Purpose: preclinical studies have demonstrated that the adenovirus type 5 E
IA gene is associated with antitumor activities by transcriptional repressi
on of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is kno
wn to induce regression of HER-2/neu-overexpressing breast and ovarian canc
ers in nude mice. Therefore, we evaluated the feasibility of intracavitary
injection of EIA gene complexed with DC-Chol cationic liposome (DCC-E1A) in
patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing b
reast and ovarian cancers in a phase I clinical trial.
Patients and Methods: An EIA gene complexed with DCC-E1A cationic liposome
was injected once a week into the thoracic or peritoneal cavity of 18 patie
nts with advanced cancer of:the breast (n = 6) or ovary(n = 12).
Results: ETA gene expression in tumor cells was detected by immunohistochem
ical staining and reverse transcriptase-polymerase chain reaction. This E1A
gene expression wets accompanied by HER-2/neu down-regulation, increased a
poptosis, and reduced proliferation. The most common treatment-related toxi
cities were fever, nausea, vomiting, and/or discomfort at the injection sit
Conclusion: These results argue for the feasibility of intracavitary DCC-E1
A administration, provide a clear proof of preclinical concept, and warrant
phase II trials to determine the antitumor activity of the EIA gene. (C) 2
001 by American Society of Clinical Oncology.