Treatment Effects on Tumor 18F-Choline Metabolism in Advanced Prostate Cancer

晚期前列腺癌肿瘤 18F-胆碱代谢的治疗效果

• 批准号: 7672997
• 负责人: Sandi Alexander Kwee
• 金额: $ 38.32万
• 依托单位: QUEEN'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672997
• 关键词: Affect; Androgen Antagonists; Androgens; Antiandrogen Therapy; Cessation of life; Characteristics; Choline; Clinical; Clinical Trials; Derivation procedure; Disease; Disease Progression; Fluorine; Goals; Hormones; Image; Imaging Techniques; Individual; Knowledge; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of prostate; Measurable; Measurement; Measures; Metabolism; Metastatic Prostate Cancer; Metastatic to; Methods; Monitor; Neoplasm Metastasis; New Agents; Outcome; Pain; Patient Care; Patients; Pharmaceutical Preparations; Phase II Clinical Trials; Pilot Projects; Positron-Emission Tomography; Prostate-Specific Antigen; Refractory; Research; Speed; Surrogate Markers; Techniques; Therapeutic; Time; Tracer; United States; Withdrawal; X-Ray Computed Tomography; active method; androgen independent prostate cancer; base; chemotherapeutic agent; chemotherapy; clinical practice; design; docetaxel; drug development; drug withdrawal; effective therapy; hormone refractory prostate cancer; hormone resistance; imaging modality; in vivo; male; meetings; molecular imaging; novel; outcome forecast; public health relevance; response; surrogacy; time interval; treatment effect; treatment response; tumor; uptake

DESCRIPTION (provided by applicant): The prognosis for patients with metastatic hormone refractory prostate cancer (HRPC) is poor with a median survival of 16 to 18 months despite modern chemotherapy. Docetaxel, alone or in combination with other chemotherapeutic agents, is currently the most active treatment available for HRPC. However, because docetaxel confers only a modest survival benefit, there is a need for more effective drugs. Unfortunately, difficulties in imaging and quantifying disease progression in HRPC have continued to hinder drug development and clinical trials. Molecular imaging techniques such as positron emission tomography/ computed tomography (PET/CT) may contribute novel ways of measuring tumor responses to therapy for both clinical trials and clinical practice. Fluorine-18 fluorocholine (18F-choline) is an investigational PET tracer that has shown considerable promise for imaging hormone-refractory and hormone-naive prostate cancer. In pilot studies, docetaxel has been shown to modulate the uptake of 18F-choline by metastatic tumors. Our goal is to determine whether measurement of these treatment-associated changes in tumor 18F-choline uptake can be used to gauge therapeutic response in HRPC. This R21 proposal to study the short-term effects of docetaxel and androgen hormone manipulation on 18F-choline metabolism will resolve methodological issues relevant to the design of a longitudinal study evaluating 18F-choline PET/CT-based measures as surrogate markers for survival and pain outcomes in patients with HRPC receiving chemotherapy. Our aims are: 1) examine the relationship between changes in tumor 18F-choline uptake and changes in prostate specific antigen level in response to docetaxel treatment of HRPC, 2) examine the time course by which changes in tumor 18F-choline uptake occur during docetaxel chemotherapy, and 3) examine the effects of anti-androgen drug withdrawal on tumor 18F-choline uptake in prostate cancer that is becoming hormone-insensitive. The feasibility of a longitudinal study to evaluate 18F-choline PET/CT as a tumor response measure in HRPC will be based on meeting these aims. Pursuit of these aims may also result in a technique to aid in treating and investigating docetaxel and hormone resistance in HRPC. PUBLIC HEALTH RELEVANCE: Despite modern advancements in chemotherapy, the prognosis for patients with metastatic prostate cancer is poor and virtually all deaths from prostate cancer are due to metastatic disease. Difficulties in imaging and quantifying the disease continue to create barriers for new drug development and clinical trials. We propose to investigate a method of molecular imaging that in concert with conventional imaging could enhance the ability to detect, monitor, and predict the effects of chemotherapy on metastatic tumors, to the point that effective treatments can be customized based on the tumor characteristics of each individual patient.

描述（由申请人提供）：转移性激素难治性前列腺癌（HRPC）患者的预后很差，尽管进行了现代化疗，中位生存期为16至18个月。多西他赛，单独或与其他化疗药物联合，是目前最积极的治疗HRPC。然而，由于多西他赛仅提供适度的生存益处，因此需要更有效的药物。不幸的是，成像和量化HRPC疾病进展的困难继续阻碍药物开发和临床试验。分子成像技术，如正电子发射断层扫描/计算机断层扫描（PET/CT）可能有助于测量肿瘤对临床试验和临床实践的治疗反应的新方法。氟-18氟胆碱（18F-胆碱）是一种研究PET示踪剂，已显示出相当大的前景成像难治性和未经化疗的前列腺癌。初步研究显示，多西他赛可调节转移性肿瘤对18F-胆碱的摄取。我们的目标是确定这些治疗相关的肿瘤18F-胆碱摄取变化的测量是否可以用来衡量HRPC的治疗反应。这项研究多西他赛和雄激素控制对18 F-胆碱代谢的短期影响的R21提案将解决与纵向研究设计相关的方法学问题，该纵向研究评价了基于18 F-胆碱PET/CT的指标作为接受化疗的HRPC患者生存和疼痛结局的替代标志物。我们的目标是：1）检查肿瘤18 F-胆碱摄取的变化与响应多西他赛治疗HRPC的前列腺特异性抗原水平变化之间的关系，2）检查多西他赛化疗期间肿瘤18 F-胆碱摄取发生变化的时间过程，3）检查抗雄激素药物停药对前列腺癌中肿瘤18 F-胆碱摄取的影响，该前列腺癌变得不敏感。在HRPC中评价18F-胆碱PET/CT作为肿瘤缓解指标的纵向研究的可行性将基于满足这些目标。追求这些目标也可能导致一种技术，以帮助治疗和研究多西他赛和激素抵抗的HRPC。 公共卫生相关性：尽管现代化疗取得了进步，但转移性前列腺癌患者的预后很差，几乎所有前列腺癌死亡都是由于转移性疾病。成像和量化疾病的困难继续为新药开发和临床试验创造障碍。我们建议研究一种分子成像方法，该方法与常规成像相结合，可以提高检测，监测和预测化疗对转移性肿瘤的影响的能力，从而可以根据每个患者的肿瘤特征定制有效的治疗方法。