Evaluation of ABT-751 against childhood cancer models in vivo

Invest New Drugs. 2007 Aug;25(4):285-95. doi: 10.1007/s10637-007-9042-y. Epub 2007 Mar 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimitotic Agents / administration & dosage
  • Antimitotic Agents / therapeutic use*
  • Cell Line, Tumor
  • Child
  • Female
  • Humans
  • Mice
  • Mice, SCID
  • Neoplasms, Experimental / drug therapy*
  • Pediatrics
  • Sulfonamides / administration & dosage
  • Sulfonamides / therapeutic use*
  • Xenograft Model Antitumor Assays


  • ABT751
  • Antimitotic Agents
  • Sulfonamides