). The incidence of liver metastases was 71.4%, occurring in 5 of 7 rabbits, in each of the FR-1 and FR-3 groups, compared with 100%, being all of 7 rabbits, in the control group. The number of metastatic foci tended to be less in the FR-1 (31.0 +/- 36.0) and FR-3 (24.6 +/- 45.1) groups than in the control group (83.7 +/- 73.9) and the weight of metastatic foci was significantly less in the FR-1 (1.4 +/- 1.8 g) and FR-3 (1.3 +/- 2.0 g) groups than in the control group (6.5 +/- 4.9 g) (P < 0.05). However, leakage of the colonic anastomosis and body weight loss were limited to the FR-3 group. These results suggest that the continuous intraportal infusion of FR-118487 at 1 mg/kg/day suppressed liver metastases by inhibiting angiogenesis, without producing any adverse effects.