Inhibition of tumor growth in a human neuroblastoma xenograft model with TNP-470.
Background and Procedure High-risk neuroblastoma disease features are correlated with tumor vascularity, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. We therefore examined the efficacy of TNP-470 (TAP Pharmaceuticals, Deerfield, IL) in human neuroblastoma xenograft models.


RESULTS
Tumor growth rate was markedly inhibited in mice receiving TNP-470 administered alone with a treatment to control ratio (T/C) at day 21 = 0.4 (P <.001). TNP-470 also significantly inhibited tumorigenicity when administered shortly after xenograft inoculation (T/C at day 30 = 0.1, P <.001) and when administered following cyclophosphamide (T/C at day 35 = 0.1, P <.001).


CONCLUSIONS
These data show that TNP-470 is a potent inhibitor of human neuroblastoma growth both alone and when given with conventional chemotherapy, suggesting that it may be a useful adjunctive therapy for high-risk neuroblastoma patients.
Shusterman
S
S
Division of Oncology, The Children's Hospital of Philadelphia, and Department of Pediatrics, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA. shusterman@email.chop.edu
Grupp
S A
SA
Maris
J M
JM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002648:Child; D003510:Cyclohexanes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018365:Neoplasm, Residual; D009447:Neuroblastoma / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol