Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts
2010
Zucchetti, Massimo | Meco, Daniela | Di Francesco, Angela Maria | Servidei, Tiziana | Patriarca, Valentina | Cusano, Gabriella | D'Incalci, Maurizio | Forestieri, Daniele | Pisano, Claudio | Riccardi, Riccardo
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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