CHEMOTHERAPEUTIC STUDIES IN SOLID TUMORS

实体瘤的化疗研究

• 批准号: 6101348
• 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/6101348
• 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，我们提出了新的治疗方法 非血液系统恶性肿瘤 每一种疾病都是一种模式 测试一个概念的系统，该概念可能与 随后在具有类似生物学特性的其他实体瘤中进行测试。五 具体目标侧重于新药、改良药物和放射疗法 分娩和基因突变作为预后因素。具体目标1、 为乳腺癌和细菌感染患者提出的高剂量计划 细胞肿瘤由于这两种肿瘤对几种药物有反应， 不同的类，他们是优秀的模型系统， 以验证高剂量理论和干细胞新方法的假设 细胞重建在具体目标2中，我们将确定抗肿瘤 针对肿瘤特异性“靶标”的药剂组合的活性 加上传统的细胞毒性药物首先将研究两种药物。 首先，单克隆抗体225，它抑制生长的结合 表皮生长因子受体的因子配体，抑制 依赖于该受体生长的肿瘤增殖 和细胞毒药物在体内外具有协同作用。二是 放射性药物186铼-HEDP靶向肿瘤诱导的新骨 骨转移形成，并将与 前列腺癌的治疗方法具体目标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期和随机试验中。在具体目标4中， 3-三维治疗计划将用于提供放射治疗 以更高的精度和更少的局部组织 联合化疗的毒性。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， 复发性疾病在具体目标5中，遗传学之间的关联 TP 53和RB 1的改变以及反应和存活将在 乳腺癌和头颈癌（在TP 53的情况下）和膀胱癌 (for TP 53和RB 1）。正如我们在i（12 p）的情况下所证明的那样， 生殖细胞肿瘤的标记染色体，肿瘤中的遗传缺陷可以 在治疗选择中作为诊断和预后工具是有用的。后 II期试验中的治疗优化，III期试验将 在其他相关肿瘤系统中进行和应用的概念。