title: Outcomes of patients with metastatic melanoma treated with molecularly targeted agents in phase I clinical trials.
abstract: BACKGROUND
  First-line treatment options utilizing chemotherapy and cytokine-based treatments for patients with metastatic melanoma (MM) are unsatisfactory. We analyzed the clinical outcomes of patients with MM treated in phase I trials of novel agents. We hypothesized that patients included in phase I clinical trials did not have worse outcomes than with the chemotherapy and cytokine-based first-line treatment.
  
  
  METHODS
  Data of patients with MM treated at The Drug Development Unit between 2004 and 2010 were collected. The response rate (RR) and time to progression (TTP) for first-line therapy were compared to those of phase I trial therapy. Patients acted as their own controls for statistical analyses.
  
  
  RESULTS
  Sixty-five patients were treated in 31 phase I trials. First-line treatment included dacarbazine or temozolomide in 58 (89%) cases and interferon-α in 5 patients (8%) and cisplatin-based treatment in 2 patients (3%). There was no significant difference in either the RR (11 vs. 14%, p = 0.87) or TTP (90 vs. 53 days, p = 0.15) in patients treated with first-line treatment versus phase I treatment, respectively.
  
  
  CONCLUSIONS
  Phase I clinical trials of molecularly targeted agents show clinical activity that is not dissimilar to that of treatment with existing chemotherapy and cytokine-based treatment.
authors: The Drug Development Unit, The Institute of Cancer Research, Sutton, UK.
authors: Montserrat
authors: M
authors: Blanco Codesido
authors: Andre
authors: A
authors: Tesainer Brunetto
authors: Sophia
authors: S
authors: Frentzas
authors: Victor
authors: V
authors: Moreno Garcia
authors: Dionysis
authors: D
authors: Papadatos-Pastos
authors: Joanna Vitfell
authors: JV
authors: Pedersen
authors: Leonardo
authors: L
authors: Trani
authors: Martina
authors: M
authors: Puglisi
authors: L Rhoda
authors: LR
authors: Molife
authors: Udai
authors: U
authors: Banerji
mesh_terms: D000328:Adult; D000368:Aged; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf