Antiangiogenesis treatment combined with chemotherapy produces chondrosarcoma necrosis

A combination therapy protocol using a marine chemotherapeutic and an antiangiogenic molecule was tested in a mouse tumor xenograft model for the ability to curtail the growth of a human chondrosarcoma (CHSA). Ecteinascidin-743 (ET-743), a marine-derived chemotherapeutic, was effective at slowing the growth of a primary CHSA. Plasminogen-related protein B, which antagonizes various endothelial cell activities, also elicited a significant inhibition of neoplastic growth, albeit with reduced effectiveness. The combination of the two agents resulted in only a modest further repression of tumor growth over that associated with ET-743 treatment alone, as measured by tumor volume (82% versus 76% inhibition, respectively). However, analysis of the extent of tumor necrosis and vascularization of the tumor revealed that the coadministration of the two compounds was clearly more effective, eliciting a 2.5-fold increase in tumor necrosis relative to single-agent treatment. The combination therapy also was most effective at antagonizing tumor-associated microvessel formation, as assessed by CD31 immunostaining, suggesting that combination therapy may hold promise for treating CHSA. Tumor necrosis produced by combination therapy of ET-743 and recombinant plasminogen-related protein B was also significantly greater than that produced by conventional doxorubicin treatment, further corroborating the efficacy of combination therapy.