Managing metabolic disruption in pancreatic cancer to prevent weight loss and improve quality of life

管理胰腺癌的代谢紊乱以防止体重减轻并提高生活质量

• 批准号: 10722888
• 负责人: James H Flory
• 金额: $ 24.82万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722888
• 关键词: Antidiabetic Drugs; Blood Glucose; Body Weight; Body Weight Changes; Body Weight decreased; Body mass index; Cachexia; Cancer Etiology; Cessation of life; Clinical; Comparative Effectiveness Research; Continuous Glucose Monitor; Dangerousness; Data; Desire for food; Diabetes Mellitus; Diagnosis; Disadvantaged; Drug Exposure; Drug usage; Effectiveness; Electronic Health Record; Enrollment; Equilibrium; Genetic; Glipizide; Glucose; Histology; Hyperglycemia; Hypoglycemia; Inflammation; Insulin; Intervention; Knowledge; Laboratories; Maintenance; Malignant Neoplasms; Malignant neoplasm of pancreas; Malnutrition; Measurement; Measures; Metabolic; Metformin; Pancreatic Ductal Adenocarcinoma; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Phase III Clinical Trials; Placebos; Population; Probability; Production; Property; Publishing; Quality of life; Randomized; Recording of previous events; Research; Research Proposals; Resistance; Retrospective cohort study; Sample Size; Subgroup; Sulfonylurea Compounds; Supportive care; Survival Rate; Systemic Therapy; Testing; Time; Translating; United States; Weight Gain; anticancer treatment; arm; blood glucose regulation; clinical practice; comparative effectiveness; effectiveness outcome; electronic structure; experience; gastrointestinal; healthy weight; improved; improved outcome; mortality; neglect; prevent; randomized trial; repaired; safety assessment; safety outcomes; secondary analysis; side effect; tool; tumor progression; weight maintenance

PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is the fourth-leading cause of cancer death in the United States, with 60 000 cases diagnosed annually and five-year survival rate of only 10%. It is projected to become the second- leading cause of cancer-related mortality by 2030. PDAC is also associated with poor quality of life (QOL), including cachexia, in approximately 80% of patients. Cachexia is a contributing cause to 30% of deaths in PDAC and has no approved pharmacologic treatment. PDAC is also strongly associated with hyperglycemia. Half of patients have diabetes at the time of diagnosis and 80% experience hyperglycemia during treatment; the association is likely bi-directional, meaning that there is both evidence that diabetes causes PDAC and that PDAC causes diabetes. As a result, many patients with PDAC must use antidiabetic drugs such as metformin, sulfonylureas, or insulin. Hyperglycemia management during PDAC is an important aspect of supportive care with direct implications for QOL. Comparative effectiveness research on hyperglycemia management in PDAC is almost certain to improve supportive care by identifying which drugs best balance glucose control, side effects, and maintenance of healthy weight. This need for evidence in this specific population is especially pressing because the usual hierarchy of diabetes drugs may be inverted in PDAC patients. For example, prescribers deprecate sulfonylureas in routine diabetes practice in part because they promote weight gain, but that property could make them especially useful in patients with PDAC. Very little research has been done comparing sulfonylureas to metformin (the most widely used antidiabetic drug) or other alternatives as a supportive care intervention in PDAC. This proposal aims to close this evidence gap by, in Aim 1, conducting a retrospective cohort study testing the hypothesis that, compared to metformin, sulfonylureas are associated with better weight maintenance in patients with PDAC, and in Aim 2, enrolling 40 patients with hyperglycemia undergoing systemic treatment for PDAC in a trial assessing the safety of glipizide, a sulfonylurea, with respect to the key safety outcome of rate of hypoglycemia and the key effectiveness outcome of reducing blood glucose levels. This project will lay the groundwork for phase 3 clinical trials to determine whether choice of antidiabetic drug can improve QOL and even overall survival in patients with PDAC.

项目摘要 胰腺导管腺癌（PDAC）是美国癌症死亡的第四个主要原因， 每年诊断为60 000例病例，仅五年生存率仅为10％。预计将成为第二 到2030年，与癌症相关死亡率的主要原因。PDAC还与生活质量差（QOL）有关， 大约80％的患者在内，包括恶病质。病原体是PDAC死亡的30％的原因 并且没有批准的药理治疗。 PDAC也与高血糖密切相关。一半 患者在诊断时患有糖尿病，治疗期间80％患有高血糖；这 关联可能是双向的，这两个证据都表明糖尿病会导致PDAC，并且 PDAC引起糖尿病。结果，许多PDAC患者必须使用抗糖尿病药物，例如二甲双胍， 磺酰脲或胰岛素。 PDAC期间的高血糖管理是支持护理的重要方面 对QOL的直接影响。 PDAC中高血糖管理的比较有效性研究 几乎可以肯定可以通过确定哪些药物的最佳平衡葡萄糖控制，副作用， 和维持健康体重。在这个特定人群中，这种证据的需求特别紧迫 因为PDAC患者可能会反转糖尿病药物的通常层次结构。例如，处方者 在常规糖尿病中贬低磺酰氟尿的部分是因为它们会促进体重增加，但该特性 可以使它们在PDAC患者中特别有用。比较几乎没有研究 磺酰氟菌（二甲双胍（使用最广泛使用的抗糖尿病药物）或其他替代品作为支持护理 干预PDAC。该提议旨在通过AIM 1缩小这一证据差距进行回顾 队列研究检验了以下假设，即与二甲双胍相比，磺酰鲁鲁斯与重量更好 PDAC患者以及AIM 2的患者维护40例全身性高血糖患者 PDAC在一项试验中评估了Glipizide，sulfonylurea的安全性，相对于关键安全 低血糖率的结果和降低血糖水平的关键有效性结果。这 项目将为3阶段临床试验奠定基础，以确定选择抗糖尿病药物是否可以 改善PDAC患者的QOL甚至总体存活率。