title: Advanced phase I/II studies of targeted gene delivery in vivo: intravenous Rexin-G for gemcitabine-resistant metastatic pancreatic cancer.
abstract: Rexin-G, a nonreplicative pathology-targeted retroviral vector bearing a cytocidal cyclin G1 construct, was tested in a phase I/II study for gemcitabine-resistant pancreatic cancer. The patients received escalating doses of Rexin-G intravenously from 1 x 10(11) colony-forming units (cfu) 2-3x a week (dose 0-1) to 2 x 10(11) cfu 3x a week (dose 2) for 4 weeks. Treatment was continued if there was less than or equal to grade 1 toxicity. No dose-limiting toxicity (DLT) was observed, and no vector DNA integration, replication-competent retrovirus (RCR), or vector-neutralizing antibodies were noted. In nine evaluable patients, 3/3 patients had stable disease (SD) at dose 0-1. At dose 2, 1/6 patients had a partial response (PR) and 5/6 patients had SD. Median progression-free survival (PFS) was 3 months at dose 0-1, and >7.65 months at dose 2. Median overall survival (OS) was 4.3 months at dose 0-1, and 9.2 months at dose 2. One-year survival was 0% at dose 0-1 compared to 28.6% at dose 2, suggesting a dose-response relationship between OS and Rexin-G dosage. Taken together, these data indicate that (i) Rexin-G is safe and well tolerated, and (ii) Rexin-G may help control tumor growth, and may possibly prolong survival in gemcitabine-resistant pancreatic cancer, thus, earning US Food and Drug Administration's (FDA) fast-track designation as second-line treatment for pancreatic cancer.
authors.affiliation: Sarcoma Oncology Center, Santa Monica, California, USA.
authors.forename: Sant P
authors.initials: SP
authors.lastname: Chawla
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Chua
authors.forename: Lita
authors.initials: L
authors.lastname: Fernandez
authors.forename: Dorris
authors.initials: D
authors.lastname: Quon
authors.forename: William C
authors.initials: WC
authors.lastname: Blackwelder
authors.forename: Erlinda M
authors.initials: EM
authors.lastname: Gordon
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Hall
mesh_terms: D056766:Cyclin G1 / Q000235:genetics / Q000502:physiology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D012190:Retroviridae / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D056766:Cyclin G1; D003841:Deoxycytidine; D000093542:Gemcitabine