P53 GENE THERAPY FOR LOCALLY ADVANCED BLADDER CANCER

描述：(申请人摘要)肌肉的标准治疗-- 浸润性膀胱癌是一种膀胱切除术。虽然通常是治愈的，但这是 肢解程序及其对生活质量的影响是 对许多患者来说是不可接受的。临床研究表明，患者 早期肌肉浸润性膀胱癌，其肿瘤携带突变 在P53、Rb或两者中，进展率较高且降低 单纯膀胱切除术后的存活率。正在进行的临床的目标 研究是为了优化化疗、手术和创新的使用 肌萎缩侧索硬化症患者的治疗方式 肿瘤可改善P53或Rb基因突变患者的预后 并在一个阶段的背景下开发膀胱癌的基因治疗 1复制缺陷型腺病毒载体Ad-p53的临床试验 局部膀胱癌患者的膀胱内灌注治疗 晚期膀胱癌。具体目标如下：1)行为 重组腺病毒p53膀胱内注射的1期临床试验 肌肉浸润性膀胱癌患者；2)表现为感染 腺病毒载体对肿瘤细胞的杀伤作用及p53基因的表达 膀胱内给药；3)研究P53的体内效应 基因转移对膀胱癌细胞凋亡的影响 P53基因转移对膀胱癌血管生成的调控作用vt.在.的基础上 完成第一阶段试验和相关实验室研究 描述，申请者将开发第二阶段的联合研究 早期肌肉浸润性膀胱癌的化疗联合Ad-P53基因治疗 器官保存的初步尝试失败的癌症患者。

DESCRIPTION: (Applicant's Abstract) The standard treatment for muscle- invasive bladder cancer is cystectomy. Though often curative, this is a mutilating procedure and its effects on quality of life are unacceptable to many patients. Clinical studies have shown that patients with early muscle-invasive bladder cancer whose tumors bear mutations of p53, RB, or both, have a higher rate of progression and decreased survival following cystectomy alone. An objective of ongoing clinical research is to optimize the use of chemotherapy, surgery, and novel therapeutic modalities in treatment of patients with muscle-invasive tumors to improve the prognosis of those that have p53 or RB mutations and to develop gene therapy for bladder cancer in the context of a Phase 1 clinical trial of the replication defective adenoviral vector Ad-p53, administered by intravesical instillation in patients with locally advanced bladder cancer. The specific aims are as follows: 1) conduct a Phase 1 clinical trial of intravesically administered Ad-p53 in patients with muscle-invasive bladder cancer; 2) demonstrate infection of tumor cells and expression of p53 gene by adenoviral vector through intravesical administration; 3) characterize the in vivo effect of p53 gene transfer on apoptosis in bladder cancer; 4) investigate effect of p53 gene transfer on regulation of angiogenesis in bladder cancer. Upon completion of the Phase 1 trial and correlative laboratory studies described, the applicant will develop a Phase II study of combined chemotherapy and Ad-p53 in patients with early muscle-invasive bladder cancer who have failed an initial attempt at organ preservation.