A Population Based Study of Ketorolac and Ovarian Cancer Survival

酮咯酸与卵巢癌生存的人群研究

• 批准号: 10457136
• 负责人: Linda S Cook
• 金额: $ 19.37万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-14 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457136
• 关键词: Accounting; Address; Adopted; Alberta province; Analgesics; Anesthesia procedures; British Columbia; Canada; Cancer Patient; Carcinoma; Cell Adhesion; Chemoresistance; Clear Cell; Clinical; Cohort Studies; Data; Diagnosis; Disease; Drug usage; Enterochromaffin Cells; Epithelial ovarian cancer; FDA approved; Goals; Greater sac of peritoneum; Guanosine Triphosphate Phosphohydrolases; Hand; Histology; Hospitals; Immunohistochemistry; Ketorolac; Knowledge; Leadership; Malignant Female Reproductive System Neoplasm; Malignant neoplasm of lung; Malignant neoplasm of ovary; Measures; Medical; Medical Records; Methods; Microscopic; Monomeric GTP-Binding Proteins; Mucinous; Non-Steroidal Anti-Inflammatory Agents; Operative Surgical Procedures; Ovarian; PTGS1 gene; PTGS2 gene; Pathology; Patients; Perioperative; Peritoneal; Pharmaceutical Preparations; Population Study; Prognosis; Prognostic Factor; Property; Ras Inhibitor; Recurrence; Recurrent disease; Reporting; Resources; Serous; Site; Stains; Standardization; Tissue Microarray; Translating; Woman; Work; cancer surgery; cancer survival; cancer therapy; clinical practice; cohort; comorbidity; data resource; experience; follow-up; improved; inhibitor/antagonist; malignant breast neoplasm; migration; mortality; neoplastic cell; novel; patient subsets; population based; protein expression; study population; tertiary prevention; tumor; tumor growth

Ovarian cancer is the most deadly gynecologic cancer in the U.S. and most patients still die of chemo-resistant, recurrent disease. We propose that a FDA-approved analgesic may also have anti-tumor properties that will reduce recurrent disease and improve survival if given during or closely following ovarian cancer surgery. Racemic R,S-ketorolac (Toradol® or a generic equivalent) is an strong non-steroidal anti-inflammatory drug (NSAID) used in conjunction with surgeries. We have been investigating ketorolac since 2008 and have compelling preliminary evidence to support the hypothesis that ketroloac can help reduce ovarian cancer mortality. Our work is supported further by reported recurrence and mortality reduction with surgery-associated ketorolac administration in breast and lung cancer patients. Combined, this compelling evidence suggests that ketorolac will confer an anti-tumor benefit; however, a reduction in ovarian cancer mortality with surgery- associated ketorolac (vs. none) has not been demonstrated. We propose to address this gap in our knowledge with a population-based cohort study of ovarian cancer cases. We hypothesize that ovarian cancer cases that are given ketorolac as an analgesic during ovarian cancer surgery will have better overall survival than those who do not receive ketorolac, after accounting for factors such as co-morbidities, stage of disease and received treatment. In addressing this hypothesis, we will use an existing cohort of population-based ovarian cancer cases from Alberta and British Columbia, Canada, who were diagnosed from 2002 to 2012 with mortality followed through 2020, providing between 8 and 18 years of follow-up. We will complete de novo medical record reviews to ascertain co-morbidities and all analgesics and anesthesia used during surgery for ovarian cancer. Existing data/resources that are already in hand includes: details of cancer treatments received, standardized pathology review to classify the tumors by contemporary criteria, and tissue micro-arrays (TMAs) (all histotypes). Using these TMAs, we will use immunohistochemical staining of markers that may define subsets of patients to address our mechanistic hypothesis. If ketorolac given in the surgical period makes a substantial improvement in survival, then the use of ketorolac would be an efficient and widely applicable method to improve survival within normal medical practice.

卵巢癌是美国最致命的妇科癌症，大多数患者仍然死于化疗耐药， 复发性疾病我们认为FDA批准的止痛药也可能具有抗肿瘤特性， 如果在卵巢癌手术期间或手术后立即给药，可减少疾病复发并提高生存率。 外消旋R，S-酮咯酸（Toradol®或仿制药）是一种强效非甾体抗炎药 （NSAID）与手术结合使用。自2008年以来，我们一直在研究酮咯酸， 令人信服的初步证据支持酮咯酸可以帮助减少卵巢癌的假设 mortality.我们的工作得到了手术相关的复发和死亡率降低的报告的进一步支持。 乳腺癌和肺癌患者的酮咯酸给药。综合起来，这一令人信服的证据表明， 酮咯酸将带来抗肿瘤益处;然而，手术降低卵巢癌死亡率- 尚未证实相关的酮咯酸（与无）。我们建议填补我们知识上的这一空白 对卵巢癌病例进行基于人群的队列研究。 我们假设在卵巢癌治疗期间给予酮咯酸作为镇痛剂的卵巢癌病例 在考虑了各种因素后，手术治疗的总生存率高于未接受酮咯酸治疗的患者。 如合并症、疾病分期和接受治疗。为了解决这个问题，我们将使用一个 来自加拿大阿尔伯塔和不列颠哥伦比亚省的现有基于人群的卵巢癌病例队列， 从2002年到2012年被诊断出死亡，直到2020年，提供8到18年的 随访我们将完成重新病历审查，以确定合并症和所有镇痛药， 卵巢癌手术中使用的麻醉剂。现有的数据/资源包括： 接受的癌症治疗的详细信息，标准化病理学审查，以按当代 标准和组织微阵列（TMA）（所有组织型）。利用这些TMA，我们将使用免疫组织化学 可以定义患者子集的标记物染色，以解决我们的机制假设。 如果在手术期间给予酮咯酸可以显著改善生存率， 将是在正常医疗实践中提高存活率的有效且广泛适用的方法。