title: Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).
abstract: BACKGROUND
  Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide.
  
  
  METHODS
  Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m(2)) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m(2)) every 3 weeks for < or =1 year.
  
  
  RESULTS
  Forty-three patients (29 M, 14 F; median age 51 years, range 34-68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9-33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5-7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients (P = 0.044); no significant difference was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively.
  
  
  CONCLUSIONS
  The findings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.
authors.affiliation: Department of Medical Oncology, Ospedale Bellaria-Maggiore, Bologna, Italy. alba.brandes@yahoo.it
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.forename: A
authors.initials: A
authors.lastname: Tosoni
authors.forename: E
authors.initials: E
authors.lastname: Franceschi
authors.forename: V
authors.initials: V
authors.lastname: Blatt
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: M
authors.initials: M
authors.lastname: Faedi
authors.forename: P
authors.initials: P
authors.lastname: Amistà
authors.forename: M
authors.initials: M
authors.lastname: Gardiman
authors.forename: R
authors.initials: R
authors.lastname: Labianca
authors.forename: C
authors.initials: C
authors.lastname: Bianchini
authors.forename: M
authors.initials: M
authors.lastname: Ermani
authors.forename: M
authors.initials: M
authors.lastname: Reni
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide