title: A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy.
abstract: BACKGROUND
  At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed.
  
  
  METHODS
  Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment.
  
  
  RESULTS
  163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306).
  
  
  CONCLUSIONS
  FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.
authors.affiliation: Department of Medical Oncology, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Umberto I-GM Lancisi and G Salesi, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paccapelo
authors.forename: Ivan
authors.initials: I
authors.lastname: Lolli
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Fabrini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Silvano
authors.forename: Beatrice
authors.initials: B
authors.lastname: Detti
authors.forename: Franco
authors.initials: F
authors.lastname: Perrone
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Savio
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Erminio
authors.initials: E
authors.lastname: Bonizzoni
authors.forename: Tania
authors.initials: T
authors.lastname: Perrone
authors.forename: Silvia
authors.initials: S
authors.lastname: Scoccianti
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D000077204:Temozolomide; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide