title: Multicentre phase II and pharmacokinetic study of RFS2000 (9-nitro-camptothecin) administered orally 5 days a week in patients with glioblastoma multiforme.
abstract: A phase II trial was instigated to investigate the antitumour activity, the safety and the pharmacokinetic parameters of RFS2000, a recently identified oral topoisomerase I inhibitor, given once daily (1.5 mg/m(2)/day) as first-line chemotherapy treatment for patients with advanced glioblastoma multiforme (GBM). Between 9 March and 15 September 2000, 17 patients were entered onto the trial. 15 patients were considered eligible. A total of 49 cycles (range 1-8) were administered. Grade 3-4 toxicity was observed in 5 patients. Neutropenia and thrombocytopenia were common toxicities. Pharmacokinetic analysis showed that 9-nitro camptothecin (9-NC) could be detected in the plasma and is progressively converted into 9-amino-camptothecin (9-AC). The response rate was poor, with 5 patients experiencing tumour stabilisation and 10 progressing. Thus, the results do not support the further evaluation of RFS2000 as a single agent in patients with recurrent GBM.
authors.affiliation: Department of Medicine, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94815 Villejuif, France. raymond@igr.fr
authors.forename: E
authors.initials: E
authors.lastname: Raymond
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.forename: R
authors.initials: R
authors.lastname: Stupp
authors.forename: J
authors.initials: J
authors.lastname: Menten
authors.forename: P
authors.initials: P
authors.lastname: Chollet
authors.forename: T
authors.initials: T
authors.lastname: Lesimple
authors.forename: R
authors.initials: R
authors.lastname: Fety-Deporte
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: X
authors.initials: X
authors.lastname: Paoletti
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; C079905:rubitecan; D002166:Camptothecin