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.
© 2013 Wiley Periodicals, Inc.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Bone Neoplasms / drug therapy
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Bone Neoplasms / pathology
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Cell Proliferation / drug effects
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DNA Topoisomerases, Type II / chemistry*
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Drug Evaluation, Preclinical
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Female
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Humans
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Isoquinolines / pharmacokinetics
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Isoquinolines / pharmacology*
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / pathology
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Mice
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Mice, SCID
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Rhabdomyosarcoma / drug therapy*
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Rhabdomyosarcoma / pathology
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Sarcoma, Ewing / drug therapy*
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Sarcoma, Ewing / pathology
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Tissue Distribution
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Topoisomerase II Inhibitors / pharmacokinetics
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Topoisomerase II Inhibitors / pharmacology*
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Tumor Cells, Cultured
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Wilms Tumor / drug therapy*
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Wilms Tumor / pathology
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Xenograft Model Antitumor Assays
Substances
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Isoquinolines
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Topoisomerase II Inhibitors
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DNA Topoisomerases, Type II
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pixantrone