Significant and Sustained Antitumor Activity in Post-Docetaxel, Castration-Resistant Prostate Cancer With the CYP17 Inhibitor Abiraterone Acetate
Significant and Sustained Antitumor Activity in Post-Docetaxel, Castration-Resistant Prostate Cancer With the CYP17 Inhibitor Abiraterone Acetate
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DOI：
10.1200/jco.2009.24.6819
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发表时间：
2010-03-20
影响因子：
45.3
通讯作者：
de Bono, Johann S.
中科院分区：
文献类型：
--
作者：
Reid, Alison H. M.;Attard, Gerhardt;de Bono, Johann S.
PurposeThe的主要目的，这项试验是评估阿比特龙醋酸酯，一种口服的，特异性的，不可逆的抑制剂CYP 17在紫杉醇治疗的去势抵抗性前列腺癌（CRPC）患者的抗肿瘤活性。患者和方法在这个多中心，两个阶段，第二阶段的研究，阿比特龙醋酸酯1,000毫克，每天一次连续给药。主要终点是35名患者中至少7名患者的前列腺特异性抗原（PSA）下降≥ 50%。根据获得的II期设计，如果满足主要终点，则可以招募超过35例患者。次要目的包括：PSA下降>= 30%和>= 90%; RECIST（实体瘤反应评价标准）反应率和研究持续时间; PSA进展时间;安全性和耐受性;和循环肿瘤细胞（CTC）enumeration. ResultsDocetaxel治疗的CRPC患者（N = 47）。PSA下降>= 30%、>= 50%和>= 90%的患者分别为68%（32/47）、51%（24/47）和15%（7/47）。30例可测量疾病患者中有8例（27%）报告了部分缓解（根据RECIST）。至PSA进展的中位时间为169天（95% CI，113 - 281天）。中位研究周数为24周，47例患者中有12例（25.5%）继续研究≥ 48周。在34例患者中计数了CTC; 34例患者中的27例（79%）在基线时至少有5个CTC。27例患者中有11例（41%）的CTC从至少5个下降到少于5个，27例患者中有18例（67%）在开始醋酸阿比特龙治疗后CTC下降>= 30%。结论醋酸阿比特龙对多西他赛治疗后的CRPC患者具有显著的抗肿瘤活性。醋酸阿比特龙的随机III期试验正在进行中，以确定该药物的未来作用。
PurposeThe 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).Patients and MethodsIn 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 >= 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 >= 30% and >= 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.ResultsDocetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of >= 30%, >= 50% and >= 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 >= 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 >= 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated.ConclusionAbiraterone 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.