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 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.

SETTING

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).

PATIENTS

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.

INTERVENTIONS

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.

MEASUREMENTS AND RESULTS

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.

CONCLUSIONS

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.