title: A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma.
abstract: In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m(2) every 2 weeks for five consecutive administrations (induction phase), and then every 4 weeks at 80 [DOSAGE ERROR CORRECTED] mg/m(2) as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0-10%], 9 partial responses (22.5%, 95% CI: 15-37%), and 16 stable diseases (40%, 95% CI: 32-51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9-9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile.
authors.affiliation: Oncology Department, "S. Giovanni di Dio" Hospital, ASL Napoli2 Nord Via Giovanni XXIII, 80028 Frattaminore, Naples, Italy. lelloaddeo@alice.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: M Serena
authors.initials: MS
authors.lastname: De Santi
authors.forename: Liliana
authors.initials: L
authors.lastname: Montella
authors.forename: Alberto
authors.initials: A
authors.lastname: Abbruzzese
authors.forename: Ciro
authors.initials: C
authors.lastname: Parlato
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Marco
authors.initials: M
authors.lastname: Carraturo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Faiola
authors.forename: Michele
authors.initials: M
authors.lastname: Genovese
authors.forename: Gregorio
authors.initials: G
authors.lastname: Cennamo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Del Prete
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016001:Confidence Intervals; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D009607:Nitrosourea Compounds / Q000008:administration & dosage*; D016017:Odds Ratio; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D000077204:Temozolomide; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide