Serum Androgens as Predictors of Survival in Metastatic Prostate Cancer

血清雄激素作为转移性前列腺癌生存的预测因子

• 批准号: 8881946
• 负责人: SUSAN HALABI
• 金额: $ 19.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-05 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8881946
• 关键词: Androgens; Androstenedione; Biological; Biological Assay; Cancer and Leukemia Group B; Clinical; Data; Dehydroepiandrosterone Sulfate; Disease Progression; Eligibility Determination; Ketoconazole; Liquid Chromatography; Mass Spectrum Analysis; Measures; Metastatic Prostate Cancer; Outcome; Outcome Study; Patients; Phase; Prednisone; Randomized; Research; Risk; Serum; Signal Transduction; Stratification; Techniques; Testing; Testosterone; Therapeutic; Time; Treatment Failure; Work; abiraterone; advanced disease; arm; bevacizumab; castration resistant prostate cancer; chemotherapy; clinical decision-making; design; docetaxel; improved; inhibitor/antagonist; liquid chromatography mass spectrometry; men; phase 3 study; predictive modeling; prognostic; public health relevance; response; serum PSA; standard of care; treatment response; trial design; tumor

 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.

 描述（由申请方提供）：本研究的主要目的是证明去势抵抗性前列腺癌（CRPC）患者的血清雄激素（SA）水平可预测总生存期（OS）。在两项III期随机研究中观察到SA升高与生存期改善的关系，无论治疗组如何，但在雄激素合成抑制剂（ASI）（如阿比特龙或酮康唑）不是治疗的一部分的研究中从未观察到SA升高与生存期改善的关系。患者血清来自CALGB 90401 -NCI申办的合作组随机III期，比较多西他赛加泼尼松（DP）与多西他赛/泼尼松加贝伐珠单抗（DPB）治疗CRPC。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）技术测量雄激素水平，这些结果将与成熟的患者生存和结局数据相关。这项工作的基本假设是，较高的血清雄激素与改善的结果相关，包括生存率，无论治疗如何，因为它反映了一个更有利的生物环境，其中肿瘤仍然部分依赖于雄激素。我们有以下具体目标：目的1：评估在基线时使用超灵敏测定法测定血清雄激素（雄烯二酮、硫酸脱氢表雄酮和替吉奥）是否可预测接受CALGB 90401治疗的mCRPC患者的临床结局。目标2：评价接受90401治疗的mCRPC患者中SA从基线至疾病进展时间的连续变化是否具有OS的预后性。目的3：开发整合SA水平的mCRPC男性OS预后模型。该提案是检验SA是接受DP（标准治疗化疗）治疗的化疗初治mCRPC患者OS的预后和预测假设的首次分析。一个积极的发现将证实雄激素信号的重要性，即使在非常先进的疾病，正在接受一线化疗的设置。这项工作的意义是，SA可能是CRPC患者结局的一个不受重视的决定因素，在设计靶向或风险适应性治疗时应予以考虑。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SA水平可以预测治疗反应。由于90401是一项化疗研究，未使用雄激素合成抑制剂，因此验证这些结果表明，SA可预测CRPC的预后和结局，与治疗无关。