Antitumor effect of a neutralizing antibody to vascular endothelial growthfactor on liver metastasis of endocrine neoplasm

Distant metastasis of gastrointestinal endocrine neoplasm is resistant to c urrently available treatments. Because hematogenic metastasis is dominant, anti-angiogenic drugs are expected to be a novel therapy for this neoplasm, In the present study, the therapeutic effect of vascular endothelial growt h factor neutralizing antibody (VEGFAb) on liver metastasis of an endocrine neoplasm was investigated experimentally. Cecal transplantation into nude mice of small pieces of EN-1, a xenotransplanted human intestinal endocrine neoplasm, resulted in liver metastasis. A treated group (n=19) received 10 0 mu g/mouse of VEGFAb intraperitoneally on alternate days from day 10 afte r tumor transplantation, and the control group (n=19) received saline. Five of the 19 control mice died of tumor progression, of which 2 could not be evaluated. The cecal tumor weighed 6316+/-2333 mg (n=17) in the control gro up and 1209+/-837 mg (n=19) in the treated group (P<0.01) 6 weeks after tra nsplantation. Liver metastasis developed in 16 of 17 control mice and in 2 of 19 treated mice (P<0.01). The VEGF level of the whole cecal tumor in the control group was significantly higher than that in the treated group (305 .1+/-174.1 vs. 54.7+/-41.2 mg; P<0.001). VEGFAb did not cause any body weig ht loss (28.52+/-1.63 in the control vs. 28.44+/-1.71 g in the treated grou p). These results indicate that VEGFAb may be a novel therapeutic agent for endocrine neoplasm with distant metastasis.