RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL COMPARING THE RESPONSE RATES OF CARMUSTINE, DACARBAZINE, AND CISPLATIN WITH AND WITHOUT TAMOXIFEN IN PATIENTS WITH METASTATIC MELANOMA

Purpose: We designed and conducted a randomized, double-blind, placebo -controlled trial to compare the response rates and survival of patien ts with metastatic melanoma who received carmustine (BCNU), dacarbazin e (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo, Patients and Methods: Eligible patients with metastatic melan oma 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 cisplat in 25 mg/m(2) IV daily on days 1 to 3 and on days 22 to 24 with placeb o every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughou t the remainder of the treatment cycle. Patients were treated on proto col 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 1999 and January 1 995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity, The overall response rate was 21% in the p lacebo group and 30% in the tamoxifen group (P = .187), Complete and p artial responses were 3% and 27%, respectively, for the tamoxifen grou p and 6% and 14%, respectively, for the placebo group, Poor performanc e status and liver involvement were associated with a reduced likeliho od to respond to treatment. Major toxicities were similar in both grou ps with no statistically significant difference in the rates of deep v ein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grad e 4 thrombocytopenia. Conclusion: These results demonstrate that the a ddition of high doses of tamoxifen to this chemotherapy regimen does n ot increase the response rate compared with chemotherapy alone in unse lected patients with metastatic melanoma. (C) 1996 by American Society of Clinical Oncology.