Phase-I clinical trial of IL-12 plasmid/lipopolymer complexes for the treatment of recurrent ovarian cancer.
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.
Anwer
K
K
EGEN Inc, Huntsville, AL 35806, USA.
Barnes
M N
MN
Fewell
J
J
Lewis
D H
DH
Alvarez
R D
RD
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
D018394:CA-125 Antigen; D018664:Interleukin-12; D011092:Polyethylene Glycols; D007371:Interferon-gamma; D011094:Polyethyleneimine; D002784:Cholesterol