- J Pediatr Surg. 2001 Aug;36(8):1177-81
of Pediatric Surgery, and the Department of Pathology, College of
Physicians and Surgeons, Columbia University, New York, NY, USA.
Antibody to vascular endothelial growth factor (anti-VEGF) suppresses
tumor growth and metastasis in experimental Wilms tumor. However, tumor
growth accelerates if antibody is withdrawn. As recently shown,
low-dose, frequently administered topotecan, a topoisomerase-1
inhibitor, has anti-angiogenic activity. The authors hypothesized that
combined topotecan/anti-VEGF therapy would suppress tumor growth and
metastasis more durably than either agent alone.
were induced by intrarenal injection of human Wilms tumor cells in
athymic mice (n = 59). Mice were divided into control (n = 10),
anti-VEGF (n = 16), topotecan (n = 17), and topotecan plus anti-VEGF (n
= 16) groups. All control and half the treated mice were killed at week
6. Remaining ("rebound") mice were maintained without treatment until
week 8. Tumor vasculature was mapped by fluorescein angiography/PECAM
immunostaining. Endothelial apoptosis was assessed by TUNEL assay.
RESULTS: 6 weeks: Tumor weights were reduced significantly in treated
mice (P <.003 v control). Seven of ten control and 1 of 25 treated
mice displayed lung metastases (P <.003). Rebound tumors were
largest in topotecan-only, intermediate in antibody-treated, and
smallest in combination-treated mice. Immunostaining and angiography
results showed sparse vascularity in treated xenografts. Endothelial
apoptosis was observed only in treated tumors.
low-dose topotecan and anti-VEGF antibody therapy is antiangiogenic and
suppresses tumor growth and metastasis in experimental Wilms tumor more
durably than either agent alone.