Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program

Pediatr Blood Cancer. 2014 May;61(5):922-4. doi: 10.1002/pbc.24800. Epub 2013 Oct 26.

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.

Keywords: developmental therapeutics; preclinical testing; topoisomerase 2 inhibitor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / pathology
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type II / chemistry*
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Isoquinolines / pharmacokinetics
  • Isoquinolines / pharmacology*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / pathology
  • Mice
  • Mice, SCID
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / pathology
  • Sarcoma, Ewing / drug therapy*
  • Sarcoma, Ewing / pathology
  • Tissue Distribution
  • Topoisomerase II Inhibitors / pharmacokinetics
  • Topoisomerase II Inhibitors / pharmacology*
  • Tumor Cells, Cultured
  • Wilms Tumor / drug therapy*
  • Wilms Tumor / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Isoquinolines
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II
  • pixantrone