Effects of Antioxidant Supplementation during Breast Cancer Adjuvant Therapy

乳腺癌辅助治疗期间补充抗氧化剂的作用

基本信息

批准号：
8312329
负责人：
Heather Greenlee
金额：
$ 15.28万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-21 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8312329
关键词：
Academic Medical Centers Adjuvant Adjuvant Therapy Adverse effects Adverse event Affect Antioxidants Area Award Biological Markers Biostatistical Methods Brain natriuretic peptide Breast Breast Cancer Treatment California Cancer Control Cancer Patient Cancer Survivor Cardiac Cardiotoxicity Chemotherapy-Oncologic Procedure Clinical Clinical Trials Clinical Trials Design Coenzyme Q10 Cohort Studies Common Terminology Criteria for Adverse Events Complementary and alternative medicine Creatinine Data Diagnosis Disease-Free Survival Doctor of Philosophy Doxorubicin Drug Kinetics Echocardiography Enrollment F2-Isoprostanes Fatigue Funding Gene-Modified Genes Genetic Crossing Over Genetic Polymorphism Goals Individual Intake Intervention Late Effects Left Lipids Long-Term Effects Malignant Neoplasms Malondialdehyde Measures Mentored Patient-Oriented Research Career Development Award Mentorship Metabolism Mitochondria Molecular Epidemiology Multivitamin Observational Study Outcome Outcome Study Oxidative Stress Oxidative Stress Pathway Participant Pathway interactions Patients Phase Phase III Clinical Trials Phosphotransferases Placebo Control Placebos Plasma Prevention Principal Investigator Radiation Radiation therapy Randomized Reactive Oxygen Species Recurrence Reporting Research Personnel Risk Safety Smoking History Staging Supplementation Symptoms Time Toxic effect Training Treatment Efficacy Troponin I Ventricular Woman arm cancer prevention cancer radiation therapy cancer recurrence cancer therapy chemotherapy clinical practice design dietary antioxidant dietary supplements effective therapy fruits and vegetables hormone therapy interest investigator training malignant breast neoplasm member oncology prevent primary outcome prospective randomized placebo controlled trial secondary outcome treatment effect urinary

项目摘要

DESCRIPTION (provided by applicant): The goal of this K23 Mentored Patient-Oriented Research Career Development Award is to develop Heather Greenlee, ND, PhD's expertise in the safety and efficacy of antioxidant supplement use during breast cancer adjuvant therapy. The use of antioxidant supplements during cancer radiation therapy and chemotherapy is controversial because the short- and long-term effects of this use are largely unknown. For example, coenzyme Q10 (C0QIO), a lipid soluble antioxidant, has been hypothesized to decrease doxorubicin-induced cardiotoxicity. However it is unknown if using an antioxidant supplement such as CoQ 10 during doxorubicin treatment would decrease doxorubicin's long-term treatment efficacy. Despite this controversy, an estimated 45-80% of breast cancer patients use antioxidant supplements during their treatment. Well designed observational studies and clinical trials are needed to elucidate the effects of these agents. In this proposed award, I will receive focused mentorship and training from established investigators at Columbia University Medical Center in the areas of oncology clinical trials (Dawn Hershman, MD, MS), pathways of oxidative stress (Regina Santella, PhD), and cancer prevention and control (Alfred Neugut, MD, PhD). I will complete coursework and training in molecular epidemiology, biostatistical methods, clinical trial design, and cancer prevention and control. Three complementary studies are proposed to study the early and late effects of antioxidant supplement use during adjuvant treatment for breast cancer. Study one is a phase I randomized, placebo-controlled, pharmacokinetic study on the effect of C0QIO on doxorubicin metabolism during breast cancer treatment. Study Two is a phase Mb randomized, placebo-controlled trial on the effect of C0QIO preventing doxorubicin-induced cardiotoxicity during breast cancer treatment. Study Three is a nested cohort study within the Pathways Study examining the effects of antioxidant supplement use during breast cancer chemotherapy, radiation therapy, and hormonal therapy on breast cancer recurrence and survival. The Pathways Study is an NCI-funded prospective cohort study of breast cancer patients diagnosed within Kaiser Permanente Northern California (n=3,000; PI: Lawrence Kushi, ScD). At the completion of this proposed award, I will be an independent researcher and expert in the use of clinical trials and observational studies to examine the short- and long-term effects of antioxidant supplement use during breast cancer treatment, and will be fully prepared to pursue NCI R01 funding. RELEVANCE: A large proportion of cancer patients use antioxidant supplements during cancer treatment. However, the eariy and late effects of this use are largely unknown, and may be harmful. Well trained investigators are needed to conduct observational studies and clinical trials in this area to elucidate the short- and long-term effects of these agents.

描述（由申请人提供）：这项K23指导的以患者为导向的研究职业发展奖的目标是开发ND Heather Greenlee，博士在乳腺癌辅助治疗期间在抗氧化剂补充剂使用方面的安全性和有效性方面的专业知识。在癌症放射治疗和化学疗法期间使用抗氧化剂补充剂是有争议的，因为这种使用的短期和长期影响在很大程度上是未知的。例如，辅酶Q10（C0QIO）是一种脂溶性抗氧化剂，已被认为可以降低阿霉素诱导的心脏毒性。但是，未知是否在阿霉素治疗期间使用抗氧化剂补充剂（例如COQ 10）会降低阿霉素的长期治疗功效。尽管存在这一争议，但估计有45-80％的乳腺癌患者在治疗过程中使用抗氧化剂补充剂。需要精心设计的观察性研究和临床试验来阐明这些药物的影响。在这项拟议的奖项中，我将在哥伦比亚大学医学中心的既定研究人员中获得肿瘤学临床试验领域（Dawn Hershman，MD，MS），氧化应激途径（Regina Santella，Phd）和癌症预防和对照（AlfredNeugut，MD，PHD）的重点指导和培训。我将完成分子流行病学，生物统计学方法，临床试验设计以及癌症预防和对照方面的课程和培训。提出了三项互补研究，以研究乳腺癌辅助治疗期间抗氧化剂补充剂使用的早期和晚期作用。研究第一是I期关于C0QIO对乳腺癌治疗过程中C0QIO对阿霉素代谢的影响的随机，安慰剂对照的药代动力学研究。研究二是一项有关C0QIO在乳腺癌治疗过程中阻止阿霉素诱导的心脏毒性的效果的MB期随机，安慰剂对照试验。研究三是一项在途径研究中的嵌套队列研究，研究了乳腺癌化学疗法，放射治疗和荷尔蒙治疗对乳腺癌复发和生存期间抗氧化剂补充剂的影响。途径研究是一项由NCI资助的前瞻性队列研究，对北加州Kaiser Permanente内部诊断出的乳腺癌患者（n = 3,000; PI：Lawrence Kushi，SCD）。该提议奖励完成后，我将成为使用临床试验和观察性研究的独立研究人员和专家，以检查乳腺癌治疗期间抗氧化剂补充剂的短期和长期影响，并将充分准备从事NCI R01资金。相关性：很大一部分癌症患者在癌症治疗过程中使用抗氧化剂补充剂。但是，这种使用的耳朵和后期作用在很大程度上是未知的，可能是有害的。需要经过良好训练的研究人员在该领域进行观察性研究和临床试验，以阐明这些药物的短期和长期影响。