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（由申请人提供）：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）水平与总生存期（OS）的预后有关，较高的SA与生存期的改善有关系。已在两项 III 期随机研究中观察到，无论治疗组如何，但从未在雄激素合成抑制剂 (ASI)（如阿比特龙或酮康唑）不作为治疗的一部分的研究中观察到。来自 CALGB 90401 - NCI 资助的随机 III 期合作小组，比较了 CRPC 中的多西他赛加泼尼松 (DP) 与多西他赛/泼尼松加贝伐单抗 (DPB)。液相色谱串联质谱）技术，这些结果将与成熟患者的生存和结果数据相关。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改善的结果相关，包括生存，因为它反映了更有利的生物环境，其中肿瘤仍然部分依赖于雄激素：目的1：评估血清雄激素是否存在。在基线时使用超灵敏测定（雄烯二酮、DHEA-硫酸盐和睾酮）将可以对接受 CALGB 90401 治疗的 mCRPC 患者的临床结果进行预后和预测。 目标 2：评估接受 90401 治疗的 mCRPC 患者的 SA 从基线到疾病进展时间的连续变化是否对 OS 具有预后作用 AIM 3：开发整合 SA 水平的 mCRPC 男性 OS 预后模型。为了检验 SA 对接受 DP、标准护理化疗的初治 mCRPC 患者的预后和 OS 预测作用的假设，积极的发现将证实雄激素信号传导的重要性，即使在非常晚期的疾病中也是如此。这项工作的意义在于，SA 可能是 CRPC 患者预后的一个未被重视的决定因素，在设计靶向或风险适应疗法时应予以考虑。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 水平可能可以预测治疗反应，因为 90401 是一项化疗研究，没有使用雄激素合成抑制剂，验证这些结果表明 SA 是有效的。预后和无论治疗如何，均可预测 CRPC 的结果。