Weill D, Mack M, Roth J, Swisher S, Proksch S, Merritt J, Nemunaitis J
Medical City Dallas Hospital, Dallas, TX, USA.
Chest. 2000 Oct;118(4):966-70. doi: 10.1378/chest.118.4.966.
The objective was to determine the degree of toxicity and antitumor activity following bronchoscopic injection of an adenoviral-mediated p53 gene (Adp53) into tumors causing airway obstruction. DOSING: This was a subset analysis of a phase I dose escalation trial.
Patients were treated in the outpatient clinics at the University of Texas (MD Anderson Cancer Center, Houston, TX) and at Medical City Dallas Hospital (US Oncology, Dallas, TX).
Twelve patients (median age, 60 years) with advanced endobronchial non-small cell lung cancer (NSCLC) (squamous cell carcinoma, six patients; adenocarcinoma, six patients) were entered into trial. The median tumor area was 5 x 3.2 cm. All patient tumors contained a p53 gene mutation.
Adp53 (dose range, 1 x 10(6) to 1 x 10(11) plaque-forming units) was administered by bronchoscopic intratumoral injection once every 28 days.
Toxicity attributed to the Adp53 vector was minimal. Six of the 12 patients had significant improvement in airway obstruction, and 3 patients met the criteria for partial response.
Direct bronchoscopic injection of Adp53 into endobronchial NSCLC is safe, with acceptable levels of toxicity. The initial clinical results demonstrating relief of airway obstruction warrant further clinical investigation.
确定经支气管镜向导致气道阻塞的肿瘤内注射腺病毒介导的p53基因（Adp53）后的毒性程度和抗肿瘤活性。给药：这是一项I期剂量递增试验的亚组分析。
患者在德克萨斯大学（休斯顿德克萨斯大学MD安德森癌症中心）和达拉斯医学城医院（达拉斯美国肿瘤学中心）的门诊接受治疗。
12例晚期支气管内非小细胞肺癌（NSCLC）患者（中位年龄60岁）入组试验，其中鳞状细胞癌6例，腺癌6例。肿瘤中位面积为5×3.2 cm。所有患者肿瘤均存在p53基因突变。
Adp53（剂量范围为1×10⁶至1×10¹¹空斑形成单位）通过支气管镜瘤内注射给药，每28天1次。
Adp53载体所致毒性极小。12例患者中有6例气道阻塞有显著改善，3例患者达到部分缓解标准。
经支气管镜直接向支气管内NSCLC注射Adp53是安全的，毒性水平可接受。初步临床结果显示气道阻塞得到缓解，值得进一步临床研究。
