Phase III multicenter randomized trial of the dartmouth regimen versus dacarbazine in patients with metastatic melanoma
Phase III multicenter randomized trial of the dartmouth regimen versus dacarbazine in patients with metastatic melanoma
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DOI：
10.1200/jco.1999.17.9.2745
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发表时间：
1999-09-01
影响因子：
45.3
通讯作者：
Kirkwood, JM
中科院分区：
文献类型：
--
作者：
Chapman, PB;Einhorn, LH;Kirkwood, JM
目的：几项单机构II期试验报告称，达特茅斯方案（达卡巴嗪、顺铂、卡莫司汀和他莫昔芬）可在40%至50%的IV期黑色素瘤患者中诱导主要肿瘤缓解。本研究旨在比较达特茅斯方案与标准达卡巴嗪治疗IV期转移瘤患者的总生存时间、客观肿瘤反应率和毒性。在这项多中心III期试验中，240例可测量的IV期黑色素瘤患者随机接受达特茅斯方案治疗（达卡巴嗪220 mg/m2+顺铂25 mg/m2，第1 - 3天，卡莫司汀150 mg/m2，第1天，每隔一个周期，他莫昔芬10 mg口服，每日2次）或达卡巴嗪1,000 mg/m2。每3周重复治疗。观察患者的肿瘤反应，生存时间，和toxicity.Results：中位生存时间从随机化为7个月，25%的患者生存大于或等于1年。在意向治疗基础上进行分析或仅考虑231例合格且接受治疗的患者时，两个治疗组之间的生存时间无差异。在226例患者中可评估肿瘤缓解。达卡巴嗪的反应率为10.2%，而达特茅斯方案为18.5%（P = 0.09）。骨髓抑制，恶心/呕吐，疲劳显着更常见的达特茅斯arm.Conclusion：没有差异的生存时间，只有一个小的，统计学上不显着增加肿瘤反应的IV期黑色素瘤患者治疗的达特茅斯方案与达卡巴嗪相比，达卡巴嗪仍然是IV期黑色素瘤的参考标准治疗。(C)1999年，美国临床肿瘤学会。
Purpose: Several single-institution phase II trials have reported that the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) can induce major tumor responses in 40% to 50% of stage IV melanoma patients. This study was designed to compare the overall survival time, rate of objective tumor response, and toxicity of the Dartmouth regimen with standard dacar-bazine treatment in stage IV metanoma patients.Patients and Methods: In this multicenter phase ill trial, 240 patients with measurable stage IV melanoma were randomized to receive the Dartmouth regimen (dacarbazine 220 mg/m(2) and cisplatin 25 mg/m(2) days 1 to 3, carmustine 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 patients survived greater than or equal to 1 year. There was no difference in survival time between the two treatment arms when analysed on an intent-to-treat basis or when only the 231 patients who were both eligible and had received treatment were considered. Tumor response was assessable in 226 patients. 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, statistically nonsignificant increase in tumor response for stage IV melanoma patients treated with the Dartmouth regimen compared with dacarbazine, Dacarbazine remains the reference standard treatment for stage IV melanoma. (C) 1999 by American Society of Clinical Oncology.