Novel use of an established agent: Topotecan is anti-angiogenic in experimental Wilms tumor.
OBJECTIVE
Antiangiogenic agents offer a new approach to the treatment of aggressive neoplasms, yet very few agents are available for current use. The authors have shown previously the efficacy of antiangiogenic therapy in experimental Wilms tumor, using an investigative antibody. They hypothesized that topotecan, administered in a regimen targeting endothelial cells, would suppress tumor growth and angiogenesis in experimental Wilms tumor.


METHODS
Experimental tumors were induced in the left kidneys of athymic mice 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 over a 6-week period. Fluorescein angiograms and platelet endothelial cell adhesion molecule-1 staining of primary tumors were performed to ascertain vascular architecture. Endothelial apoptosis was assessed by TdT-mediated dUTP 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 angiography 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 very low doses, significantly inhibited growth of experimental Wilms tumors. No adverse effects were noted at low doses. Thus, the established chemotherapy agent topotecan may be useful in a novel role: as antiangiogenic therapy. J Pediatr Surg 36:1781-1784.
Soffer
S Z
SZ
Divisions of Pediatric Surgery and Pediatric Oncology and the Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Kim
E
E
Moore
J T
JT
Huang
J
J
Yokoi
A
A
Manley
C
C
O'Toole
K
K
Middlesworth
W
W
Stolar
C
C
Yamashiro
D
D
Kandel
J
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D019772:Topotecan / Q000494:pharmacology / Q000627:therapeutic use*; D009396:Wilms Tumor / Q000188:drug therapy* / Q000473:pathology
D020533:Angiogenesis Inhibitors; D019772:Topotecan