Additional Analysis of the Secondary End Point of Biochemical Recurrence Rate in a Phase 3 Trial (CS21) Comparing Degarelix 80 mg Versus Leuprolide in Prostate Cancer Patients Segmented by Baseline Characteristics
Additional Analysis of the Secondary End Point of Biochemical Recurrence Rate in a Phase 3 Trial (CS21) Comparing Degarelix 80 mg Versus Leuprolide in Prostate Cancer Patients Segmented by Baseline Characteristics
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DOI：
10.1016/j.eururo.2009.11.029
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发表时间：
2010-05-01
期刊：
影响因子：
23.4
通讯作者：
Persson, Bo-Eric
中科院分区：
文献类型：
--
作者：
Tombal, Bertrand;Miller, Kurt;Persson, Bo-Eric
背景：最近的数据表明前列腺特异性抗原 (PSA) 进展可能预测前列腺癌患者的总体生存率。目的：比较地加瑞克和亮丙瑞林在 PSA 无复发生存方面的活性。设计、设置和受试者：3 期、1 年、多中心、随机、开放标签试验，比较地加瑞克 240 mg 持续 1 个月，然后每月 80 mg（240/80 mg）的疗效和安全性；地加瑞克 240 mg，持续 1 个月，然后每月 160 mg；和亮丙瑞林 7.5 mg/mo。总体而言，纳入了 610 名经组织学证实患有前列腺癌（所有阶段）且需要接受雄激素剥夺治疗的患者。该试验的主要终点之前已报道过；本文报告的方案和探索性亚组分析重点关注 240/80 mg 地加瑞克（美国食品和药物管理局和欧洲医学评估协会批准的用于治疗未经激素治疗的晚期前列腺癌患者的剂量）。 测量：PSA 无进展生存期（与最低点相比，PSA 连续两次增加 50%，且两次连续测量相隔至少 2 周或死亡，PSA 连续两次增加 >= 5 ng/ml）和 PSA 变化。分析了基线疾病分期（局部、局部晚期和转移性）和 PSA 水平（20-50 和 >50 ng/ml）的影响。结果和局限性：与亮丙瑞林相比，接受地加瑞克治疗的患者 PSA 进展或死亡的风险显着降低（p = 0.05）。 PSA 复发主要发生在晚期疾病患者中，并且仅发生在基线 PSA >20 ng/ml 的患者中。 PSA > 20 ng/ml 的患者使用地加瑞克后 PSA 复发的时间显着延长 (p = 0.04)。每个亚组中患者数量相对较少是本研究的局限性。结论：这些结果产生了这样的假设：与亮丙瑞林相比，240/80 mg 地加瑞克可改善 PSA 控制。在这项为期一年的研究中，PSA 复发几乎全部发生在转移性前列腺癌或基线 PSA 较高的患者中。需要进一步的研究来证实这些发现。 (C) 2009 年欧洲泌尿外科协会。由 Elsevier B.V 出版。保留所有权利。
Background: Recent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients.Objective: To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival.Design, setting, and participants: Phase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo, and then 80 mg monthly (240/80 mg); degarelix at 240 mg for 1 mo, and then 160 mg monthly; and leuprolide at 7.5 mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer).Measurements: PSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and >= 5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (20-50, and >50 ng/ml) were analysed.Results and limitations: Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p = 0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p = 0.04). The relatively low number of patients in each subgroup is a limitation of this study.Conclusions: These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.