INNOVATIVE APPROACHES TO PATIENTS WITH ADENOCARCINOMA

腺癌患者的创新方法

• 批准号: 6653309
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653309
• 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，针对结肠癌和直肠癌患者的非手术治疗方法一直有限。与直肠癌患者的骨盆辐射结合使用，氟化嘧啶5-氟尿嘧啶是用于转移或辅助治疗的化学治疗方案的基础。现在需要进行几种新的化学治疗剂和新的管理途径，需要系统的测试。该项目将针对患有晚期直肠癌患者的I/II期试验进行四项试验，并为转移性或复发性结直肠癌患者进行五项I/II期试验。这九项试验的统一临床假设是，氟化嘧啶，摄影剂和铂剂的口服类似物引入了直肠癌的多模态方案，并挽救了直肠癌的转移性疾病方案，将改善这些患者的临床疾病以及这些患者的治疗性评分。该项目将基于项目2和第3项目研究者的基础科学研究来检验特定的假设，涉及与肿瘤进展的MMR-Pathway（项目3）和肿瘤进展的非整倍型途径有关的基因的状态和表达程度（项目2）。如果这些假设得到证实，那么在这些试验中，在这些试验中采样肿瘤中HMSH2，HMSH6和HMLH1（MMR-PATHWAY）和PLA2G2A（ANEUPLOID途径）等基因的状态将作为随后的临床试验的有资格标准测试。这些研究应为将分子遗传分析整合为结肠和直肠癌患者的治疗决策过程的重要因素提供牢固的基础。