In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 9 ( 2004-05-01), p. 2986-2996
Abstract:
Purpose: HER-2/neu oncogene is overexpressed in 10–30% of epithelial ovarian cancers and is associated with a poor prognosis. The E1A gene product of adenovirus type 5 down-regulates HER-2/neu and causes tumor regression in animal models. In the current study, we sought to determine the toxicity and biological activity of E1A-lipid complex in ovarian cancer patients. Experimental Design: A Phase I trial involving intraperitoneal (i.p.) administration of E1A-lipid complex was initiated in ovarian cancer patients to assess biological activity (E1A gene transfer/transcription/translation and HER-2/neu expression) and to determine the maximum tolerated dose. Successive cohorts received E1A-lipid complex at doses of 1.8, 3.6, and 7.2 mg DNA/m2, given as weekly i.p. infusions for 3 of 4 weeks (each cycle) up to a maximum of six cycles. Peritoneal fluid was sampled at baseline and twice monthly for cellularity, cytology, CA-125, and biological activity Results: Fifteen patients, with a median age of 57 years (range, 43–81) were recruited. Three (1.8 mg DNA/m2), 4 (3.6 mg DNA/m2), and 8 patients (7.2 mg DNA/m2) received i.p. E1A. A total of 91 infusions (range, 1–18) was administered. Abdominal pain was the dose-limiting toxicity, and the maximum-tolerated dose was 3.6 mg DNA/m2. E1A gene transfer and expression was observed in all of the patients and at all of the dose levels. HER-2/neu down-regulation could be demonstrated in the tumor cells of 2 patients (18%). There was no correlation between dose and biological activity. Conclusions: I.P. EIA-lipid complex gene therapy is feasible and safe. Future studies, either alone or in combination with chemotherapy, particularly in patients with minimal residual disease, should be evaluated.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-03-0291
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2004
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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