NEW DRUG DISCOVERY PROJECT

新药发现项目

• 批准号: 3853273
• 负责人: B S KRAMER
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3853273
• 关键词: 5 fluorouridine; antileukemic agent; antineoplastics; antitumor antibody; chronic leukemia; cis platinum compound; clinical trials; colorectal neoplasms; dipyridamole; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; etoposide; fluorouracil; human tissue; leucovorin; lung neoplasms; lymphocytic leukemia; methotrexate; monoclonal antibody; mycosis fungoides lymphoma; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer pharmacology; neoplasm /cancer radionuclide therapy; neoplastic cell; pyridine; tissue /cell culture; yttrium

The primary goal of this group is to identify new agents of potential clinical use in treating solid tumors. A major effort over the past 5 years has been the use of an in vitro assay which may be helpful as a preclinical screening model for antitumor agents. The model has been used to predict the clinical activity of 7 chemotherapeutic agents against 11 human colorectal carcinoma cell lines which have been developed in this branch. Using the model, we have shown that leucovorin enhances the in vitro cytotoxicity of the fluoropyridines versus our panel of colorectal cell lines. A study was also performed to detect possible synergy between etoposide and cisplatin in a panel of 8 human bronchogenic carcinoma cell lines. Extensive analysis revealed no in vitro synergy, a finding at variance with standard feeling. Schedule dependent drug interaction has been documented between methotrexate and 5-fluorouracil. Persantine has been shown to enhance the cytotoxicity of 10-EDAM in human lung cancer cell lines. Clinical trials are planned to explore this. At present, we are involved in several trials of new experimental therapeutic agents: a radiolabeled monoclonal antibody 90yttrium-T101) in mycosis fungoides and chronic lymphocytic leukemia; 4-ipomeanol in lung cancer. A phase I trial of hepsulfam has recently been completed, and maximally tolerated schedule identified as 360 mg/m2 i.v. every 5 weeks. Dose limiting toxicity was leukopenia.

该小组的主要目标是确定具有潜力的新代理人 临床用于治疗实体瘤。 过去5年的重大努力 多年来一直使用体外测定，这可能有助于 抗肿瘤药物的临床前筛选模型。 该模型已 用于预测7种化疗药物的临床活性 抗 11 种人类结直肠癌细胞系 在此分支中开发。 使用该模型，我们已经证明 亚叶酸增强氟吡啶的体外细胞毒性 与我们的结直肠细胞系组相比。 还进行了一项研究 检测依托泊苷和顺铂在一组药物中可能的协同作用 8 人支气管癌细胞系。 广泛分析揭示 没有体外协同作用，这一发现与标准感觉不一致。 已记录了时间表依赖性药物相互作用 甲氨蝶呤和5-氟尿嘧啶。 Persantine已被证明可以增强 10-EDAM 对人肺癌细胞系的细胞毒性。 临床 计划进行试验来探索这一点。 目前，我们正在参与多项新实验的尝试 治疗剂：放射性标记单克隆抗体 90yttrium-T101) 蕈样肉芽肿和慢性淋巴细胞白血病； 4-ipomeanol 在 肺癌。 Hepsulfam 的 I 期试验最近已完成， 最大耐受剂量为 360 mg/m2 i.v.每 5 个 几周。 剂量限制性毒性是白细胞减少。