title: Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer.
abstract: OBJECTIVE
  The primary objective of this study was to evaluate the safety and tolerability of a formulated IL-12 plasmid administered intraperitoneally (IP) in conjunction with intravenous (IV) carboplatin/docetaxel in platinum-sensitive ovarian cancer patients.
  
  
  METHODS
  Escalating doses of IL-12 plasmid (phIL-12) formulated with the lipopolymer PEG-PEI-Cholesterol (PPC) were administered IP every 10-11 days for a total of four treatments and the highest dose was expanded to eight treatments. Patients also received IV carboplatin (AUC 5) and docetaxel (75 mg/m(2)) every 21 days. Patients were followed for safety, biological activity and antitumor activity after phIL-12/PPC treatment.
  
  
  RESULTS
  All 13 patients enrolled in the study received both phIL-12/PPC and chemotherapy treatment. There were 49 plasmid-associated adverse events (AEs). The most common AEs were abdominal pain, transient hypotension, low grade fever, catheter site pain, chills, dysgeusia, infusion-related reaction, and nausea. These AEs appeared to be plasmid dose related. Grade 3 AEs included manageable abdominal pain and cytokine release syndrome. There were no dose limiting toxicities and the plasmid treatment did not augment the chemotherapy-associated AEs. The best overall antitumor response (17% CR, 33% PR, 42% SD and 8% PD) was typical of the patient population enrolled for the study. Translational studies showed rise in IFN-γ and TNF-α concentrations in a dose dependent manner.
  
  
  CONCLUSIONS
  The escalating doses and cycles of intraperitoneal phIL-12/PPC when combined with carboplatin/docetaxel chemotherapy in recurrent ovarian cancer patients were well tolerated and did not appear to exacerbate the side effects or attenuate the efficacy of the chemotherapy treatment.
authors.affiliation: EGEN, Inc., Huntsville, AL, USA. Electronic address: kanwer@egeninc.com.
authors.forename: Khursheed
authors.initials: K
authors.lastname: Anwer
authors.forename: F Joseph
authors.initials: FJ
authors.lastname: Kelly
authors.forename: Christina
authors.initials: C
authors.lastname: Chu
authors.forename: Jason G
authors.initials: JG
authors.lastname: Fewell
authors.forename: Danny
authors.initials: D
authors.lastname: Lewis
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D023341:Chills / Q000139:chemically induced; D000077143:Docetaxel; D004408:Dysgeusia / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D015316:Genetic Therapy; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D018664:Interleukin-12 / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010957:Plasmids / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D018664:Interleukin-12; D016190:Carboplatin
keywords: Chemotherapy; Gene therapy; Interleukin-12; Ovarian cancer; Plasmid DNA