Letrozole, a new oral aromatase inhibitor for advanced breast cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate
Letrozole, a new oral aromatase inhibitor for advanced breast cancer: Double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate
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DOI：
10.1200/jco.1998.16.2.453
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发表时间：
1998-02-01
影响因子：
45.3
通讯作者：
Trunet, PF
中科院分区：
文献类型：
--
作者：
Dombernowsky, P;Smith, I;Trunet, PF
目的：比较两种剂量的来曲唑和醋酸甲地孕酮（MA）作为绝经后晚期乳腺癌患者既往用抗雌激素治疗的二线治疗。患者和方法：在一项双盲、多中心试验中，551例局部晚期、局部复发或转移性乳腺癌患者被随机分配到来曲唑2.5 mg （n = 174）、来曲唑0.5 mg （n = 188）或来曲唑160 mg （n = 189）每日一次。数据分析肿瘤反应和安全性变量vp至33个月的随访评估和vp至45个月的生存。结果：来曲唑2.5 mg总客观有效率（24%）明显高于MA （16%， logistic回归，P = 0.04）或来曲唑0.5 mg （13%, P = 0.004）。来曲唑2.5 mg组的客观反应持续时间明显高于MA组（Cox回归，P = 0.02）。来曲唑2.5 mg在治疗失败的时间上显著优于MA和来曲唑0.5 mg （P = 0.04和P = 0.002）。在进展时间方面，来曲唑2.5 mg优于来曲唑0.5 mg (P = 0.02)，但不优于MA （P = 0.07）。与来曲唑0.5 mg相比，来曲唑2.5 mg对总生存期有显著的剂量效应（P = 0.03）。来曲唑在严重不良反应、因耐受性差而停药、心血管副作用和体重增加方面的耐受性明显优于MA。结论：数据显示，来曲唑2.5 mg每日1次治疗绝经后晚期乳腺癌患者比MA更有效，耐受性更好。(C)美国临床肿瘤学会1998。
Purpose: to compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens.Patients and Methods: Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables vp to 33 months of follow-up evaluation and for survival vp to 45 months.Results: Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain.Conclusion: The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens. (C) 1998 by American Society of Clinical Oncology.