title: Phase I/II and phase II studies of targeted gene delivery in vivo: intravenous Rexin-G for chemotherapy-resistant sarcoma and osteosarcoma.
abstract: Rexin-G, a pathotropic nanoparticle bearing a cytocidal cyclin G1 construct was tested in a phase I/II study for chemotherapy-resistant sarcomas and a phase II study for chemotherapy-resistant osteosarcoma. Twenty sarcoma patients and 22 osteosarcoma patients received escalating doses of Rexin-G intravenously from 8 x 10(11) to 24 x 10(11) colony forming units (cfu)/cycle. Treatment was continued if there was <or= 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 the phase I/II study, 3/6 patients had stable disease (SD) at the lowest dose; median progression-free survival (PFS) was 1.2 months, and overall survival (OS), 3.3 months. At higher doses, 10/14 patients had SD; median PFS was 3.7 months and median OS, 7.8 months. In this phase I/II study, a dose-response relationship with Rexin-G dosage was observed for progression-free and OS times (P = 0.02 and 0.005, respectively). In the phase II study, 10/17 evaluable patients had SD, median PFS was >or=3 months and median OS, 6.9 months. These studies suggest that Rexin-G is safe, may help control tumor growth, and may possibly improve survival in chemotherapy-resistant sarcoma and osteosarcoma.
authors.affiliation: The Sarcoma Oncology Center, Santa Monica, California, USA. santchawla@aol.com
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: Doris
authors.initials: D
authors.lastname: Quon
authors.forename: Andreh
authors.initials: A
authors.lastname: Saralou
authors.forename: William C
authors.initials: WC
authors.lastname: Blackwelder
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Hall
authors.forename: Erlinda M
authors.initials: EM
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000235:genetics / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000628:therapy*; D012190:Retroviridae / Q000235:genetics*; D012509:Sarcoma / Q000628:therapy*; D055815:Young Adult
chemical_list: C534702:CCNG1 protein, human; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins