title: Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma.
abstract: Alkylating agents, such as temozolomide (TMZ) and fotemustine (FTM) are widely used in recurrent glioblastoma (GBM) regimes. Several strategies have been proposed to prevent resistance to these agents, by combining or sequencing them. We report the results of a pilot study of patients with refractory GBM receiving a regime of twice-daily dosing of temozolomide administered on day 1, (with an initial oral dose of 200 mg/m(2) and a second oral dose of 75 mg/m(2) 12 h later), followed by fotemustine in a single i.v. infusion at 75 mg/m(2) on day 2, repeated every four weeks. Enrolment was stopped at 15 patients due to lack of effectiveness of this schedule for patients with GBM. Toxicity was mild, with no grade 4 side effects reported. Results indicate that our temozolomide -FTM combined schedule is not effective, although well tolerated, in non responsive patients with GBM. Further strategies are required to improve the outcome of these patients.
authors.affiliation: Department of Medical Oncology, Polytechnic University of the Marche Region, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Umberto I-GM Lancisi and G Salesi, Ancona, Italy. mattymo@alice.it
authors.forename: M
authors.initials: M
authors.lastname: Santoni
authors.forename: A
authors.initials: A
authors.lastname: Paccapelo
authors.forename: L
authors.initials: L
authors.lastname: Burattini
authors.forename: A
authors.initials: A
authors.lastname: Onofri
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D000077204:Temozolomide
chemical_list: D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide