INNOVATIVE APPROACHES TO PATIENTS WITH ADENOCARCINOMA

腺癌患者的创新方法

• 批准号: 6499799
• 负责人: WALTER J CURRAN
• 金额: $ 29.68万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-07 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6499799
• 关键词: adenocarcinoma; antineoplastics; camptothecin; clinical research; clinical trial phase I; colorectal neoplasms; combination cancer therapy; combination chemotherapy; fluorouracil; human subject; human therapy evaluation; metastasis; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer surgery; oral administration; preoperative state

Until recently non-surgical therapeutic options for patients with cancer of the colon and rectum have been quite limited. The fluorinated pyrimidine 5-fluorouracil has been the basis of chemotherapeutic regimens used for metastatic or adjuvant therapy, in conjunction with pelvic radiation for patients with rectal cancer. Several new classes of chemotherapeutic agents and new routes of administration are now available in need of systematic testing. This project will execute four phase I/II trials for patients with advanced rectal cancer and five phase I/II trials for patients with metastatic or recurrent colorectal cancer. The unifying clinical hypothesis of these nine trials is that the introduction of oral analogues of fluorinated pyrimidine, camptothecin, and platinum agents to multi-modality regimens for rectal cancer and to salvage regimes for metastatic disease will improve clinical outcomes and the therapeutic ration for these patients. This project will test specific hypotheses, based on the basic science studies of investigators in Projects 2 and 3 regarding the relationship between tumor response and the status and degree of expression of genes implicated in the MMR-Pathway of tumor progression (Project 3) and the Aneuploid Pathway of tumor progression (Project 2). If these hypotheses are confirmed, the status of such genes as hMSH2, hMSH6, and Hmlh1 (MMR-pathway) and PLA2G2A (Aneuploid Pathway) in the sampled tumors of patients in these trials will be tested as eligibility criteria for subsequent clinical trials. These studies should provide a firm foundation for the integration of molecular genetic analysis as an important element of the therapeutic decision-making process for patients with cancer of the colon and rectum.

直到最近，结肠癌和直肠癌患者的非手术治疗选择还相当有限。氟化嘧啶 5-氟尿嘧啶一直是用于转移或辅助治疗的化疗方案的基础，与直肠癌患者的盆腔放疗结合使用。现在有几种新的化疗药物和新的给药途径需要系统测试。该项目将为晚期直肠癌患者开展四项I/II期试验，为转移性或复发性结直肠癌患者开展五项I/II期试验。这九项试验的统一临床假设是，将氟化嘧啶、喜树碱和铂类药物的口服类似物引入直肠癌的多模式治疗方案和转移性疾病的挽救方案将改善这些患者的临床结果和治疗比例。该项目将基于项目 2 和 3 中研究人员关于肿瘤反应与肿瘤进展的 MMR 途径（项目 3）和肿瘤进展的非整倍体途径（项目 2）中涉及的基因表达状态和程度之间关系的基础科学研究来测试具体假设。如果这些假设得到证实，这些试验中患者样本肿瘤中 hMSH2、hMSH6 和 Hmlh1（MMR 途径）和 PLA2G2A（非整倍体途径）等基因的状态将作为后续临床试验的资格标准进行测试。这些研究应该为分子遗传学分析的整合作为结肠癌和直肠癌患者治疗决策过程的重要组成部分提供坚实的基础。