Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study.
OBJECTIVE
To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma.


METHODS
Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days).


RESULTS
Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n=229; 15.2% v 6.8%; P=.043) and in full analysis set (n=221) (15.5% v 7.2%; P=.053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P=.059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P=.067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms.


CONCLUSIONS
ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.
Avril
M F
MF
Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejiuf Cedex, France. avril@igr.fr
Aamdal
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S
Grob
J J
JJ
Hauschild
A
A
Mohr
P
P
Bonerandi
J J
JJ
Weichenthal
M
M
Neuber
K
K
Bieber
T
T
Gilde
K
K
Guillem Porta
V
V
Fra
J
J
Bonneterre
J
J
Saïag
P
P
Kamanabrou
D
D
Pehamberger
H
H
Sufliarsky
J
J
Gonzalez Larriba
J L
JL
Scherrer
A
A
Menu
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Y
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000453:epidemiology / Q000556:secondary; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine