title: Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group.
abstract: OBJECTIVE
  Temozolomide (TMZ) has shown efficacy in metastatic melanoma equal to that of dacarbazine (DTIC), the standard chemotherapeutic agent for melanoma. As the combination with interferon-alfa (IFN-alpha) appears superior to single-agent DTIC regarding response rates, the purpose of this study was to compare TMZ alone and TMZ plus IFN-alpha in terms of objective response (OR), overall survival, and safety in a prospective, randomized, multicenter trial.
  
  
  METHODS
  Two hundred ninety-four patients with untreated stage IV metastatic melanoma (American Joint Committee on Cancer staging system) were randomly assigned to receive either oral TMZ alone (200 mg/m2/day; days 1 through 5 every 28 days) or in combination with subcutaneous IFN-alpha (5 MU/m2; days 1, 3, and 5 every week).
  
  
  RESULTS
  Two hundred eighty-two patients were eligible for an intent-to-treat analysis, 271 patients were treated per protocol. In the TMZ + IFN-alpha arm, 33 (24.1%) of 137 patients responded to therapy (partial or complete remission) whereas in the monotherapy arm, in 18 (13.4%) of 134 patients, a response was evident. Thus, the response rate was significantly higher in the combination arm (P = .036). Median survival time was 8.4 months for patients treated with TMZ (95% CI, 7.07 to 9.27) and 9.7 months for those treated with the combination (95% CI, 8.26 to 11.18; P = .16). Dose modifications and interval prolongations due to hematologic toxicity were significantly more frequent in the TMZ + IFN-alpha arm (P < .001).
  
  
  CONCLUSIONS
  In metastatic melanoma treatment with TMZ + IFN-alpha leads to a significantly superior OR rate compared to treatment with TMZ alone, which did not translate into prolonged survival in our study population.
authors.affiliation: Department of Dermatology, J.W. Goethe-University, Frankfurt am Main, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: Konstanze
authors.initials: K
authors.lastname: Spieth
authors.forename: Ulrike
authors.initials: U
authors.lastname: Leiter
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Peter
authors.initials: P
authors.lastname: von den Driesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.forename: Ruthild
authors.initials: R
authors.lastname: Linse
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tilgen
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Günther
authors.initials: G
authors.lastname: Sebastian
authors.forename: Sven
authors.initials: S
authors.lastname: Krengel
authors.forename: Lutz
authors.initials: L
authors.lastname: Kretschmer
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D003606:Dacarbazine; D000077204:Temozolomide