Impact of Celecoxib and Inflammation on Survival in Stage III Colon Cancer

塞来昔布和炎症对 III 期结肠癌生存的影响

• 批准号: 8912878
• 负责人: CHARLES S FUCHS
• 金额: $ 79.18万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912878
• 关键词: 25-hydroxyvitamin D; Address; Adjuvant; Adjuvant Chemotherapy; Adjuvant Therapy; Area; Aspirin; Biological Markers; Blood; C-Peptide; Cancer Biology; Cancer and Leukemia Group B; Characteristics; Clinical; Clinical Trials; Colon Carcinoma; Colorectal Cancer; Complementary therapies; DNA; Data; Diet; Disease; Double-Blind Method; Enrollment; Epidemiology; Event; Exhibits; Exogenous Factors; Fluorouracil; Future; Genes; Genetic Polymorphism; Genomics; Grant; Growth Factor Overexpression; Habits; Inflammation; Insulin-Like Growth-Factor Binding Protein 1; Interleukin-6; Intervention; Knowledge; Life Style; Metabolism; Microsatellite Instability; Molecular; Obesity; Outcome; Oxidoreductase; PIK3CA gene; PPARG gene; Pathologic; Pathway interactions; Patients; Performance Status; Pharmaceutical Preparations; Placebo Control; Plasma; Play; Postoperative Period; Randomized; Randomized Clinical Trials; Research; Residual state; Resources; Risk; Role; Specimen; Staging; Toxic effect; Vascular Endothelial Growth Factors; Work; adiponectin; base; cancer recurrence; cancer therapy; cardiovascular risk factor; celecoxib; chemotherapy; clinical care; cohort; colon cancer patients; cyclooxygenase 2; density; energy balance; follow-up; improved; inflammatory marker; insight; mortality; mutant; outcome forecast; overexpression; prospective; public health relevance; targeted treatment; treatment strategy; tumor; tumor progression

DESCRIPTION (provided by applicant): Epidemiologic and scientific research indicates that diet, lifestyle, and other modifiable factors have a significant influence on the risk of developin colorectal cancer (CRC). However, the influence of these interventions on the survival of patients with established CRC remains poorly understood. While randomized clinical trials (RCTs) demonstrate a significant survival advantage for stage III colon cancer patients who receive adjuvant fluorouracil-based chemotherapy, 35-40% of stage III patients receiving current adjuvant chemotherapy still develop cancer recurrence. Patients often seek to understand what, if any diet, lifestyle or supplement will reduce their chances of cancer recurrence. Moreover, how diet and lifestyle influence prognosis may depend, in part, on specific patient characteristics as well as molecular alterations in the tumor. We propose to address these gaps in knowledge within a NCI-sponsored, large, double-blind, placebo- controlled RCT assessing the influence of celecoxib on survival in stage III colon cancer patients who are concurrently receiving standard adjuvant chemotherapy (CALGB 80702). Beyond directly addressing the role of COX inhibition, the trial provides a) two longitudinal prospective assessments of diet, medication usage, and lifestyle habits; b) tumor specimens to examine how exogenous factors interact with specific molecular alterations; c) prospectively collected blood and germline DNA; and d) extensive data on cancer recurrence, mortality, and treated-related toxicity. Since pathologic stage, performance status, post-operative therapy and follow-up are carefully defined in this trial, residual confounding by disease and treatment characteristics should be minimized. In this application, we propose to examine the influence celecoxib and inflammation (Aim 1), and relevant effect modifying pathways (Aim 2) on the risk of cancer recurrence, mortality, and treatment-related toxicity. Each aim extends current knowledge in these areas. Beyond the aforementioned hypotheses, this cohort will allow for the rapid examination of future hypotheses as they emerge. Ultimately, the proposed work seeks to improve our understanding of CRC biology, identify interventions that can improve patient survival, and, with the extensive clinical pathologic, genomic, and biomarker data available for analysis, inform clinicians how to maximally utilize these interventions to improve clinical care.

描述（由申请人提供）：流行病学和科学研究表明，饮食、生活方式和其他可改变的因素对患结直肠癌（CRC）的风险有显着影响。然而，这些干预措施对结直肠癌患者生存的影响仍知之甚少。虽然随机临床试验 (RCT) 证明接受基于氟尿嘧啶的辅助化疗的 III 期结肠癌患者具有显着的生存优势，但接受当前辅助化疗的 III 期患者仍有 35-40% 出现癌症复发。患者经常寻求了解哪些饮食、生活方式或补充剂可以降低癌症复发的机会（如果有的话）。此外，饮食和生活方式如何影响预后可能部分取决于特定的患者特征 以及肿瘤的分子改变。我们建议在 NCI 资助的大型双盲安慰剂对照随机对照试验中解决这些知识空白，该随机对照试验评估塞来昔布对同时接受标准辅助化疗的 III 期结肠癌患者生存的影响 (CALGB 80702)。除了直接探讨 COX 抑制的作用外，该试验还提供了 a) 对饮食、药物使用和生活习惯的两项纵向前瞻性评估； b) 肿瘤样本，用于检查外源因素如何与特定分子改变相互作用； c) 前瞻性收集的血液和种系 DNA； d) 关于癌症复发、死亡率和治疗相关毒性的广泛数据。由于本试验仔细定义了病理分期、体能状态、术后治疗和随访，因此应尽量减少疾病和治疗特征造成的残余混杂。在此应用中，我们建议检查塞来昔布和炎症（目标 1）的影响，以及相关效应修改途径（目标 2）对癌症复发、死亡率和治疗相关毒性风险的影响。每个目标都扩展了这些领域的现有知识。除了上述假设之外，该队列还将允许对未来出现的假设进行快速检验。最终，拟议的工作旨在提高我们对结直肠癌生物学的理解，确定可以提高患者生存率的干预措施，并利用可供分析的广泛临床病理、基因组和生物标志物数据，告知临床医生如何最大限度地利用这些干预措施来改善临床护理。