title: Phase-I clinical trial of IL-12 plasmid/lipopolymer complexes for the treatment of recurrent ovarian cancer.
abstract: A phase-I trial to assess the safety and tolerability of human interleukin-12 (IL-12) plasmid (phIL-12) formulated with a synthetic lipopolymer, polyethyleneglycol-polyethyleneimine-cholesterol (PPC), was conducted on women with chemotherapy-resistant recurrent ovarian cancer. A total of 13 patients were enrolled in four dose-escalating cohorts and treated with 0.6, 3, 12 or 24 mg m(-2) of the formulated plasmid once every week for 4 weeks. Administration of phIL-12/PPC was generally safe and well-tolerated. Common side effects included low-grade fever and abdominal pain. Stable disease and reduction in serum CA-125 levels were clinically observed in some patients. Measurable levels of IL-12 plasmid were detectable in PF samples collected throughout the course of phIL-12/PPC treatment. In comparison, serum samples either did not contain detectable amounts of plasmid DNA or contained <1% of the amount found in the corresponding PF samples. Treatment-related increases in IFN-gamma levels were observed in PF but not in serum. These data demonstrate that IL-12 gene delivery with a synthetic delivery system is feasible for ovarian cancer patients.
authors.affiliation: EGEN Inc, Huntsville, AL 35806, USA.
authors.forename: K
authors.initials: K
authors.lastname: Anwer
authors.forename: M N
authors.initials: MN
authors.lastname: Barnes
authors.forename: J
authors.initials: J
authors.lastname: Fewell
authors.forename: D H
authors.initials: DH
authors.lastname: Lewis
authors.forename: R D
authors.initials: RD
authors.lastname: Alvarez
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000628:therapy*; D000328:Adult; D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D018269:Carcinoma, Endometrioid / Q000628:therapy*; D002784:Cholesterol / Q000627:therapeutic use; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000627:therapeutic use
chemical_list: D018394:CA-125 Antigen; D018664:Interleukin-12; D011092:Polyethylene Glycols; D007371:Interferon-gamma; D011094:Polyethyleneimine; D002784:Cholesterol