title: Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG).
abstract: BACKGROUND
  Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNalpha-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation.
  
  
  METHODS
  In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 mug peg-IFNalpha-2b s.c. per week and oral TMZ 200 mg/m(2) (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety.
  
  
  RESULTS
  In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%.
  
  
  CONCLUSIONS
  The efficacy of TMZ plus peg-IFNalpha-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNalpha-2b seems to be similar to non-peg-IFN when combined with TMZ.
authors.affiliation: Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. konstanze.spieth@kgu.de
authors.forename: K
authors.initials: K
authors.lastname: Spieth
authors.forename: R
authors.initials: R
authors.lastname: Kaufmann
authors.forename: R
authors.initials: R
authors.lastname: Dummer
authors.forename: C
authors.initials: C
authors.lastname: Garbe
authors.forename: J C
authors.initials: JC
authors.lastname: Becker
authors.forename: A
authors.initials: A
authors.lastname: Hauschild
authors.forename: W
authors.initials: W
authors.lastname: Tilgen
authors.forename: S
authors.initials: S
authors.lastname: Ugurel
authors.forename: M
authors.initials: M
authors.lastname: Beyeler
authors.forename: E B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: K C
authors.initials: KC
authors.lastname: Kaehler
authors.forename: C
authors.initials: C
authors.lastname: Pföhler
authors.forename: J
authors.initials: J
authors.lastname: Gille
authors.forename: U
authors.initials: U
authors.lastname: Leiter
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D003606:Dacarbazine; C417083:peginterferon alfa-2b; D000077204:Temozolomide