Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer:: A phase I study of p53 gene therapy
Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer:: A phase I study of p53 gene therapy
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DOI：
10.1200/jco.2003.09.138
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发表时间：
2003-06-15
影响因子：
45.3
通讯作者：
Dinney, CP
中科院分区：
文献类型：
--
作者：
Pagliaro, LC;Keyhani, A;Dinney, CP
目的：我们研究了腺病毒介导的p53基因转移的可行性，安全性和生物学活性的患者与局部晚期bladder cancer.Patients和方法：可测量的，局部晚期膀胱移行细胞癌的患者谁是没有候选人的cytoplasmic是合格的。以28天为一个周期，在第1天和第4天以三个剂量水平（10（10）粒子至10（12）粒子）或连续4天或8天以单一剂量水平（10（12）粒子）膀胱内滴注INGN 201（Ad 5CMV-p53）。通过逆转录聚合酶链反应检测7例可评估患者中2例的膀胱活检组织中特异性转基因表达。11例可评估患者的免疫组化分析表明，膀胱上皮中p53、p21（waf 1/cip 1）或box蛋白水平无明显变化。门诊多疗程给药是可行的，耐受性良好。晚期浅表性膀胱癌的患者表现出肿瘤responsibility.Conclusion证据：膀胱灌注Ad 5CMV-p53是安全的，可行的，和生物活性时，在多剂量给药膀胱癌患者。这项研究的观察结果表明，这种治疗在浅表性移行细胞癌中具有抗肿瘤作用。需要提高基因转移的效率和基因表达水平以开发更有效的膀胱癌基因治疗。
Purpose: We investigated the feasibility, safety, and biologic activity of adenovirus-mediated p53 gene transfer in patients with locally advanced bladder cancer.Patients and Methods: Patients with measurable, locally advanced transitional-cell carcinoma of the bladder who were not candidates for cystectomy were eligible. On a 28-day cycle, intravesical instillations of INGN 201 (Ad5CMV-p53) were administered on days 1 and 4 at three dose levels (10(10) particles to 10(12) particles) or on either 4 or 8 consecutive days at a single dose level (10(12) particles).Results: Thirteen patients received a total of 22 courses without dose-limiting toxicity. Specific transgene expression was detected by reverse transcriptase polymerase chain reaction in bladder biopsy tissue from two of seven assessable patients. There were no changes in p53, p21(waf1/cip1), or box protein levels in bladder epithelium evident from immunohistochemical analysis of 11 assessable patients. Outpatient administration of multiple courses was feasible and well tolerated. A patient with advanced superficial bladder cancer showed evidence of tumor response.Conclusion: Intravesical instillation of Ad5CMV-p53 is safe, feasible, and biologically active when administered in multiple doses to patients with bladder cancer. Observations from this study indicate that this treatment has an antitumor effect in superficial transitional-cell carcinoma. improvements in the efficiency of gene transfer and the levels of gene expression are required to develop more effective gene therapy for bladder cancer.