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大原因， 每年确诊6万例，5年生存率仅为10%。它预计将成为第二个- 到2030年成为癌症相关死亡的主要原因。PDAC还与生活质量（QOL）差有关， 包括恶病质，大约80%的患者。恶病质是导致PDAC中30%死亡的原因 并且没有批准的药物治疗。PDAC也与高血糖症密切相关。半年 患者在诊断时患有糖尿病，80%的患者在治疗期间出现高血糖; 这种关联可能是双向的，这意味着既有证据表明糖尿病导致PDAC， PDAC导致糖尿病。因此，许多PDAC患者必须使用抗糖尿病药物，如二甲双胍， 磺酰脲类或胰岛素。PDAC期间的高血压管理是支持性治疗的一个重要方面 对生活质量有直接影响PDAC高血糖管理的效果比较研究 通过确定哪些药物最能平衡血糖控制，副作用， 保持健康的体重。在这一特定人群中，对证据的需求尤为迫切 因为糖尿病药物的通常等级在PDAC患者中可能颠倒。例如，开处方者 在常规糖尿病治疗中不推荐使用磺酰脲类药物，部分原因是它们会促进体重增加， 可以使它们在PDAC患者中特别有用。很少有研究比较 磺脲类药物替代二甲双胍（最广泛使用的降糖药物）或其他替代药物作为支持性治疗 在PDAC的干预。该提案旨在通过在目标1中进行回顾性研究， 一项队列研究，检验与二甲双胍相比，磺脲类药物与更好的体重相关的假设 在目标2中，招募了40例高血糖患者， 在一项评估磺酰脲类药物格列吡嗪在关键安全性方面的安全性试验中， 低血糖发生率结局和降低血糖水平的关键有效性结局。这 该项目将为3期临床试验奠定基础，以确定抗糖尿病药物的选择是否可以 改善PDAC患者的生活质量甚至总生存率。