Annals of surgical oncology · 2005
TNFerade, an adenovector carrying the transgene for human tumor necrosis factor alpha, for patients with advanced solid tumors: surgical experience and long-term follow-up.
Клиническое исследование I фазыСтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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McLoughlin James M, McCarty Todd M, Cunningham Casey, Clark Valerie, Senzer Neil, Nemunaitis John, Kuhn Joseph A
Аннотация
BACKGROUND: Over the last several years, attempts have been made to use the tumoricidal effects of tumor necrosis factor (TNF)-alpha to treat cancer. Many of these studies demonstrated dose-limiting systemic side effects from high concentrations of TNF-alpha. The recent focus has been on developing a local delivery system for TNF-alpha to minimize the systemic response.
METHODS: This study was part of a phase I open-label multi-institutional trial using TNFerade. We focus on the patients treated at Baylor University Medical Center and provide postoperative and long-term follow-up. TNFerade uses a second-generation nonreplicating adenovirus as the vector for delivery of the human transgene TNF-alpha. An early growth response 1 promoter was placed upstream from the TNF-alpha gene. This promoter is activated by ionizing radiation, thus allowing for temporal and spatial control of TNF-alpha release. Tumors were injected over 5 weeks with ionizing radiation given 3 days after injections for 6 weeks. Tumor response was measured by computed tomographic imaging and physical examination.
RESULTS: As described in our original experience, no patients experienced dose-limiting toxicities up to doses of 4 x 10(11) particles per injection. Tumors injected demonstrated a response independently of histology. Four patients had complete regression of the tumor injected. Three patients with complete regression have survived > or = 2 years from the time of treatment.
CONCLUSIONS: Both short-term and long-term safety are observed with TNFerade. These data demonstrate the need for phase II trials.
METHODS: This study was part of a phase I open-label multi-institutional trial using TNFerade. We focus on the patients treated at Baylor University Medical Center and provide postoperative and long-term follow-up. TNFerade uses a second-generation nonreplicating adenovirus as the vector for delivery of the human transgene TNF-alpha. An early growth response 1 promoter was placed upstream from the TNF-alpha gene. This promoter is activated by ionizing radiation, thus allowing for temporal and spatial control of TNF-alpha release. Tumors were injected over 5 weeks with ionizing radiation given 3 days after injections for 6 weeks. Tumor response was measured by computed tomographic imaging and physical examination.
RESULTS: As described in our original experience, no patients experienced dose-limiting toxicities up to doses of 4 x 10(11) particles per injection. Tumors injected demonstrated a response independently of histology. Four patients had complete regression of the tumor injected. Three patients with complete regression have survived > or = 2 years from the time of treatment.
CONCLUSIONS: Both short-term and long-term safety are observed with TNFerade. These data demonstrate the need for phase II trials.