title: Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma.
abstract: Dacarbazine (DTIC) has been the mainstay of chemotherapy for metastatic melanoma for over two decades, but only 15%-20% of patients respond and benefit is usually transient. Randomized studies combining DTIC with interferon-alpha (IFN-alpha) in advanced disease have so far been inconclusive in terms of response and survival. We report a randomized prospective pilot Phase III trial of DTIC +IFN-alpha in patients with metastatic melanoma. The primary endpoint was death. A total of 61 patients were randomized between April 1995 and April 1998. Differences in survival between groups were assessed using log-rank analysis. Quality of life was measured using the European Organization for Research on Treatment of Cancer QLQ C30 (+3) questionnaire. Fifty-seven patients died during the study. The median survival for patients receiving DTIC was 7.2 months (95% confidence interval (CI) 4.4-9.0); it was 4.8 months for DTIC + IFN-alpha (95% CI 2.0-8.0). There was no significant difference in survival between the two treatment arms (chi2 unadjusted = 0.15, P = 0.70; chi2 adjusted = 0.01, P = 0.91). The 6-month survival of those patients randomized to DTIC alone was 58% compared with 40% for those patients randomized to DTIC + IFN-alpha. There were no differences in quality of life between treatment groups. This study failed to demonstrate a survival benefit for patients receiving IFN-alpha in combination with DTIC. These results are inconclusive primarily owing to the small size of the trial. A meta-analysis is required to determine whether there is a role for the addition of IFN-alpha to DTIC in the treatment of this disease.
authors.affiliation: CRC Trials Unit, Institute of Cancer Studies, The Medical School, Edgbaston, Birmingham, UK. a.young@bham.ac.uk
authors.forename: A M
authors.initials: AM
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: Marsden
authors.forename: A
authors.initials: A
authors.lastname: Goodman
authors.forename: A
authors.initials: A
authors.lastname: Burton
authors.forename: J A
authors.initials: JA
authors.lastname: Dunn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011788:Quality of Life; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015996:Survival Rate
chemical_list: D016898:Interferon-alpha; D003606:Dacarbazine