CHEMOTHERAPEUTIC STUDIES IN SOLID TUMORS

实体瘤的化疗研究

• 批准号: 6299882
• 负责人: GEORGE J. BOSL
• 金额: $ 18.86万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2001-07-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299882
• 关键词: antineoplastic antibiotics; bladder neoplasm; bone marrow transplantation; breast neoplasms; cis platinum compound; clinical trials; colon neoplasms; combination cancer therapy; cyclophosphamide; drug screening /evaluation; germ cell neoplasms; head /neck neoplasm; human subject; human therapy evaluation; kidney neoplasms; lung neoplasms; methotrexate; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer nutrition therapy; neoplasm /cancer radiation therapy; neoplasm /cancer radionuclide therapy; polymerase chain reaction; prostate neoplasms; retinoids

In the revised Solid Tumor Project, we propose studies of new treatment for the non-hematologic malignancies. Each disease serves as a model system in which to test a concept which may have relevance to and subsequently be tested in other solid tumors with a similar biology. Five specific aims focus on new drugs, improved drug and radiation therapy delivery, and genetic mutations as prognostic factors. In Specific Aim 1, high-dose programs as proposed for patients with breast cancer and germ cell tumors. Since these two tumors are responsive to several drugs in different antineoplastic classes, they are excellent model systems in which to test the hypotheses of high-dose theory and new methods of stem cell reconstitution. In Specific Aim 2, we will determine the antitumor activity of combinations of an agent directed at a tumor-specific "target plus traditional cytotoxic drugs. Two agents will be studied initially. First, monoclonal antibody 225, which inhibits the binding of growth factor ligands to the epidermal growth factor receptor, inhibits proliferation in tumors which are dependent on this receptor for growth and is synergistic with cytotoxic drugs in vitro and in vivo. Second, the radiopharmaceutical 186Rhenium-HEDP targets tumor-induced new bone formation in bone metastases and will be studied in combination with chemotherapy in patients with prostate cancer. In Specific Aim 3, the antineoplastic activity of retinoids and other new drugs will be tested, both in traditional Phase II and in randomized trials. In Specific Aim 4, 3-dimensional treatment planning will be used to deliver radiation therapy to the tumor volume with greater precision and lesser local tissue toxicity in combination with chemotherapy. The initial goal is to improve local control of locally advanced non-small cell lung cancer, well-known to be associated with considerable mortality and morbidity from locally recurrent disease. In Specific Aim 5, the association between genetic alterations in TP53 and RB1 and response and survival will be studied in breast and head and neck cancer (in the case of TP53) and bladder cancer (for both TP53 and RB1). As we have demonstrated in the case of i(12p), the marker chromosome for germ cell tumors, genetic defects in tumors can be useful as diagnostic and prognostic tools in treatment selection. After optimization of treatment in Phase II trials, Phase III trials will be conducted and concepts applied in other relevant tumor systems.

在修订后的实体瘤项目中，我们提出了新治疗方法的研究 对于非血液系统恶性肿瘤。 每种疾病都是一个模型 系统，在其中测试可能与相关的概念 随后在具有相似生物学特性的其他实体瘤中进行测试。五 具体目标集中在新药、改进药物和放射治疗 分娩和基因突变作为预后因素。在具体目标 1 中， 针对乳腺癌和细菌患者建议的高剂量方案 细胞肿瘤。由于这两种肿瘤对多种药物有反应 不同的抗肿瘤类别，它们是优秀的模型系统 检验高剂量理论的假设和干细胞新方法 细胞重建。在具体目标2中，我们将确定抗肿瘤药物 针对肿瘤特异性“靶标”的药物组合的活性 加上传统的细胞毒药物。最初将研究两种药物。 一、单克隆抗体225，抑制生长结合 表皮生长因子受体的因子配体，抑制 肿瘤的增殖依赖于这种受体的生长 在体外和体内与细胞毒性药物具有协同作用。其次， 放射性药物 186Rhenium-HEDP 靶向肿瘤诱导的新骨 骨转移的形成，并将与 前列腺癌患者的化疗。在具体目标 3 中， 将测试类维生素A和其他新药的抗肿瘤活性， 在传统的 II 期试验和随机试验中。在具体目标 4 中， 3维治疗计划将用于实施放射治疗 以更高的精度和更少的局部组织来测量肿瘤体积 与化疗联合使用时的毒性。最初的目标是改善 局部晚期非小细胞肺癌的局部控制，众所周知 与当地相当大的死亡率和发病率有关 疾病反复发作。在具体目标 5 中，遗传之间的关联 TP53 和 RB1 的改变以及反应和生存将在 乳腺癌、头颈癌（TP53）和膀胱癌 （适用于 TP53 和 RB1）。正如我们在 i(12p) 的情况下所证明的那样， 生殖细胞肿瘤的标记染色体，肿瘤的遗传缺陷可以 可作为治疗选择中的诊断和预后工具。后 在II期试验中优化治疗，III期试验将 在其他相关肿瘤系统中进行的研究和概念应用。