Phase III multicenter randomized trial of the dartmouth regimen versus dacarbazine in patients with metastatic melanoma

Purpose: Several single-institution phase II trials have reported that the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) can i nduce major tumor responses in 40% to 50% of stage IV melanoma patients. Th is study was designed to compare the overall survival time, rate of objecti ve tumor response, and toxicity of the Dartmouth regimen with standard daca r-bazine treatment in stage IV metanoma patients. Patients and Methods: In this multicenter phase ill trial, 240 patients wit h measurable stage IV melanoma were randomized to receive the Dartmouth reg imen (dacarbazine 220 mg/m(2) and cisplatin 25 mg/m(2) days 1 to 3, carmust ine 150 mg/m(2) day 1 every other cycle, and tamoxifen 10 mg orally bid) or dacarbazine 1,000 mg/m(2). Treatment was repeated every 3 weeks. Patients were observed for tumor response, survival time, and toxicity. Results: Median survival time from randomization was 7 months; 25% of the p atients survived greater than or equal to 1 year. There was no difference i n survival time between the two treatment arms when analysed on an intent-t o-treat basis or when only the 231 patients who were both eligible and had received treatment were considered. Tumor response was assessable in 226 pa tients. The response rate to dacarbazine was 10.2% compared with 18.5% for the Dartmouth regimen (P = .09). Bone marrow suppression, nausea/vomiting, and fatigue were significantly more common in the Dartmouth arm. Conclusion: There was no difference in survival time and only a small, stat istically nonsignificant increase in tumor response for stage IV melanoma p atients treated with the Dartmouth regimen compared with dacarbazine, Dacar bazine remains the reference standard treatment for stage IV melanoma. (C) 1999 by American Society of Clinical Oncology.