Patients and Methods: Eligible patients with metastatic melanoma received either BCNU 150 mg/m(2) intravenously (IV) on day 1, DTIC 220 mg/m(2) IV daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m(2) IV daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided).

Results: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity, The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187), Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group, Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia.

Conclusion: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma. (C) 1996 by American Society of Clinical Oncology.