BACKGROUND: TNFeradeBiologic (AdGVEGR.TNF.11D) is a replication-deficient adenoviral vector that expresses tumor necrosis factor-α (TNF-α) under the control of the Egr-1 promoter, which is inducible by chemotherapy and radiation. OBJECTIVE: This study was conducted to determine the maximal tolerated dose of TNFeradeBiologic with standard chemoradiotherapy and preliminary activity and safety of the combination in the treatment of locally advanced pancreatic cancer (LAPC). DESIGN: TNFeradeBiologic was injected into locally advanced pancreatic carcinomas by using EUS or percutaneous administration once a week for 5 weeks together with 50.4 Gy radiation and 5-fluorouracil (5-FU) 200 mg/m(2) daily over 5.5 weeks. Dose levels from 4 × 10(9) to 1 × 10(12) particle units (PU) were studied. SETTING: Multicentered, academic institutions. PATIENTS: Fifty patients with LAPC were treated. INTERVENTIONS: Doses of TNFerade Biologic were administered to patients. MAIN OUTCOME MEASUREMENTS: Toleration of TNFerade Biologic was measured through toxicity and tumor response, by using the criteria of the Response Evaluation Criteria in Solid Tumors and the World Health Organization, and was reviewed by a central radiology facility. Overall survival and progression-free survival were also measured. RESULTS: Dose-limiting toxicities of pancreatitis and cholangitis were observed in 3 patients at the 1 × 10(12) PU dose, making 4 × 10(11) PU the maximum tolerated dose. One complete response, 3 partial responses, and 12 patients with stable disease were noted. Seven patients eventually went to surgery, 6 had clear margins, and 3 survived >24 months. LIMITATIONS: This is a Phase 1/2 non-randomized study. CONCLUSIONS: Intratumoral delivery of TNFerade Biologic by EUS with fine-needle viral injection or percutaneously, combined with chemoradiation, shows promise in the treatment of LAPC. There appeared to be better clinical outcome at the maximal tolerated dose than at lower doses. The dose of 4 ×10(11) PU TNFerade Biologic was generally well tolerated, with encouraging indications of activity, and will be tested in the randomized phase of this study. Delivery of TNFerade Biologic did not interfere with subsequent surgical resection.
BACKGROUND: TNFeradeBiologic (AdGVEGR.TNF.11D) is a replication-deficient adenoviral vector that expresses tumor necrosis factor-α (TNF-α) under the control of the Egr-1 promoter, which is inducible by chemotherapy and radiation. OBJECTIVE: This study was conducted to determine the maximal tolerated dose of TNFeradeBiologic with standard chemoradiotherapy and preliminary activity and safety of the combination in the treatment of locally advanced pancreatic cancer (LAPC). DESIGN: TNFeradeBiologic was injected into locally advanced pancreatic carcinomas by using EUS or percutaneous administration once a week for 5 weeks together with 50.4 Gy radiation and 5-fluorouracil (5-FU) 200 mg/m(2) daily over 5.5 weeks. Dose levels from 4 × 10(9) to 1 × 10(12) particle units (PU) were studied. SETTING: Multicentered, academic institutions. PATIENTS: Fifty patients with LAPC were treated. INTERVENTIONS: Doses of TNFerade Biologic were administered to patients. MAIN OUTCOME MEASUREMENTS: Toleration of TNFerade Biologic was measured through toxicity and tumor response, by using the criteria of the Response Evaluation Criteria in Solid Tumors and the World Health Organization, and was reviewed by a central radiology facility. Overall survival and progression-free survival were also measured. RESULTS: Dose-limiting toxicities of pancreatitis and cholangitis were observed in 3 patients at the 1 × 10(12) PU dose, making 4 × 10(11) PU the maximum tolerated dose. One complete response, 3 partial responses, and 12 patients with stable disease were noted. Seven patients eventually went to surgery, 6 had clear margins, and 3 survived >24 months. LIMITATIONS: This is a Phase 1/2 non-randomized study. CONCLUSIONS: Intratumoral delivery of TNFerade Biologic by EUS with fine-needle viral injection or percutaneously, combined with chemoradiation, shows promise in the treatment of LAPC. There appeared to be better clinical outcome at the maximal tolerated dose than at lower doses. The dose of 4 ×10(11) PUTNFerade Biologic was generally well tolerated, with encouraging indications of activity, and will be tested in the randomized phase of this study. Delivery of TNFerade Biologic did not interfere with subsequent surgical resection.
Authors: P W Pisters; W A Hudec; J E Lee; I Raijman; S Lahoti; N A Janjan; T A Rich; C H Crane; R Lenzi; R A Wolff; J L Abbruzzese; D B Evans Journal: J Clin Oncol Date: 2000-02 Impact factor: 44.544
Authors: Paolo Massucco; Lorenzo Capussotti; Antonella Magnino; Elisa Sperti; Marco Gatti; Andrea Muratore; Enrico Sgotto; Pietro Gabriele; Massimo Aglietta Journal: Ann Surg Oncol Date: 2006-09-06 Impact factor: 5.344
Authors: Christine A Iacobuzio-Donahue; Baojin Fu; Shinichi Yachida; Mingde Luo; Hisashi Abe; Clark M Henderson; Felip Vilardell; Zheng Wang; Jesse W Keller; Priya Banerjee; Joseph M Herman; John L Cameron; Charles J Yeo; Marc K Halushka; James R Eshleman; Marian Raben; Alison P Klein; Ralph H Hruban; Manuel Hidalgo; Daniel Laheru Journal: J Clin Oncol Date: 2009-03-09 Impact factor: 44.544
Authors: T D Chung; H J Mauceri; D E Hallahan; J J Yu; S Chung; W L Grdina; S Yajnik; D W Kufe; R R Weichselbaum Journal: Cancer Gene Ther Date: 1998 Nov-Dec Impact factor: 5.987
Authors: Carlo Fabbri; Carmelo Luigiano; Andrea Lisotti; Vincenzo Cennamo; Clara Virgilio; Giancarlo Caletti; Pietro Fusaroli Journal: World J Gastroenterol Date: 2014-07-14 Impact factor: 5.742
Authors: Margaret G Keane; Konstantinos Bramis; Stephen P Pereira; Giuseppe K Fusai Journal: World J Gastroenterol Date: 2014-03-07 Impact factor: 5.742
Authors: Murali M Yallapu; Mara C Ebeling; Sheema Khan; Vasudha Sundram; Neeraj Chauhan; Brij K Gupta; Susan E Puumala; Meena Jaggi; Subhash C Chauhan Journal: Mol Cancer Ther Date: 2013-05-23 Impact factor: 6.261