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Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.
- Source :
-
JNCI: Journal of the National Cancer Institute . 05/05/99, Vol. 91 Issue 9, p763-771. 9p. 1 Color Photograph, 2 Black and White Photographs, 1 Graph. - Publication Year :
- 1999
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CLINICAL trials
*ADENOVIRUSES
*SMALL cell lung cancer
*ANTISENSE DNA
Subjects
Details
- Language :
- English
- ISSN :
- 00278874
- Volume :
- 91
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- JNCI: Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 1837326
- Full Text :
- https://doi.org/10.1093/jnci/91.9.763