title: Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma.
abstract: BACKGROUND
  We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4(+)CD25(HI)Foxp3(+) regulatory T cells and expanded melanoma-specific CD8(+) T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.
  
  
  METHODS
  In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[(18)F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.
  
  
  RESULTS
  After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; p value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.
  
  
  CONCLUSIONS
  These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.
  
  
  BACKGROUND
  NCT00299689.
authors.affiliation: Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Sucheta
authors.initials: S
authors.lastname: Telang
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Rasku
authors.forename: Amy L
authors.initials: AL
authors.lastname: Clem
authors.forename: Karen
authors.initials: K
authors.lastname: Carter
authors.forename: Alden C
authors.initials: AC
authors.lastname: Klarer
authors.forename: Wesley R
authors.initials: WR
authors.lastname: Badger
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Milam
authors.forename: Shesh N
authors.initials: SN
authors.lastname: Rai
authors.forename: Jianmin
authors.initials: J
authors.lastname: Pan
authors.forename: Hana
authors.initials: H
authors.lastname: Gragg
authors.forename: Brian F
authors.initials: BF
authors.lastname: Clem
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.forename: Donald M
authors.initials: DM
authors.lastname: Miller
authors.forename: Jason
authors.initials: J
authors.lastname: Chesney
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007629:Kentucky; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D013601:T-Lymphocytes; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox