Eval of Efficacy/Mechs of Anti-inflammatory Intervention

口腔炎定义为口腔和口咽部粘膜炎症，以组织红斑、水肿和萎缩为特征，常发展为溃疡。口腔炎是一种生物学上复杂的、多因素的、与治疗相关的口腔疾病，许多肿瘤患者都经历过这种疾病，它经常导致一系列负面后遗症，包括口咽疼痛、严重的治疗改变或停止，以及生活质量下降。口腔炎的最佳治疗策略尚未确定。目前迫切需要在随机对照临床试验中研究口腔炎和相关急性口咽痛的发病机制并评估干预措施，使用有效和可靠的口腔炎评估工具，以推进癌症治疗相关口腔毒性的科学研究，并改善患者护理。因此，这项随机对照临床试验的目的是通过测试一种新型肿瘤坏死因子（TNF）融合蛋白依那西普(Enbrel？美国免疫学家，Immunex Corporation, Seattle， WA)研究了口腔炎的发病率和严重程度。这种融合蛋白与TNF特异性结合，阻止其与细胞受体的相互作用并改变炎症级联反应，可能为了解炎症在口炎中的作用提供线索。依那西普效应被定义为预防或改善口腔炎和急性口咽疼痛和/或改变组织介质水平。如果口腔炎主要是粘膜炎症反应的结果，那么我们假设这种口腔状况将对tnf - α的结合有反应。阐明炎症细胞信号在口腔炎中的作用和tnf - α的作用可能阐明与口腔炎发病机制和其他粘膜疾病相关的机制。

Stomatitis is defined as inflammation of the mucous membranes of the oral cavity and oropharynx characterized by tissue erythema, edema, and atrophy, often progressing to ulceration. Stomatitis is a biologically complex, multifactorial, treatment-related oral condition experienced by many oncology patients, which often leads to a cascade of negative sequelae including oropharyngeal pain, critical treatment alterations or cessation, and decreased quality of life. The optimal treatment strategies for stomatitis have not been established. There is a critical need to examine the pathogenesis of and to evaluate interventions for stomatitis and related acute oropharyngeal pain in the randomized controlled clinical trial setting using valid and reliable stomatitis assessment tools to both advance the science of cancer treatment-related oral toxicities and improve patient care. Therefore, the purpose of this randomized controlled clinical trial is to elucidate the role of inflammation in stomatitis by testing the effects of a novel tumor necrosis factor (TNF) fusion protein etanercept, (Enbrel?, Immunex Corporation, Seattle, WA) on the incidence and severity of stomatitis. The actions of this fusion protein, which binds specifically to TNF preventing its interaction with cellular receptors and altering the inflammatory cascade, may provide insight into the role of inflammation in stomatitis. An etanercept effect is defined as a prevention or amelioration of stomatitis and acute oropharyngeal pain and/or changes in levels of tissue mediators. If stomatitis is primarily a consequence of a mucosal inflammatory response, then we hypothesize that this oral condition will be responsive to binding of TNF-alpha. Elaboration of the role of inflammatory cell signalling associated with stomatitis and the effect of TNF-alpha may elucidate the mechanisms related to the pathogenesis of stomatitis and to other mucosal conditions. Patients who are scheduled to receive stomatogenic chemotherapy with autologous peripheral blood stem cell transplanation, ages 16 years or older, will be invited to participate in this study during a regularly scheduled pre-treatment visit in the National Institute of Dental and Craniofacial Research Dental Clinic, or through established recruitment strategies at a National Cancer Institute sponsored Community Clinical Oncology Program located at the Cancer Centers of the Carolinas, Greenville, SC. Written informed consent will be obtained from all participants. Patients will be randomized to receive either etanercept mouthwash or placebo, which will both be administered by protocol schedule. Stomatitis and oropharyngeal pain will be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course. TNF-alpha levels in buccal mucosa, analyzed by real time polymerase chain reaction techniques, and blood levels of pro-inflammatory cytokines, growth factors, and inflammatory mediators will also be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course. This study will begin to accrue subjects following the approval of the data and safety monitoring plan by the Data and Safety Monitoring Board, which convened in Augsut, 2005. The study transferred from the National Institute of Dental and Craniofacial Research to the National Institute of Nursing Research in 2004.