Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.

BACKGROUND: Preclinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA (Ad-p53). Therefore, in a phase I clinical trial, we administered Ad-p53 to 28 patients with non-small-cell lung cancer (NSCLC) whose cancers had progressed on conventional treatments. METHODS: Patients received up to six, monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection (23 patients) or bronchoscopy (five patients). The doses ranged from 10(6) plaque-forming units (PFU) to 10(11) PFU. RESULTS: Polymerase chain reaction (PCR) analysis showed the presence of adenovirus vector DNA in 18 (86%) of 21 patients with evaluable posttreatment biopsy specimens; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 (46%) of 26 patients. Apoptosis (programmed cell death) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling (TUNEL) staining in posttreatment biopsy specimens from 11 patients. Vector-related toxicity was minimal (National Cancer Institute's Common Toxicity Criteria: grade 3 = one patient; grade 4 = no patients) in 84 courses of treatment, despite repeated injections (up to six) in 23 patients. Therapeutic activity in 25 evaluable patients included partial responses in two patients (8%) and disease stabilization (range, 2-14 months) in 16 patients (64%); the remaining seven patients (28%) exhibited disease progression. CONCLUSIONS: Repeated intratumoral injections of Ad-p53 appear to be well tolerated, result in transgene expression of wild-type p53, and seem to mediate antitumor activity in a subset of patients with advanced NSCLC.

Baseline institutional compliance with NCCN guidelines: non-small-cell lung cancer.

To assess current physician practice patterns and whether they comply with guidelines published by the National Comprehensive Cancer Network (NCCN), we performed a retrospective review of 107 consecutive patients who underwent pulmonary resections for non-small-cell lung cancer at M. D. Anderson Cancer Center. Compliance with the guidelines was examined at four points in the patient's care: (1) preoperative work-up and evaluation, (2) operation performed and pathologic review, (3) postoperative adjuvant care, (4) routine follow-up and surveillance. Deviations from the guidelines were most marked in the preoperative evaluation phase. Excessive screening for metastases was performed in nearly 50% of the patients. Mediastinoscopy was appropriately utilized (according to the NCCN guidelines) in 93% of the patients, and appropriate anatomic resections and mediastinal nodal dissections were performed in 96% of the thoracotomies. Adjuvant care followed the NCCN recommendations in all patients. Excessive radiographic testing in asymptomatic patients was again seen in the postoperative surveillance program. Based on these findings, as well as the results of a previous evaluation of the cost-effectiveness of follow-up care in patients with resected lung cancers, we conclude that more widespread adherence to the radiographic recommendations in the NCCN guidelines would result in significant institutional and national health-care savings.