title: GEINOFOTE: efficacy and safety of fotemustine in patients with high-grade recurrent gliomas and poor performance status.
abstract: OBJECTIVE
  The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status.
  
  
  METHODS
  Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact.
  
  
  RESULTS
  In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment.
  
  
  CONCLUSIONS
  This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain. pedro.perez@salud.madrid.org.
authors.forename: P
authors.initials: P
authors.lastname: Pérez-Segura
authors.affiliation: Hospital 12 de octubre, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Manneh
authors.affiliation: Hospital Universitario, Canarias, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ceballos
authors.affiliation: Hospital Marqués de Valdecilla, Santander, Spain.
authors.forename: A
authors.initials: A
authors.lastname: García
authors.affiliation: Hospital Carlos Haya, Málaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Benavides
authors.affiliation: Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fuster
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Vaz
authors.affiliation: Hospital General, Ciudad Real, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Cano
authors.affiliation: Hospital Central, Asturias, Spain.
authors.forename: J P
authors.initials: JP
authors.lastname: Berros
authors.affiliation: Hospital Lucus Augusti, Lugo, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Covela
authors.affiliation: Hospital La Paz, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Moreno
authors.affiliation: Hospital Universitario, Elche, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Quintanar
authors.affiliation: Hospital General, Albacete, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: García Bueno
authors.affiliation: Complejo Hospitalario, Vigo, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Fernández
authors.affiliation: Hospital 12 de octubre, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sepúlveda
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine
keywords: Fotemustine; Glioblastoma; High-grade glioma; Poor PS; Relapse