Oral mucositis risk & multicycle chemotherapy: Do multiple cycles multiply risk?

描述(申请人提供)：口腔粘膜炎(OM)是癌症治疗的一种痛苦和虚弱的后果，但其风险和结果在标准剂量的多周期化疗中描述得很少。这些信息的缺乏影响了临床决策和预防OM的临床试验设计。本研究的目的是：1)描述化疗期间临床意义上的OM与随后化疗周期中的风险之间的关系；2)建立后续周期风险的预测模型并评估该模型的预测价值；3)描述OM与临床和患者报告的结果之间的关系。将对177名结直肠癌、乳腺癌或非霍奇金淋巴瘤患者在1121个化疗周期中的OM风险和结果进行研究。化疗方案反映了目前世界各地治疗这些癌症的标准(FOLFOX、FOLFIRI、TAC、AC+T和CHOP)。数据将从现有的OM风险和结果数据库中获得，该数据库是在对癌症治疗引起的OM进行多中心、前瞻性、纵向研究期间创建的。这些目标在最初的研究中没有提出。然而，这些数据非常适合回答这个问题，因为患者报告的OM和结果是使用先前验证的工具在多个化疗周期中每天收集的。临床上有意义的OM的风险(受影响的患者或周期的百分比)将在每个周期被估计，然后使用多变量技术进行建模。随后的周期风险将根据之前的周期风险和严重性进行估计，并以类似的方式建模。将在多个化疗周期内检查结果和资源利用的模式。临床结果是体重减轻，阿片类药物需求，计划治疗延迟，剂量减少，以及发热性中性粒细胞减少或菌血症发作。患者报告的结果是对日常生活能力的干扰，止痛药的使用，以及疲劳和生活质量评分。医疗保健资源包括计划外门诊就诊、急诊室就诊和住院治疗。这项研究产生的信息将有助于识别实体肿瘤患者有临床意义的OM或其严重后果的风险，以便参与新预防药物的临床试验。 公共卫生相关性：这项研究的目标是确定在前一个化疗周期中经历过这种损伤的患者中，化疗导致的口腔和喉咙组织损伤的风险或严重程度是否更高。这些信息对于使用高成本预防性药物的临床决策和监测副作用的临床就诊频率至关重要；对于设计新疗法的临床试验也至关重要。

DESCRIPTION (provided by applicant): Oral mucositis (OM) is a painful and debilitating consequence of cancer therapy, but its risk and outcomes during standard dose, multi-cycle chemotherapy are poorly described. The lack of such information compromises clinical decision making and design of clinical trials addressing prevention of OM. The objectives of this study are to 1) characterize the relationship between clinically significant OM during chemotherapy and its risk during subsequent chemotherapy cycles, 2) develop a predictive model of subsequent cycle risk and to assess the model's predictive value, and 3) to describe associations between OM and clinical and patient-reported outcomes. OM risk and outcomes will be studied in 177 patients with colorectal or breast cancers or non-Hodgkins lymphoma during 1121 cycles of chemotherapy. The chemotherapy regimens reflect the current standard of care for these cancers, worldwide (FolFOX, FolFIri, TAC, AC+T, and CHOP). Data will be obtained from an existing database of OM risk and outcomes created during a multi-center, prospective, longitudinal study of cancer treatment-induced OM. These objectives were not posed during the original study. However, the data are ideally suited to answering this question because patient reported OM and outcomes were collected daily during multiple cycles of chemotherapy using previously validated tools. Risk of clinically significant OM (percentage of patients or cycles affected) will be estimated, per cycle, then modeled using multivariate techniques. Subsequent cycle risk will be estimated, conditioned on previous cycle risk and severity, and modeled in similar fashion. Patterns of outcomes and resource utilization will be examined over multiple chemotherapy cycles. The clinical outcomes are weight loss, requirement for opioids, delays in planned therapy, dose reductions, and episodes of febrile neutropenia or bacteremia. The patient- reported outcomes are interference with activities of daily living, pain medication usage, and fatigue and quality of life scores. The healthcare resources are unplanned outpatient office visits, emergency room visits, and hospitalizations. Information resulting from this study will be instrumental in identifying solid tumor patients at risk of clinically significant OM or its serious outcomes for participation in clinical trials of new preventive agents. PUBLIC HEALTH RELEVANCE: The goal of this study is to determine whether the risk or severity of chemotherapy-induced injury to the mouth and throat tissues is higher among patients who have experienced this injury during a previous cycle of chemotherapy. This information is critical to clinical decisions about use of high cost preventive agents and frequency of clinic visits for side effect monitoring; it is also critical to design of clinical trials of new therapeutics.