Antioxidant supplements, genetics and chemotherapy outcomes

抗氧化剂补充剂、遗传学和化疗结果

• 批准号: 7284790
• 负责人: Christine B. Ambrosone
• 金额: $ 59.9万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-06 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7284790
• 关键词: Address; Adjuvant Chemotherapy; Adjuvant Study; Adriamycin PFS; American; Ancillary Study; Antioxidants; Apoptosis; Blood specimen; Cancer Patient; Caring; Cell Death; Cells; Clinical Data; Clinical Research; Clinical Trials; Cohort Effect; Cyclophosphamide; DNA; Data; Databases; Diagnostic Neoplasm Staging; Diet; Disease; Disease-Free Survival; Dose; Enrollment; Future; GSTP1 gene; Generations; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Guidelines; Institutes; Lead; Life Style; Modification; Negative Axillary Lymph Node; Normal Cell; Numbers; Observational Study; Outcome; Oxidative Stress; Paclitaxel; Parents; Patients; Pharmaceutical Preparations; Phase; Physical activity; Physicians; Population Study; Positive Lymph Node; Proteins; Randomized; Reactive Oxygen Species; Recommendation; Reporting; Research; Research Design; Research Personnel; Risk; Role; Southwest Oncology Group; Specimen; Surveys; Telephone Interviews; Testing; Therapeutic; Time; Today; Toxic effect; Treatment Efficacy; Treatment Protocols; Treatment outcome; Tumor stage; Upper arm; Variant; Vitamins; Woman; anticancer research; base; cancer cell; cancer recurrence; cell injury; cell killing; chemotherapeutic agent; chemotherapy; cytotoxic; dietary antioxidant; glutathione S-transferase pi; malignant breast neoplasm; neoplastic cell; programs; research study; size; sound; statistical center; treatment trial; tumor

DESCRIPTION (provided by applicant): Cancer patients report widespread use of antioxidant supplements during chemotherapy, despite the recommendations by the American Institute for Cancer Research and others that supplements not be used during treatment. These guidelines are based upon the fact that numerous chemotherapeutic agents, including those used to treat breast cancer, exert their cytotoxic effects by generation of reactive oxygen species (ROS), which cause massive damage to DNA and proteins and trigger apoptosis, resulting in tumor and normal cell death. Thus, there is the concern that antioxidants may block the ROS-generated effects of therapy on tumor cells. There are no data based on sound epidemiological or clinical studies to support this hypothesis, however. In fact, some experimental studies have shown that antioxidants may potentiate the effects of chemotherapeutic drugs, while also lessening treatment-related toxicities. We will investigate the question of whether or not use of antioxidant supplements during adjuvant chemotherapy has any impact on toxicities and disease-free, as well as overall, survival, and also evaluate the role of polymorphisms in genes related to oxidative stress in relation to treatment outcomes in the context of a newly activated Southwest Oncology Group (SWOG) clinical trial. In the ongoing Phase III Intergroup parent study chaired by SWOG, S0221, patients are randomized onto one of four arms that test different doses/intensities/intervals of cyclophosphamide, adriamycin, and paclitaxel. Blood specimens are being collected and banked. All patients upon enrollment in the treatment trial will be asked to be contacted for participation in this ancillary study. Telephone interviews will be conducted at the initiation of therapy, and at completion of treatment, regarding use of antioxidant supplements and other lifestyle factors. DNA will be genotyped for polymorphisms in a number of oxidative stress-related genes. Data will be analyzed at the SWOG Statistical Center, and supplement use and genetic variability will be evaluated in relation to toxicities, as well as to disease-free and overall survival. We will also explore the potential modification of antioxidant use on treatment outcomes by genetic variability. Because of the expected large size of this study, and the homogeneity of the study population and treatments given, the proposed study will have the capabilities to answer an extremely important question in the care of cancer patients today, and provide data that may lead to reduced treatment toxicities and increased disease-free survival.

描述（由申请人提供）：癌症患者报告了化学疗法期间对抗氧化剂补充剂的广泛使用，尽管美国癌症研究所和其他在治疗过程中不使用补充剂的建议提出了建议。这些指南基于以下事实：许多化学治疗剂，包括用于治疗乳腺癌的化学剂，通过产生活性氧（ROS）发挥其细胞毒性作用，它们会对DNA和蛋白质造成巨大损害，并触发凋亡，导致肿瘤和正常细胞死亡。因此，人们担心抗氧化剂可能会阻止治疗对肿瘤细胞的ROS产生作用。但是，没有基于声音流行病学或临床研究的数据来支持这一假设。实际上，一些实验研究表明，抗氧化剂可能会增强化学治疗药物的作用，同时减少与治疗相关的毒性。我们将调查一个问题：辅助化疗期间是否使用抗氧化剂补充剂会对毒性和无疾病以及总体生存产生任何影响，并评估多态性在与氧化应激相关的基因中的作用在与新型激活的Southwest Oncologation Compotic Clotic Group（Swog Group）的背景下（Swog swog swog swog swog）相关的基因中。在正在进行的III期群体间父母研究中，SWOG主持了S0221，将患者随机分配到四个臂之一，该臂测试了环磷酰胺，adriamycin和paclitaxel的不同剂量/强度/间隔。血液标本正在收集和储存。参加治疗试验的所有患者都将被要求与这项辅助研究联系。有关使用抗氧化剂补充剂和其他生活方式因素，将在开始治疗和完成治疗时进行电话访谈。在许多氧化应激相关基因中，将对DNA进行基因分型。数据将在SWOG统计中心进行分析，并将评估与毒性以及无疾病和整体生存有关的补充使用和遗传变异性。我们还将通过遗传变异探索对治疗结果的抗氧化剂使用的潜在修饰。由于这项研究的预期大小以及研究人群和治疗的同质性，拟议的研究将具有回答当今癌症患者护理的极为重要问题的能力，并提供可能导致治疗毒性降低和无疾病生存的数据。