A Phase I and pharmacokinetic study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma

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Abstract
BACKGROUND The authors have previously demonstrated that tamoxifen (TAM) is synergistic with cisplatin (DDP) in patients with metastatic melanoma. In vitro studies have demonstrated that TAM/DDP synergy is dependent on a TAM effect that is currently under investigation. In an attempt to improve the complete response rate of this regimen, the authors initiated a Phase I trial to determine the maximum tolerated dose (MTD) of TAM that could be safely administered with weekly DDP. METHODS TAM was started on Day 1 at a dose of 80 mg/day and was increased by 40 mg to the MTD in groups of 3 patients. DDP (80 mg/m2) was begun on Day 2 and repeated weekly for a total of 3 weeks. During Week 4, the patients were not treated with DDP but instead evaluated for response. If disease stabilization or regression was documented, the patients received a second 3‐week cycle of DDP and were then reevaluated for response. Patients with progressive disease were removed from the study. RESULTS In 25 consecutive patients, the overall response rate was 20%. No responses were observed in patients treated with TAM at a dose of Cancer 1997; 79:1037‐43. © 1997 American Cancer Society.