title: Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882).
abstract: BACKGROUND
  In a previous randomised EORTC study on adjuvant dibromodulcitol (DBD) and bichloroethylnitrosourea (BCNU) in adults with glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), a clinically significant trend towards a longer overall survival (OS) and a progression-free survival (PFS) was observed in the subgroup of AA. The aim of the present study was to test this adjuvant regimen in a larger number of AA patients.
  
  
  METHODS
  Continuation of the previous phase III trial for newly diagnosed AA according to the local pathologist. Patients were randomised to either radiotherapy only or to radiotherapy in combination with BCNU on day 2 and weekly DBD, followed by adjuvant DBD and BCNU in cycles of six weeks for a maximum total treatment duration of one year. OS was the primary end-point.
  
  
  RESULTS
  Patients (193 ) with newly diagnosed AA according to local pathological assessment were randomised to radiotherapy (RT) alone (n=99), or to RT plus DBD/BCNU (n=94); 12 patients were considered not eligible. At central pathology review, over half (53%) of the locally diagnosed AA cases could not be confirmed. On intent-to-treat analysis, no statistically significant differences in OS (p=0.111) and PFS (p=0.087) were observed, median OS after RT was only 23.9 months 95% confidence interval (CI), [18.4-34.0] after RT plus DBD/BCNU 27.3 months 95% CI [21.4-46.8].
  
  
  CONCLUSIONS
  No statistically significant improvement in survival was observed after BCNU/DBD adjuvant chemotherapy in AA patients. The trend towards improved survival is consistent with previous reports. Central pathology review of grade 3 tumours remains crucial.
authors.affiliation: Hopital Universitaire Erasme, Brussels, Belgium.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Hildebrand
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Dénes
authors.initials: D
authors.lastname: Afra
authors.forename: Marc
authors.initials: M
authors.lastname: Frenay
authors.forename: Antonio
authors.initials: A
authors.lastname: Omuro
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Denis
authors.initials: D
authors.lastname: Lacombe
authors.forename: Anouk
authors.initials: A
authors.lastname: Allgeier
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000532:radiotherapy; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008936:Mitolactol / Q000008:administration & dosage / Q000009:adverse effects; D017211:Treatment Failure
chemical_list: D008936:Mitolactol; D002330:Carmustine