Phase III clinical trial of the combination of cisplatin, dacarbazine, andcarmustine with or without tamoxifen in patients with advanced malignant melanoma

Purpose: A prospective randomized phase III clinical trial was conducted to assess whether the addition of tamoxifen (TAM) to the three-agent regimen of cisplatin (CDDP), dacarbazine (DTIC), and carmustine (BCNU) significantl y increased the progression-free survival and overall survival of patients with advanced malignant melanoma. Patients and Methods: Patients with advanced malignant melanoma were treate d with CDDP + DTIC + BCNU (CDB) with or without TAM. The dose schedule was CDDP 25 mg/m(2) given intravenously (IV) for 30 to 45 minutes in 500 mt of dextrose and 1/2 normal saline (NS) on days 1 to 3 of a 3-week cycle; DTIC 220 mg/m(2) IV for 1 hour in 500 mt of dextrose and 1/2 NaCl on days 1 to 3 of a 3-week cycle; BCNU 150 mg/m(2) IV for 2 to 3 hours in 750 to 1,000 mt of dextrose and 5% water on day 1 of every odd 3-week cycle; and TAM 20 mg taken orally every morning. Results: There were 184 eligible patients enrolled. These patients were obs erved until death or for a minimum of 1.3 years. At last contact 12 were st ill alive. The median rime ta progression was 3.4 months on the CDB arm and 3.1 months on the CDB + BAM arm. The median survival time wets 6.8 months with CDB and 6.9 months with CDB + TAM. Progression-free survival (P = .429 ) and overall. survival (P = .545) were not found to differ by treatment. Conclusion: The addition of TAM to this three-agent regimen of CDB was not found to provide a meaningful clinical advantage in the treatment of patien ts with advanced malignant melanoma. (C) 1999 by American Society of Clinical Oncology.