Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma
Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma
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DOI：
10.1200/jco.1998.16.6.2221
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发表时间：
1998-06-01
影响因子：
45.3
通讯作者：
Goepfert, H
中科院分区：
文献类型：
--
作者：
Clayman, GL;El-Naggar, AK;Goepfert, H
目的：头颈部鳞状细胞癌(HNSCC)的标准治疗方法通常会导致严重的并发症，并且在过去的30年里并没有显著提高生存率。临床前研究表明，野生型p53基因的腺病毒载体可以减少小鼠异种移植模型中的肿瘤生长。我们的目的是确认腺病毒(Ad)-P53在晚期HNSCC中的安全性和治疗潜力。患者和方法：无法治愈的复发局部或区域转移的HNSCC患者接受了多次瘤内注射Ad-P53，包括肿瘤切除或不切除。监测患者的不良事件和抗腺病毒抗体，监测肿瘤的反应和P53的表达，并分析体液中的Ad-P53。结果：33例患者的肿瘤注射剂量高达1×10(11)空斑形成单位(PFU)，未发现剂量限制性毒性或严重不良事件。在肿瘤活检组织中检测到P53的表达，尽管在注射Ad-P53后有抗体反应。17例不能切除的肿瘤患者可评估临床疗效：2例肿瘤客观消退大于50%，6例患者病情稳定达3.5个月，9例患者病情进展。一名可切除的患者被认为是完全病理反应。结论：肿瘤内注射Ad-P53是安全的。目的在几例患者中检测到抗肿瘤活性，体液中感染性的Ad-P53无症状，提示全身或局部治疗是可以耐受的。这些结果表明，Ad-P53作为治疗HNSCC的药物值得进一步研究。(C)1998年由美国临床肿瘤学会主办。
Purpose: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. Patients andMethods: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumorol injections of Ad-p53, either with or without tumor resection. patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53,Results: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu), No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 war detected in blood and urine in a dose-dependent fashion, and in sputum.Conclusion: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients; The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 ar a therapeutic agent for patients with HNSCC. (C) 1998 by American Society of Clinical Oncology.