title: Phase I study of adenovirus p53 administered by bronchoalveolar lavage in patients with bronchioloalveolar cell lung carcinoma: ECOG 6597.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Keedy
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Joan
authors.initials: J
authors.lastname: Schiller
authors.forename: Sunil
authors.initials: S
authors.lastname: Chada
authors.forename: Bonnie
authors.initials: B
authors.lastname: Slovis
authors.forename: Keith
authors.initials: K
authors.lastname: Coffee
authors.forename: John
authors.initials: J
authors.lastname: Worrell
authors.forename: Lyn A
authors.initials: LA
authors.lastname: Thet
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
authors.forename: David P
authors.initials: DP
authors.lastname: Carbone