This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.ABSTRACTHYPOTHESISTopotecan is a camptothecin analogue that interacts with DNA topoisomerase I, causing breakage in DNA strands during replication. Topotecan has antitumor activity against various pediatric solid tumors including neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, and medulloblastoma.
SPECIFIC AIMS Objectives:To estimate the response rate of two cycles of intravenous topotecan in children with recurrent Wilms tumor of favorable histology that is refractory to standard curative therapy.To describe the anti-tumor activity of topotecan in children with recurrent Wilms tumor of anaplastic histology.To assess the relation between CYP3A4/5 genotype and the phannocokinetics and pharmacodynamics of topetecan.To assess the relation between ABCG2 genotype and the pharmacokinetics and pharmacodynamics of topotecan.
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