The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
J Clin Oncol. 2010 Mar 20;28(9):1489-95. doi: 10.1200/JCO.2009.24.6819. Epub 2010 Feb 16.
The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC).
In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of > or = 50% in at least seven of 35 patients. Per an attained phase II design, more than 35 patients could be enrolled if the primary end point was met. Secondary objectives included: PSA declines of > or = 30% and > or = 90%; rate of RECIST (Response Evaluation Criteria in Solid Tumors) responses and duration on study; time to PSA progression; safety and tolerability; and circulating tumor cell (CTC) enumeration.
Docetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of > or = 30%, > or = 50% and > or = 90% were seen in 68% (32 of 47), 51% (24 of 47), and 15% (seven of 47) of patients, respectively. Partial responses (by RECIST) were reported in eight (27%) of 30 patients with measurable disease. Median time to PSA progression was 169 days (95% CI, 113 to 281 days). The median number of weeks on study was 24, and 12 (25.5%) of 47 patients remained on study > or = 48 weeks. CTCs were enumerated in 34 patients; 27 (79%) of 34 patients had at least five CTCs at baseline. Eleven (41%) of 27 patients had a decline from at least five to less than 5 CTCs, and 18 (67%) of 27 had a > or = 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated.
Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent.
本试验的主要目的是评估醋酸阿比特龙在多西他赛治疗的去势抵抗性前列腺癌（CRPC）患者中的抗肿瘤活性，醋酸阿比特龙是一种口服、特异性、不可逆的 CYP17 抑制剂。
在这项多中心、两阶段、II 期研究中，阿比特龙醋酸 1000mg 每日一次连续给药。主要终点是在至少 35 名患者中的 7 名中实现前列腺特异性抗原（PSA）下降≥50%。根据达到的 II 期设计，如果主要终点达到，可以招募超过 35 名患者。次要目标包括：PSA 下降≥30%和≥90%；RECIST（实体瘤反应评价标准）应答率和研究时间；PSA 进展时间；安全性和耐受性；以及循环肿瘤细胞（CTC）计数。
入组了 47 名接受多西他赛治疗的 CRPC 患者。PSA 下降≥30%、≥50%和≥90%的患者分别为 68%（32/47）、51%（24/47）和 15%（7/47）。有可测量疾病的 30 名患者中的 8 名（27%）报告了部分缓解（根据 RECIST）。PSA 进展的中位时间为 169 天（95%CI，113-281 天）。中位研究时间为 24 周，47 名患者中有 12 名（25.5%）>或=48 周仍在研究中。34 名患者中计数了 CTC；34 名患者中有 27 名（79%）基线时至少有 5 个 CTC。27 名患者中有 11 名（41%）从至少 5 个降至<5 个 CTC，27 名患者中有 18 名（67%）在开始用阿比特龙醋酸治疗后 CTC 下降≥30%。阿比特龙醋酸耐受良好。
醋酸阿比特龙在多西他赛治疗的 CRPC 患者中具有显著的抗肿瘤活性。正在进行醋酸阿比特龙的随机、III 期试验，以确定该药物的未来作用。
