Adenoviral-Mediated p53 Gene Transfer to Non-small Cell Lung Cancer Through Endobronchial Injection

The objective was to determine the degree of toxicity and antitumor activity following bronchoscopic injection of anadenoviral-mediated p53 gene (Adp53) into tumors causing airwayobstruction. This was a subset analysis of aphase I dose escalation trial. Patients weretreated in the outpatient clinics at the University of Texas (MDAnderson Cancer Center, Houston, TX) and at Medical City DallasHospital (US Oncology, Dallas, TX). Twelvepatients (median age, 60 years) with advanced endobronchial non-smallcell lung cancer (NSCLC) (squamous cell carcinoma, six patients;adenocarcinoma, six patients) were entered into trial. The median tumorarea was 5 × 3.2 cm. All patient tumors contained a p53 genemutation. Adp53 (dose range,1 × 106 to 1 × 1011 plaque-forming units)was administered by bronchoscopic intratumoral injection once every 28days. Toxicity attributed tothe Adp53 vector was minimal. Six of the 12 patients had significantimprovement in airway obstruction, and 3 patients met the criteria forpartial response. Direct bronchoscopicinjection of Adp53 into endobronchial NSCLC is safe, with acceptablelevels of toxicity. The initial clinical results demonstrating reliefof airway obstruction warrant further clinicalinvestigation.