Novel use of an established agent: Topotecan is anti-angiogenic in experimental Wilms tumor

Background/Purpose:Antiangiogenic agents offer anew approach to the treatme nt of aggressive neoplasms, yet very few agents are available for current u se. The authors have shown previously the efficacy of antiangiogenic therap y in experimental Wilms tumor, using an investigative antibody. They hypoth esized that topotecan, administered in a regimen targeting endothelial cell s, would suppress tumor growth and angiogenesis in experimental Wilms tumor . Methods: Experimental tumors were induced in the left kidneys of athymic mi ce by injection of cultured Wilms tumor cells. Topotecan (0.36, 0.6, 1.0, 2 .0, and 3.0 mg/kg) or vehicle was injected intraperitoneally in 2 cycles ov er a 6-week period. Fluorescein angiograms and platelet endothelial cell ad hesion molecule-1 staining of primary tumors were performed to ascertain va scular architecture. Endothelial apoptosis was assessed by TdT-mediated dUT P nick end labeling assay. Results: Tumor weights were reduced significantly in treated versus control animals, even in the lowest-dose group. Endothelial cell staining and angi ography results showed relatively sparse vascularity in treated xenografts. Endothelial apoptosis was observed in treated but not control tumors. Conclusions: Topotecan, delivered in an "antiangiogenic" regimen, even at v ery low doses, significantly Inhibited growth of experimental Wilms tumors. No adverse effects were noted at low doses. Thus, the established chemothe rapy agent topotecan may be useful in a novel role: as antiangiogenic thera py. Copyright (C) 2001 by W.B. Saunders Company.