title: Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-α in advanced malignant melanoma.
abstract: BACKGROUND
  The effect of the addition of fotemustine and/or interferon (IFN) to standard therapy with dacarbazine alone in patients with advanced malignant melanoma was investigated in a multicenter, randomized 2x2 factorial design trial.
  
  
  METHODS
  A total of 260 patients were randomly assigned to one of four treatment groups: (A) fotemustine and dacarbazine repeated on 3-week cycle; (B) same treatment as (A) plus IFN-α2b three times per week; (C) dacarbazine alone repeated on 3-week cycle; (D) same treatment as (C) plus IFN-α2b three times per week. Two comparisons were planned to assess the efficacy of fotemustine (groups A+B vs. C+D) and IFN-α2b (groups A+C vs. B+D).
  
  
  RESULTS
  Addition of fotemustine did not significantly improve overall survival (OS) (p=0.28) or progression-free survival (PFS) (p=0.55); Hazard ratio (HR) for OS was 0.93 (95% CI 0.71-1.21). Similarly, addition of IFN-α2b did not improve OS (p=0.68) or PFS (p=0.65); HR for OS was 0.92 (95% CI 0.70-1.20). Overall response rate was not improved by the addition of either fotemustine (p=0.87) or IFN-α2b (p=0.57). The combination of all three drugs resulted in the highest occurrence of adverse events.
  
  
  CONCLUSIONS
  No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-α2b to dacarbazine.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01359956.
authors: Department of Melanoma, Istituto Nazionale Tumori Fondazione Pascale, Via Mariano Semmola, 80131, Naples, Italy.
authors: Antonio
authors: A
authors: Daponte
authors: Simona
authors: S
authors: Signoriello
authors: Luigi
authors: L
authors: Maiorino
authors: Bruno
authors: B
authors: Massidda
authors: Ester
authors: E
authors: Simeone
authors: Antonio Maria
authors: AM
authors: Grimaldi
authors: Corrado
authors: C
authors: Caracò
authors: Giuseppe
authors: G
authors: Palmieri
authors: Antonio
authors: A
authors: Cossu
authors: Gerardo
authors: G
authors: Botti
authors: Antonella
authors: A
authors: Petrillo
authors: Secondo
authors: S
authors: Lastoria
authors: Ernesta
authors: E
authors: Cavalcanti
authors: Pasquale
authors: P
authors: Aprea
authors: Nicola
authors: N
authors: Mozzillo
authors: Ciro
authors: C
authors: Gallo
authors: Giuseppe
authors: G
authors: Comella
authors: Paolo Antonio
authors: PA
authors: Ascierto
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008545:Melanoma / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D016019:Survival Analysis
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D003606:Dacarbazine; C054368:fotemustine
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