title: Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts.
abstract: OBJECTIVE
  This study compared the antitumor activity and the pharmacological profile of gimatecan given orally and irinotecan (CPT-11) on pediatric tumor xenografts.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The antitumor activity and the promising pharmacological profile indicate gimatecan as an excellent candidate for clinical treatment of pediatric tumors.
authors.affiliation: Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, Italy. zucchetti@marionegri.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Zucchetti
authors.forename: Daniela
authors.initials: D
authors.lastname: Meco
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Di Francesco
authors.forename: Tiziana
authors.initials: T
authors.lastname: Servidei
authors.forename: Valentina
authors.initials: V
authors.lastname: Patriarca
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cusano
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.forename: Daniele
authors.initials: D
authors.lastname: Forestieri
authors.forename: Claudio
authors.initials: C
authors.lastname: Pisano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D000077146:Irinotecan; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D013778:Tetrazolium Salts; D013844:Thiazoles; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C433984:ST 1481; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077146:Irinotecan; C022616:thiazolyl blue; D002166:Camptothecin