A phase III randomized trial of dacarbazine and carboplatin with and without tamoxifen in the treatment of patients with metastatic melanoma

BACKGROUND: Metastatic melanoma is a disease associated with a poor prognosis, and dacarbazine is still the reference agent. The authors conducted a randomized trial to test the benefit of adding tamoxifen to dacarbazine and carboplatin chemotherapy for previously untreated patients with metastatic melanoma. METHODS: Eligible patients with histologically confirmed, measurable metastatic melanoma were randomized to carboplatin 300 mg/m2 and dacarbazine 1 g/m2 administered intravenously on Day 1 with or without tamoxifen 20 mg/day administered orally throughout the treatment period (C + D +/- T). Chemotherapy was repeated in 28-day treatment cycles for a minimum of 2 cycles or until disease progression. The study was designed to be stopped after accrual of 28 patients per treatment arm based on 80% power to detect an improvement in response from 20% to 40% among patients treated with tamoxifen. RESULTS: A total of 56 patients were randomized; all were evaluable for response and survival. The 2 treatment groups were well balanced for various prognostic factors; 75% of patients had predominant visceral disease. Complete and partial responses combined were 10.7% in the C + D arm and 14.3% in the C + D + T arm (P=1.0). Median survival was 7 months for C + D and 4.6 months for C + D + T (the difference was not significant). The median time to disease progression was worse for the patients treated with tamoxifen (P=0.03). Toxicity was similar in the two groups, with no episodes of deep venous thrombosis. CONCLUSIONS: The addition of tamoxifen did not improve the response rate, time to progression, or survival compared with chemotherapy with dacarbazine and carboplatin in unselected patients with metastatic melanoma.