[Randomised phase III trial of fotemustine versus fotemustine plus whole brain irradiation in cerebral metastases of melanoma].
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.
Mornex
F
F
Centre hospitalier Lyon-Sud, service de radiothérapie-oncologie, EA 643, 69495 cedex, Pierre-Bénite, France. mornex@radiotherapie.univ-lyon.fr
Thomas
L
L
Mohr
P
P
Hauschild
A
A
Delaunay
M M
MM
Lesimple
T
T
Tilgen
W
W
Nguyen
B B
BB
Guillot
B
B
Ulrich
J
J
Bourdin
S
S
Mousseau
M
M
Cupissol
D
D
Bonneterre
J
J
de Gislain
C
C
Bensadoun
J R
JR
Clavel
M
M
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
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine