title: A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma.
abstract: BACKGROUND
  Several trials demonstrated efficacy of the gemcitabine/treosulfan (GeT) combination in metastatic uveal melamoma. This randomized phase II trial compared the GeT combination versus treosulfan alone (T) in this rare disease.
  
  
  METHODS
  Chemotherapy-naive patients with proven metastatic uveal melanoma were randomly assigned to receive 1000 mg/m(2) of gemcitabine plus 3500 mg/m(2) of treosulfan (GeT) or 3500 mg/m(2) of T. Chemotherapy was administered on days 1 and 8 in both arms, cycles were repeated on day 29. Primary end point was rate of responses and disease stabilizations.
  
  
  RESULTS
  Forty-eight patients were randomized. Seven confirmed stable diseases (SDs) and one partial remission (PR) were observed in 24 patients treated with the GeT regimen, whereas no PR and only three SDs were observed in the T arm (P = 0.08). Median progression-free survival (PFS) was 3 months (95% CI 1.1-4.9) and 2 months (95% CI 1.7-2.3) in the GeT and T arm (P = 0.008, log-rank). Six and 12 months PFS was 34.8% and 17.9% and 16.7% and 0% always favoring the GeT arm.
  
  
  CONCLUSIONS
  This first randomized trial in metastatic uveal melanoma showed a superior PFS and a trend for a higher response/stabilization rate of the GeT combination over T.
authors.affiliation: Department of Internal Medicine III (Hematology, Oncology and Transfusion Medicine), Campus Benjamin Franklin, Berlin, Germany. alexander.schmittel@charite.de
authors.forename: A
authors.initials: A
authors.lastname: Schmittel
authors.forename: M
authors.initials: M
authors.lastname: Schmidt-Hieber
authors.forename: P
authors.initials: P
authors.lastname: Martus
authors.forename: N E
authors.initials: NE
authors.lastname: Bechrakis
authors.forename: R
authors.initials: R
authors.lastname: Schuster
authors.forename: J M
authors.initials: JM
authors.lastname: Siehl
authors.forename: M H
authors.initials: MH
authors.lastname: Foerster
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D016019:Survival Analysis; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; C018404:treosulfan; D002066:Busulfan; D000093542:Gemcitabine