Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts.
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.
Zucchetti
Massimo
M
Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, Italy. zucchetti@marionegri.it
Meco
Daniela
D
Di Francesco
Angela Maria
AM
Servidei
Tiziana
T
Patriarca
Valentina
V
Cusano
Gabriella
G
D'Incalci
Maurizio
M
Forestieri
Daniele
D
Pisano
Claudio
C
Riccardi
Riccardo
R
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
D000972:Antineoplastic Agents, Phytogenic; C433984:ST 1481; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077146:Irinotecan; C022616:thiazolyl blue; D002166:Camptothecin