title: Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study.
abstract: 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.
authors.affiliation: Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejiuf Cedex, France. avril@igr.fr
authors.forename: M F
authors.initials: MF
authors.lastname: Avril
authors.forename: S
authors.initials: S
authors.lastname: Aamdal
authors.forename: J J
authors.initials: JJ
authors.lastname: Grob
authors.forename: A
authors.initials: A
authors.lastname: Hauschild
authors.forename: P
authors.initials: P
authors.lastname: Mohr
authors.forename: J J
authors.initials: JJ
authors.lastname: Bonerandi
authors.forename: M
authors.initials: M
authors.lastname: Weichenthal
authors.forename: K
authors.initials: K
authors.lastname: Neuber
authors.forename: T
authors.initials: T
authors.lastname: Bieber
authors.forename: K
authors.initials: K
authors.lastname: Gilde
authors.forename: V
authors.initials: V
authors.lastname: Guillem Porta
authors.forename: J
authors.initials: J
authors.lastname: Fra
authors.forename: J
authors.initials: J
authors.lastname: Bonneterre
authors.forename: P
authors.initials: P
authors.lastname: Saïag
authors.forename: D
authors.initials: D
authors.lastname: Kamanabrou
authors.forename: H
authors.initials: H
authors.lastname: Pehamberger
authors.forename: J
authors.initials: J
authors.lastname: Sufliarsky
authors.forename: J L
authors.initials: JL
authors.lastname: Gonzalez Larriba
authors.forename: A
authors.initials: A
authors.lastname: Scherrer
authors.forename: Y
authors.initials: Y
authors.lastname: Menu
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine