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

基本信息

批准号：
8505928
负责人：
CHARLES S FUCHS
金额：
$ 63.33万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-19 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8505928
关键词：
25-hydroxyvitamin D Address Adjuvant Adjuvant Chemotherapy Adjuvant Therapy Area Aspirin Biological Markers Blood C-Peptide Cancer Biology Cancer Patient 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 Hydroxyprostaglandin Dehydrogenases Inflammation Insulin-Like Growth-Factor Binding Protein 1 Interleukin-6 Intervention Knowledge Life Style Metabolism Microsatellite Instability Molecular Obesity Outcome 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 cyclooxygenase 2 density energy balance follow-up improved inflammatory marker insight mortality mutant outcome forecast overexpression prospective public health relevance treatment strategy tumor tumor progression

项目摘要

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，生活方式和其他可修改因素对发生结直肠癌（CRC）的风险具有重大影响。但是，这些干预措施对已建立CRC患者存活的影响仍然鲜为人知。尽管随机临床试验（RCT）表现出接受基于氟尿嘧啶辅助化疗的III期结肠癌患者的显着生存优势，但接受当前辅助化疗的III期患者中有35-40％仍会发展出癌症的复发。患者经常寻求了解什么，如果任何饮食，生活方式或补充剂会减少癌症复发的机会。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中的分子改变。我们建议在NCI赞助的，大型，双盲，安慰剂控制的RCT中解决这些差距，以评估塞来昔布对同时接受标准辅助化学疗法（CALGB 80702）的III期结肠癌患者的生存影响。除了直接解决Cox抑制作用的作用外，该试验还提供了两项对饮食，用药和生活方式习惯的纵向前瞻性评估； b）肿瘤标本检查外源性因子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）有关癌症复发，死亡率和与治疗相关毒性的广泛数据。由于病理阶段，性能状况，术后疗法和随访在此试验中仔细定义，因此应最小化疾病和治疗特征的残留混淆。在此应用中，我们建议检查塞来氧化和炎症的影响（AIM 1），以及相关效果改变途径（AIM 2）对癌症复发，死亡率和与治疗相关毒性的风险。每个目标都扩展了这些领域的当前知识。除了上述假设之外，该队列还可以快速检查未来的假设。最终，拟议的工作旨在提高我们对CRC生物学的理解，确定可以改善患者生存的干预措施，以及可用于分析的广泛临床病理，基因组和生物标志物数据，请告知临床医生如何最大程度地利用这些干预措施来改善临床干预措施关心。