Abstract
Purpose: TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy. Patients and Methods: TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 × 107 particle units [pu] to 4 × 1011 pu) in patients with solid tumors being treated with radiation. Results: Thirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed. Conclusion: This is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 592-601 |
| Number of pages | 10 |
| Journal | Journal of Clinical Oncology |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene : A phase I study in patients with solid tumors. / Senzer, Neil; Mani, Sridhar; Rosemurgy, Alexander; Nemunaitis, John; Cunningham, Casey; Guha, Chandan; Bayol, Natalia; Gillen, Michelle; Chu, Karen; Rasmussen, Camilla; Rasmussen, Henrik; Kufe, Donald; Weichselbaum, Ralph; Hanna, Nader.
In: Journal of Clinical Oncology, Vol. 22, No. 4, 2004, p. 592-601.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene
T2 - A phase I study in patients with solid tumors
AU - Senzer, Neil
AU - Mani, Sridhar
AU - Rosemurgy, Alexander
AU - Nemunaitis, John
AU - Cunningham, Casey
AU - Guha, Chandan
AU - Bayol, Natalia
AU - Gillen, Michelle
AU - Chu, Karen
AU - Rasmussen, Camilla
AU - Rasmussen, Henrik
AU - Kufe, Donald
AU - Weichselbaum, Ralph
AU - Hanna, Nader
PY - 2004
Y1 - 2004
N2 - Purpose: TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy. Patients and Methods: TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 × 107 particle units [pu] to 4 × 1011 pu) in patients with solid tumors being treated with radiation. Results: Thirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed. Conclusion: This is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.
AB - Purpose: TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy. Patients and Methods: TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 × 107 particle units [pu] to 4 × 1011 pu) in patients with solid tumors being treated with radiation. Results: Thirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed. Conclusion: This is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.
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U2 - 10.1200/JCO.2004.01.227
DO - 10.1200/JCO.2004.01.227
M3 - Article
VL - 22
SP - 592
EP - 601
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 4
ER -