title: [Randomised phase III trial of fotemustine versus fotemustine plus whole brain irradiation in cerebral metastases of melanoma].
abstract: OBJECTIVE
  The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases.
  
  
  METHODS
  Seventy-six patients (instead of the 106 planned patients; study was stopped after the interim analysis) were randomised receiving either fotemustine (arm A, n = 39) or fotemustine and whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg m(-2) on day 1, 8 and 15, followed by a 5-week rest period, then every 3 weeks in non-progressive patients. In arm B, a concomitant whole brain irradiation was performed at the total dose of 37.5 Gy (2.5 Gy/d(-1), days 1-5, 3 consecutive weeks).
  
  
  RESULTS
  Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in brain response (arm A: 7.4%, B: 10.0%) or control rates (objective response plus stable disease) after seven weeks (arm A: 30%, B: 47%) and overall survival (arm A: 86d, B: 105d). However, there was a significant difference in favour of arm B for the time to brain progression (p = 0.028, Wilcoxon test).
  
  
  CONCLUSIONS
  Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival.
authors.affiliation: Centre hospitalier Lyon-Sud, service de radiothérapie-oncologie, EA 643, 69495 cedex, Pierre-Bénite, France. mornex@radiotherapie.univ-lyon.fr
authors.forename: F
authors.initials: F
authors.lastname: Mornex
authors.forename: L
authors.initials: L
authors.lastname: Thomas
authors.forename: P
authors.initials: P
authors.lastname: Mohr
authors.forename: A
authors.initials: A
authors.lastname: Hauschild
authors.forename: M M
authors.initials: MM
authors.lastname: Delaunay
authors.forename: T
authors.initials: T
authors.lastname: Lesimple
authors.forename: W
authors.initials: W
authors.lastname: Tilgen
authors.forename: B B
authors.initials: BB
authors.lastname: Nguyen
authors.forename: B
authors.initials: B
authors.lastname: Guillot
authors.forename: J
authors.initials: J
authors.lastname: Ulrich
authors.forename: S
authors.initials: S
authors.lastname: Bourdin
authors.forename: M
authors.initials: M
authors.lastname: Mousseau
authors.forename: D
authors.initials: D
authors.lastname: Cupissol
authors.forename: J
authors.initials: J
authors.lastname: Bonneterre
authors.forename: C
authors.initials: C
authors.lastname: de Gislain
authors.forename: J R
authors.initials: JR
authors.lastname: Bensadoun
authors.forename: M
authors.initials: M
authors.lastname: Clavel
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018450:Disease Progression; D005260:Female; D006801:Humans; D015993:Life Tables; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary*; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine