Evaluation of ABT-751 against childhood cancer models in vivo

Christopher L. Morton, Edward G. Favours, Kimberly S. Mercer, Claire R. Boltz, Jeri Carol Crumpton, Chandra Tucker, Catherine A. Billups, Peter J. Houghton

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Objective: ABT-751 is a novel antimitotic agent that binds tubulin at the colchicine binding site. ABT-751 is undergoing Phase I trials in children, but has not been evaluated against a range of pediatric tumor models in vivo. Materials and methods: ABT-751 was evaluated against 27 subcutaneously implanted xenograft models of childhood cancer including neuroblastoma [4], osteosarcoma [4], Ewing sarcoma [2] rhabdomyosarcoma [8], medulloblastoma [1] and eight kidney cancer lines (six Wilms tumors, two rhabdoid). ABT-751 was administered at 100 mg/kg P.O. on a schedule of 5 days on, 5 days off, 5 days on, repeating the cycle at 21 days. Tumor diameters were measured at 7 day intervals for a period of 12 weeks. Three measures of antitumor activity were used: (1) clinical response criteria [e.g., partial response (PR), complete response (CR), etc.]; (2) treated to control (T/C) tumor volume at day 21; and (3) a time to event measure based on the median event free survival (EFS) of treated and control lines. Results: ABT-751 induced regression in 4 of 25 models (16%) including models of neuroblastoma that are refractory to vincristine and paclitaxel. Other regressions occurred in rhabdomyosarcoma and Wilms tumor models. ABT-751 significantly increased event free survival (EFS>2.0) in eight models (33%) in addition to those with objective responses. Conclusions: ABT-751 demonstrated intermediate activity against this tumor panel. Neuroblastoma models appear somewhat more sensitive to this agent, with objective regressions also in rhabdomyosarcoma and Wilms tumor. ABT-751 was also active in several tumor lines intrinsically refractory to vincristine or paclitaxel.

Original languageEnglish (US)
Pages (from-to)285-295
Number of pages11
JournalInvestigational New Drugs
Volume25
Issue number4
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

Keywords

  • ABT-751
  • Pediatric preclinical testing
  • Xenogarft

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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  • Cite this

    Morton, C. L., Favours, E. G., Mercer, K. S., Boltz, C. R., Crumpton, J. C., Tucker, C., Billups, C. A., & Houghton, P. J. (2007). Evaluation of ABT-751 against childhood cancer models in vivo. Investigational New Drugs, 25(4), 285-295. https://doi.org/10.1007/s10637-007-9042-y