title: A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma.
abstract: The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with 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, Pierre-Benite Cedex, France. mornex@radiotherapie.univ-lyon1.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 N
authors.initials: BN
authors.lastname: Bui
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: M E
authors.initials: ME
authors.lastname: Bonneterre
authors.forename: C
authors.initials: C
authors.lastname: De Gislain
authors.forename: R J
authors.initials: RJ
authors.lastname: Bensadoun
authors.forename: M
authors.initials: M
authors.lastname: Clavel
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine