Figure 2.

Induction of solid tumor regression by nontoxic, antiangiogenic combination therapy with low-dose vinblastine and anti–flk-1 antibody (DC101). Top panel: Established xenografts of human neuroblastoma (SK-N-MC) were treated by a putative antivascular regimen of low-dose vinblastine (induction: 0.75 mg/m² bolus intraperitoneally; 1 mg/m² per day continuous subcutaneous infusion for 3 weeks; maintenance: 1.5 mg/m² every 3 days) alone or in combination with an anti–VEGF-R2 antibody (DC101; 800 μg every 3 days). There is an appreciable tumor growth inhibition by each of the single agents, which is comparable, at least initially, with that of the combination treatment group. The benefit of the combination treatment is most evident after prolonged treatment, when lasting and complete tumor regression is observed. The data are a compilation of 2 independent experiments, with the initial experiment lasting 34 days and the second still ongoing (> 210 days). In both sets, 20 mice were randomized into 4 groups. Bottom panel: Lack of toxicity-dependent weight loss in mice bearing SK-N-MC tumor xenografts treated with “antivascular” vinblastine regimen alone or in combination with and anti–VEGF-R2 (DC101) antibody. There are no significant differences in weight between the groups, except for a transient (14–18 days long) episode of weight loss associated with diarrhea in the combination treatment group. The episode resolved without interruption of therapy. Average body weights (g) ± SD are plotted (n = 3–10 mice). ip, intraperitoneally.