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Phase I/II and Phase II Studies of Targeted Gene Delivery In Vivo: Intravenous Rexin-G for Chemotherapy-resistant Sarcoma and Osteosarcoma

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 int...

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Detalles Bibliográficos
Autores principales: Chawla, Sant P, Chua, Victoria S, Fernandez, Lita, Quon, Doris, Saralou, Andreh, Blackwelder, William C, Hall, Frederick L, Gordon, Erlinda M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835268/
https://www.ncbi.nlm.nih.gov/pubmed/19532136
http://dx.doi.org/10.1038/mt.2009.126
Descripción
Sumario: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 × 10(11) to 24 × 10(11) colony forming units (cfu)/cycle. Treatment was continued if there was ≤ 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 ≥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.