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: Raushan T Kurmasheva, C Patrick Reynolds, Min H Kang, Cecilia Allievi, Peter J Houghton, Malcolm A Smith
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 61 Issue 5 Pg. 922-4 (May 2014) ISSN: 1545-5017 [Electronic] United States
• PMID: 24166988 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

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

Topics

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