Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone
Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone
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DOI：
10.1200/jco.2010.33.7675
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发表时间：
2012-02-20
影响因子：
45.3
通讯作者：
Logothetis, Christopher J.
中科院分区：
文献类型：
--
作者：
Efstathiou, Eleni;Titus, Mark;Logothetis, Christopher J.
目的雄激素信号持续存在与去势抵抗性前列腺癌（CRPC）进展有关。这项研究的目的是评估雄激素信号在骨髓浸润癌和睾酮在血液和骨髓中，并与临床observations.Patients和MethodsThis是一个开放标签，观察性研究57例骨转移CRPC谁接受transliac骨髓活检2007年10月至2010年3月之间。患者接受口服醋酸阿比特龙（1 g）每日一次和泼尼松（5 mg）每日两次。雄激素受体（AR）和CYP 17的表达进行了评估免疫组化，睾酮浓度质谱，AR拷贝数聚合酶链反应，荧光原位杂交在可用tissues.ResultsMedian总生存期为555天（95%CI，440至965+天）和TMPRSS 2-ERG状态。56例患者中有28例（50%）发生最大前列腺特异性抗原下降>= 50%。在25例骨髓样本有肿瘤浸润的患者中，AR的均匀、强核表达与>= 10%的CYP 17肿瘤表达相结合，与较长的停药时间（> 4个月）相关。治疗前CYP 17肿瘤表达>= 10%与骨髓穿刺睾酮增加相关。血液和骨髓穿刺睾酮浓度下降到低于皮克每毫升的水平，并保持抑制在progress.ConclusionThe观察到的预处理雄激素信号的签名是一致的持续雄激素信号在CRPC骨转移。这是醋酸阿比特龙在血液和骨髓抽吸物中实现睾酮持续抑制至低于皮克/毫升水平的第一个证据。血液与骨髓穿刺液的潜在混合限制了我们确定所测睾酮来源的能力。J Clin Oncol 30：637-643. (c)2011年美国临床肿瘤学会
PurposePersistent androgen signaling is implicated in castrate-resistant prostate cancer (CRPC) progression. This study aimed to evaluate androgen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations.Patients and MethodsThis was an open-label, observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010. Patients received oral abiraterone acetate (1 g) once daily and prednisone (5 mg) twice daily. Androgen receptor (AR) and CYP17 expression were assessed by immunohistochemistry, testosterone concentration by mass spectrometry, AR copy number by polymerase chain reaction, and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues.ResultsMedian overall survival was 555 days (95% CI, 440 to 965+ days). Maximal prostate-specific antigen decline >= 50% occurred in 28 (50%) of 56 patients. Homogeneous, intense nuclear expression of AR, combined with >= 10% CYP17 tumor expression, was correlated with longer time to treatment discontinuation (> 4 months) in 25 patients with tumor-infiltrated bone marrow samples. Pretreatment CYP17 tumor expression >= 10% was correlated with increased bone marrow aspirate testosterone. Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression.ConclusionThe observed pretreatment androgen-signaling signature is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels. Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone. J Clin Oncol 30:637-643. (c) 2011 by American Society of Clinical Oncology