DEVELOPMENT OF POLY-L-GLUTAMIC ACID PACLITAXEL CONJUGATE

聚-L-谷氨酸紫杉醇缀合物的开发

• 批准号: 2860744
• 负责人: SIDNEY WALLACE
• 金额: $ 13.09万
• 依托单位: FEM CADET
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-15 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2860744
• 关键词: antineoplastics; athymic mouse; breast neoplasms; chemical conjugate; chemical synthesis; dogs; dosage; drug administration rate /duration; drug screening /evaluation; glutamates; laboratory mouse; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; ovary neoplasms; paclitaxel; pharmacokinetics

DESCRIPTION (Adapted from the application): Paclitaxel (Taxol) has shown significant activity in human cancers. However, clinical utility of Paclitaxel is limited by its insolubility in water and toxic side effects. We developed a water-soluble poly (L-glutamic acid)-Paclitaxel conjugate (PG-TXL) that has shown striking anti-tumor effects yet has low toxicity. A single intravenous injection of PG-TXL at its maximum tolerated dose resulted in complete disappearance of well-established breast and ovarian tumors in vivo. Based on its outstanding anti-tumor efficacy, PG-TXL is considered a promising anticancer agent for future clinical trials. The objective of the proposed studies is to investigate in detail the pre-clinical anti-tumor efficacy and relevant pharmacology/toxicology of PG-TXL and to address those aspects which will most likely influence the therapeutic efficacy and safety of PG-TXL in subsequent Phase I/II clinical trials. The specific aims are: 1. To define the dose-time sequence which would maximize the anti-tumor effects of PG-TXL. 2. To determine the pre-clinical toxicity of PG-TXL and define the starting dose for a clinical trial for breast and ovarian cancer patients. 3. To develop an analytical assay for determination of the time-dependent concentration changes of PG-TXL. The applicant's goal is expressed in the following sentence: "It is expected that PG-TXL will be less toxic and more effective than Taxol and that commercialization of PG-TXL in cancer patients will have significant impact on the management and treatment of breast cancer and ovarian cancer." PROPOSED COMMERCIAL APPLICATION: As a anti cancer agent.

描述（改编自应用程序）：紫杉醇（Taxol）已显示 在人类癌症中具有显著活性。然而，紫杉醇的临床用途 由于其在水中的不溶性和毒副作用而受到限制。我们开发了一个 水溶性聚（L-谷氨酸）-紫杉醇缀合物（PG-TXL），其具有 显示出显著的抗肿瘤作用且毒性低。 单次静脉注射PG-TXL的最大耐受剂量， 在完全消失的良好建立的乳腺和卵巢肿瘤， vivo.基于其突出的抗肿瘤疗效，PG-TXL被认为是一种 有前途的抗癌药物，用于未来的临床试验。 拟议研究的目的是详细调查 PG-TXL的临床前抗肿瘤疗效和相关药理学/毒理学 并解决那些最有可能影响治疗效果的方面， PG-TXL在后续I/II期临床试验中的有效性和安全性。 具体目标是： 1.确定最大化抗肿瘤效应的剂量-时间顺序 关于PG-TXL 2.确定PG-TXL的临床前毒性，并确定其起始剂量。 乳腺癌和卵巢癌患者的临床试验剂量。 3.开发一种分析方法，用于测定时间依赖性 PG-TXL浓度变化。 申请人的目标用下面的句子来表达：“预计 PG-TXL比紫杉醇毒性更小，更有效， PG-TXL在癌症患者中的商业化将对 乳腺癌和卵巢癌的管理和治疗。" 建议的商业应用：作为抗癌剂。