title: Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma.
abstract: OBJECTIVE
  Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone. In an attempt to confirm this hypothesis, a randomized study was performed with the further intent of observing whether low doses of recombinant interferon alfa-2a (rIFN alpha 2a) could be as effective as intermediate doses.
  
  
  METHODS
  Two hundred sixty-six patients were randomized onto three different treatment arms: DTIC 800 mg/m2 intravenously (IV) days 1 and 21; DTIC plus rIFN alpha 2a 9 mIU intramuscularly (IM) daily; and DTIC plus rIFN alpha 2a 3 mIU IM three times per week. Major prognostic factors were well balanced among the three arms. Chemotherapy was administered for a maximum of eight cycles. After 6 months of therapy, rIFN alpha 2a was continued until disease progression at 3 mIU three times per week in responding patients who had received the combined treatment.
  
  
  RESULTS
  The percentage of objective responses did not differ among the three groups (20%, 28%, and 23%, respectively), although a significant prolongation of response duration was observed when rIFN alpha 2a was added to DTIC (2.6 v 8.4 v 5.5 months, respectively). However, this improvement in response duration did not translate into an amelioration of overall survival. The addition of rIFN alpha 2a led to the onset of flu-like syndrome, but in no case was it necessary to withdraw the treatment program and no toxic deaths or life-threatening toxicities were reported.
  
  
  CONCLUSIONS
  In this study, rIFN alpha 2a significantly prolonged response duration, whereas no effects on response rate and survival were observed; rIFN alpha 2a 3 mIU appeared to be equally effective and better tolerated than 9 mIU.
authors.affiliation: Biological Response Modifier in Melanoma, Italian Cooperative Group, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan.
authors.forename: E
authors.initials: E
authors.lastname: Bajetta
authors.forename: A
authors.initials: A
authors.lastname: Di Leo
authors.forename: M G
authors.initials: MG
authors.lastname: Zampino
authors.forename: M R
authors.initials: MR
authors.lastname: Sertoli
authors.forename: G
authors.initials: G
authors.lastname: Comella
authors.forename: M
authors.initials: M
authors.lastname: Barduagni
authors.forename: B
authors.initials: B
authors.lastname: Giannotti
authors.forename: P
authors.initials: P
authors.lastname: Queirolo
authors.forename: G
authors.initials: G
authors.lastname: Tribbia
authors.forename: M G
authors.initials: MG
authors.lastname: Bernengo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003606:Dacarbazine