title: Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group.
abstract: BACKGROUND
  Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma.
  
  
  METHODS
  Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m2 and cisplatin 30 mg/m2 on days 1 to 3 combined with interferon-alfa-2b 10 x 10(6) U/m2 subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 x 10(6) U/m2/6 hours, 18 x 10(6) U/m2/12 hours, 18 x 10(6) U/m2/24 hours, and 4.5 x 10(6) U/m2 for 3 x 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles.
  
  
  RESULTS
  Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%).
  
  
  CONCLUSIONS
  Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.
authors.affiliation: Department of Medicine III, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. ulrich.keilholz@medizin.fu-berlin.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.forename: Wim
authors.initials: W
authors.lastname: Kruit
authors.forename: Poulam
authors.initials: P
authors.lastname: Patel
authors.forename: Danielle
authors.initials: D
authors.lastname: Lienard
authors.forename: Jose
authors.initials: J
authors.lastname: Thomas
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Proebstle
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmittel
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Thierry
authors.initials: T
authors.lastname: Velu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Negrier
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kleeberg
authors.forename: Frederic
authors.initials: F
authors.lastname: Lehman
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D002945:Cisplatin / Q000627:therapeutic use; D003606:Dacarbazine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011336:Probability; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D012016:Reference Values; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D003606:Dacarbazine; D002945:Cisplatin