Rusthoven J J, Quirt I C, Iscoe N A, McCulloch P B, James K W, Lohmann R C, Jensen J, Burdette-Radoux S, Bodurtha A J, Silver H K, Verma S, Armitage G R, Zee B, Bennett K
Department of Medical Oncology, Hamilton Regional Cancer Centre, Ontario, Canada.
J Clin Oncol. 1996 Jul;14(7):2083-90. doi: 10.1200/JCO.1996.14.7.2083.
We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo.
Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. 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).
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.
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.
我们设计并开展了一项随机、双盲、安慰剂对照试验，以比较接受卡莫司汀（BCNU）、达卡巴嗪（DTIC）和顺铂联合他莫昔芬治疗的转移性黑色素瘤患者与接受相同化疗加安慰剂治疗的患者的缓解率和生存率。
符合条件的转移性黑色素瘤患者在第1天静脉注射（i.v.）BCNU 150 mg/m²，在第1至3天以及第22至24天每天静脉注射DTIC 220 mg/m²，在第1至3天以及第22至24天每天静脉注射顺铂25 mg/m²，每6周给予安慰剂，或者在化疗前7天每天口服他莫昔芬160 mg共7天，并在整个治疗周期的剩余时间内每天口服40 mg，同时接受相同的化疗。根据缓解类型，患者按方案接受最多三个周期的治疗。假设要得出他莫昔芬具有临床重要益处的结论，缓解率至少需提高20%，我们设计该研究时，在5%水平（双侧）检测到该差异的概率为80%。
1992年2月至1995年1月期间，共纳入211例患者，其中199例被认为可评估缓解情况和毒性。安慰剂组的总体缓解率为21%，他莫昔芬组为30%（P = 0.187）。他莫昔芬组的完全缓解和部分缓解分别为3%和27%，安慰剂组分别为6%和14%。身体状况差和肝脏受累与治疗缓解可能性降低相关。两组的主要毒性相似，深静脉血栓形成、肺血栓栓塞、4级中性粒细胞减少或4级血小板减少的发生率无统计学显著差异。
这些结果表明，在未选择的转移性黑色素瘤患者中，在该化疗方案中添加高剂量他莫昔芬与单纯化疗相比，并未提高缓解率。
