Title
Phase I study of adenovirus p53 administered by bronchoalveolar lavage in patients with bronchioloalveolar cell lung carcinoma: ECOG 6597
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Physiology
Publication Date
2008-09-02
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
PURPOSE: This pilot phase I trial evaluated the safety and maximum-tolerated dose of p53 gene transfer using an adenovirus vector (Ad-p53) delivered via bronchoalveolar lavage (BAL) to patients with bronchioloalveolar lung carcinoma (BAC).
PATIENTS AND METHODS: Patients were initially administered two treatments of Ad-p53 to a single involved lobe, beginning at 2 x 10(9) viral particles (vp) per dose and escalated to a maximum of 2 x 10(12) vp. If a clinical benefit was seen and the treatment was well tolerated, additional doses could be administered to additional lobes.
RESULTS: Twenty-five patients were treated at doses between 2 x 10(9) and 2 x 10(12) vp. At 2 x 10(12) vp, one patient experienced grade 4 pulmonary toxicity, and one patient died 25 days after his second cycle; therefore, a cohort of 10 patients was treated at the recommended phase II dose of 5 x 10(11) vp, with no grade 4 toxicity observed. The most frequent toxicities included low-grade fever, hypoxia, and dyspnea. Of the 23 assessable patients, 16 had stable disease as their best response. Subjective improvement in breathing was noted in eight patients. Limited distribution of vector was observed, with transient detection in patient sputum for 1 to 2 days after administration.
CONCLUSION: Ad-p53 can be administered safely by BAL at 5 x 10(11) vp with repeated dosing. Stabilization of disease and symptomatic improvement may warrant further studies of Ad-p53 or other adenoviruses administered by BAL in patients with BAC.
DOI of Published Version
10.1200/JCO.2007.15.6927
Source
J Clin Oncol. 2008 Sep 1;26(25):4166-71. Link to article on publisher's site
Journal/Book/Conference Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Related Resources
PubMed ID
18757331
Repository Citation
Keedy VL, Wang W, Schiller JH, Chada S, Slovis BS, Coffee K, Worrell JA, Thet LA, Johnson DH, Carbone DP. (2008). Phase I study of adenovirus p53 administered by bronchoalveolar lavage in patients with bronchioloalveolar cell lung carcinoma: ECOG 6597. GSBS Student Publications. https://doi.org/10.1200/JCO.2007.15.6927. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1551