Adenoviral-mediated p53 gene transfer to non-small cell lung cancer through endobronchial injection

Objective: The objective was to determine the degree of toxicity and antitu mor activity following bronchoscopic injection of an adenoviral-mediated p5 3 gene (Adp53) into tumors causing airway obstruction. Dosing: This was a subset analysis of a phase I dose escalation trial. Setting: Patients were treated in the outpatient clinics at the University of Texas (MD Anderson Cancer Center, Houston, TX) and at Medical City Dalla s Hospital (US Oncology, Dallas, TX). Patients: Twelve patients (median age, 60 years) with advanced endobronchia l non-small cell lung cancer (NSCLC) (squamous cell carcinoma, six patients ; adenocarcinoma, six patients) were entered into trial. The median tumor a rea was 5 x 3.2 cm. All patient tumors contained a p53 gene mutation. Interventions: Adp53 (dose range, 1 x 10(6) to 1 x 10(11) plaque-forming un its) was administered by bronchoscopic intratumoral injection once every 28 days. Measurements and results: Toxicity attributed to the Adp53 vector was minim al. Six of the 12 patients had significant improvement in airway obstructio n, and 3 patients met the criteria for partial response. Conclusions: Direct bronchoscopic injection of Adp53 into endobronchial NSC LC is safe, with acceptable levels of toxicity. The initial clinical result s demonstrating relief of airway obstruction warrant further clinical inves tigation.