在一项比较前列腺癌患者中基线特征分层的第 3 期试验（CS21）中，对生化复发率的次要终点的进一步分析，degarelix 80mg 对比亮丙瑞林。

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.

机构信息

Cliniques Universitaires Saint Luc/Université Catholique de Louvain, Brussels, Belgium.

出版信息

Eur Urol. 2010 May;57(5):836-42. doi: 10.1016/j.eururo.2009.11.029. Epub 2009 Nov 20.

DOI:10.1016/j.eururo.2009.11.029

PMID:19962227

Abstract

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 (<10, 10-20, >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.

摘要

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生存。

目的

比较degarelix 和亮丙瑞林在 PSA 无复发生存方面的疗效。

设计、地点和参与者：这是一项为期 1 年的、多中心、随机、开放标签的 3 期临床试验，比较了 240mg 剂量的 degarelix 用药 1 个月，然后每月 80mg（240/80mg）；240mg 剂量的 degarelix 用药 1 个月，然后每月 160mg；以及 7.5mg/mo 的亮丙瑞林的疗效和安全性。共有 610 名经组织学证实患有前列腺癌（所有阶段）且需要雄激素剥夺治疗的患者入组。该试验的主要终点先前已报告；本报告中报告的方案和探索性亚组分析重点是 240/80mg 的 degarelix（美国食品和药物管理局和欧洲药品管理局批准用于治疗激素初治晚期前列腺癌患者的剂量）。

测量

评估 PSA 无进展生存（与最低点相比连续两次 PSA 增加 50%，且至少相隔 2 周的两次连续测量 PSA 两次均≥5ng/ml 或死亡）和 PSA 变化。分析了基线疾病分期（局限性、局部进展性和转移性）和 PSA 水平（<10、10-20、>20-50 和>50ng/ml）的影响。

结果和局限性

与亮丙瑞林相比，接受 degarelix 治疗的患者 PSA 进展或死亡的风险显著降低（p=0.05）。PSA 复发主要发生在晚期疾病患者中，仅发生在基线 PSA>20ng/ml 的患者中。PSA>20ng/ml 的患者 PSA 复发的时间明显长于 degarelix（p=0.04）。每个亚组中患者数量相对较少是本研究的一个局限性。