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Evaluation of ABT-751 against childhood cancer models in vivo
- Source :
- Investigational new drugs. 25(4)
- Publication Year :
- 2006
-
Abstract
- 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.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.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 (EFS2.0) in eight models (33%) in addition to those with objective responses.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.
- Subjects :
- Childhood cancer
Mice, SCID
Pharmacology
Antimitotic Agents
Pediatrics
Mice
In vivo
Colchicine binding
Cell Line, Tumor
Medicine
Animals
Humans
Pharmacology (medical)
Child
Sulfonamides
biology
business.industry
Pediatric Tumor
Phase i trials
Neoplasms, Experimental
Xenograft Model Antitumor Assays
Tubulin
Oncology
Cell culture
biology.protein
Antimitotic Agent
Female
business
Subjects
Details
- ISSN :
- 01676997
- Volume :
- 25
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Investigational new drugs
- Accession number :
- edsair.doi.dedup.....72fd6fb078426de04dfa2220887cbe30