Serum Androgens as Predictors of Survival in Metastatic Prostate Cancer

 描述(申请人提供)：这项研究的主要目标是证明去势抵抗前列腺癌(CRPC)患者的血清雄激素(SA)水平是总存活率(OS)的预后。在两个III期随机研究中观察到较高的SA与改善存活率的关系，而不考虑治疗方案，但从未在雄激素合成抑制剂(ASI)如阿比特龙或酮康唑不作为治疗一部分的研究中观察到。患者血清来自CALGB 90401--NCI赞助的合作小组随机第三阶段，在CRPC中比较多西紫杉醇/强的松(DP)和多西紫杉醇/强的松加贝伐单抗(DPB)。来自这项已完成研究的库存血清将用于通过CLIA认证的超灵敏(液相色谱串联质谱仪)技术测量雄激素水平，这些结果将与成熟患者的生存和结果数据相关联。这项工作的基本假设是，无论治疗如何，较高的血清雄激素与包括生存在内的结果的改善有关，因为它反映了更有利的生物学里程碑，即肿瘤仍部分依赖雄激素。我们有以下具体目标：目的1：评估在基线水平用超灵敏的方法测定血清雄激素(雄烯二酮、硫酸脱氢表雄酮和睾酮)是否能预测和预测接受CALGB 90401治疗的mCRPC患者的临床结果。目的：评估90401治疗前mCRPC患者SA从基线到疾病进展时间的一系列变化是否能预测OS的预后。目的3：建立整合SA水平的男性mCRPC患者OS的预后模型。这项建议是第一次对SA在接受DP、标准护理化疗的初治mCRPC患者的化疗中可以预测和预测OS的假设进行检验。一个积极的发现将证实雄激素信号的重要性，即使在正在接受一线化疗的非常晚期的疾病的背景下。这项工作的含义是，SA可能是CRPC患者预后的一个未被认识的决定因素，在设计靶向或风险适应治疗时应予以考虑。此外，这种分析的使用可以为临床决策提供信息，因为我们的初步数据表明，治疗前的SA水平可能预测治疗反应。由于90401是一项化疗研究，没有使用雄激素合成抑制剂，验证这些发现将表明SA可以预测和预测CRPC的预后，而不考虑治疗。

 DESCRIPTION (provided by applicant): The primary objective of this research is to demonstrate that serum androgen (SA) levels in patients with castration resistant prostate cancer (CRPC) are prognostic of overall survival (OS). A relationship of higher SA to improved survival has been observed in two phase III randomized studies, regardless of treatment arm, but never in a study in which an androgen synthesis inhibitor (ASI) such as abiraterone or ketoconazole was NOT part of the therapy. Patient serum is banked from CALGB 90401 - an NCI sponsored cooperative group randomized phase III that compared docetaxel plus prednisone (DP) to docetaxel/prednisone plus bevacizumab (DPB) in CRPC. Banked serum from this completed study will be used to measure androgen levels via CLIA certified ultrasensitive (liquid chromatography tandem mass spectroscopy) technique and these results will be associated with mature patient survival and outcome data. The underlying hypothesis of this work is that higher serum androgens are associated with improved outcomes, including survival, regardless of treatment, as it reflects a more favorable biological mileu in which the tumor remains partially dependent on androgens. We have the following specific aims: AIM 1: To assess whether serum androgens (Androstenedione, DHEA-sulfate and Testosterone) using an ultrasensitive assay at baseline will be prognostic and predictive for clinical outcomes in mCRPC patients treated on CALGB 90401. AIM 2: To evaluate whether serial changes in SA from baseline to the time of disease progression in mCRPC patients treated on 90401 are prognostic for OS. AIM 3: To develop a prognostic model for OS for men with mCRPC that integrates SA levels. This proposal is the first analysis to test the hypothesis that SA is prognostic and predictive of OS in chemotherapy-naïve mCRPC patients treated with DP, standard of care chemotherapy. A positive finding will confirm the importance of androgen signaling even in the setting of very advanced disease that is being treated with first-line chemotherapy. The implications of this work are that SA could be an unappreciated determinant of outcome in patients with CRPC and should be considered in the design of targeted or risk-adapted therapies. Further, the use of this analysis could inform clinical decision-making, as our preliminary data have shown that pre-treatment SA levels may be predictive of treatment response. Since 90401 was a study of chemotherapy and did not utilize an androgen synthesis inhibitor, validating these findings would suggest that SA are prognostic and predictive of outcomes in CRPC regardless of treatment.