title: Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of malignant glioma: a randomized phase II trial.
abstract: OBJECTIVE
  This study was a randomized, multicenter Phase II trial comparing the effect of perioperative implantation of 5-fluorouracil-releasing microspheres followed by early radiotherapy (Arm A) and early radiotherapy alone (Arm B) in patients with gross total resection of high-grade glioma.
  
  
  METHODS
  Patients were randomized on clinical and radiological assumption of supratentorial high-grade glioma. All patients underwent surgery, and after resection and histological confirmation, patients randomized to Arm A received multiple injections of microsphere suspension (130 mg of 5-fluorouracil). Conventional fractionated radiotherapy (59.4 Gy) was initiated between the second and the seventh day after surgery for both arms.
  
  
  RESULTS
  A total of 95 patients were randomized. Seventy-seven patients were treated and analyzed in intention to treat for efficacy and safety. Overall survival was 15.2 months in Arm A and 13.5 months in Arm B. In the subpopulation of patients with complete resection, overall survival was 15.2 months in Arm A versus 12.3 months in Arm B. However, these differences were not significant. Safety was acceptable with prophylactic high doses of corticosteroids.
  
  
  CONCLUSIONS
  It may be hypothesized that the implantation of 5-fluorouracil-loaded microspheres in the wall of the cavity resection did increase the overall survival, but the present study was not designed and sufficiently powered to demonstrate this.
authors.affiliation: Department of Neurosurgery, Institut National de la Santé et de la Recherche Médicale, Unite 646, University Hospital, Angers, France. phmenei@chu-angers.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Menei
authors.forename: Laurent
authors.initials: L
authors.lastname: Capelle
authors.forename: Jacques
authors.initials: J
authors.lastname: Guyotat
authors.forename: Stéphane
authors.initials: S
authors.lastname: Fuentes
authors.forename: Richard
authors.initials: R
authors.lastname: Assaker
authors.forename: Benoit
authors.initials: B
authors.lastname: Bataille
authors.forename: Patrick
authors.initials: P
authors.lastname: François
authors.forename: Didier
authors.initials: D
authors.lastname: Dorwling-Carter
authors.forename: Philippe
authors.initials: P
authors.lastname: Paquis
authors.forename: Luc
authors.initials: L
authors.lastname: Bauchet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Parker
authors.forename: Jean
authors.initials: J
authors.lastname: Sabatier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faisant
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001673:Biodegradation, Environmental; D003131:Combined Modality Therapy; D003692:Delayed-Action Preparations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D011838:Radiation-Sensitizing Agents; D005472:Fluorouracil