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: 8737807
• 负责人: CHARLES S FUCHS
• 金额: $ 72.07万
• 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 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8737807
• 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

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结直肠癌（CRC）的发生风险有显著影响。然而，这些干预措施对结直肠癌患者生存的影响仍然知之甚少。虽然随机临床试验（rct）显示，接受氟尿嘧啶辅助化疗的III期结肠癌患者具有显著的生存优势，但接受当前辅助化疗的III期患者中仍有35-40%发生癌症复发。患者经常寻求了解，如果有任何饮食、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患者的具体特征