title: Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program.
abstract: Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0 nM to 30.0 μM) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5 mg/kg) administered intravenously using an every 4 day × 3 schedule. In vitro pixantrone showed a median relative IC50 value of 54 nM (range <3 nM to 1.03 μM). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels relevant to human drug exposure. A complete response was observed for one Wilms tumor xenograft.
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Raushan T
authors.initials: RT
authors.lastname: Kurmasheva
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Min H
authors.initials: MH
authors.lastname: Kang
authors.forename: Cecilia
authors.initials: C
authors.lastname: Allievi
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000473:pathology; D014018:Tissue Distribution; D059005:Topoisomerase II Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II; C086548:pixantrone
keywords: developmental therapeutics; preclinical testing; topoisomerase 2 inhibitor