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01-09-2010 | Original Article

Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts

Authors: Massimo Zucchetti, Daniela Meco, Angela Maria Di Francesco, Tiziana Servidei, Valentina Patriarca, Gabriella Cusano, Maurizio D’Incalci, Daniele Forestieri, Claudio Pisano, Riccardo Riccardi

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2010

Abstract

Purpose

This study compared the antitumor activity and the pharmacological profile of gimatecan given orally and irinotecan (CPT-11) on pediatric tumor xenografts.

Experimental design

Gimatecan was tested in two neuroblastoma cell lines (SK-N-DZ and SK-N-(BE)2c) and on TE-671 rhabdomyosarcoma cells using two different schedules. We characterized its pharmacokinetic profile in nude mice bearing human SK-N-DZ and TE-671 cell lines.

Results

Gimatecan appears to have high plasma disposition. The drug was present in plasma almost completely as the intact lactone form and showed substantial activity in all tumor models. Prolonged daily treatment with low doses of gimatecan produced significant tumor regression in all tumor xenografts.

Conclusion

The antitumor activity and the promising pharmacological profile indicate gimatecan as an excellent candidate for clinical treatment of pediatric tumors.

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Title: Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts
Authors: Massimo Zucchetti
Daniela Meco
Angela Maria Di Francesco
Tiziana Servidei
Valentina Patriarca
Gabriella Cusano
Maurizio D’Incalci
Daniele Forestieri
Claudio Pisano
Riccardo Riccardi
Publication date: 01-09-2010
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-1201-8

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Abstract

Purpose

Experimental design

Results

Conclusion

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