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.
OBJECTIVE
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.


METHODS
TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 x 10(7) particle units [pu] to 4 x 10(11) 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.


CONCLUSIONS
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.
Senzer
Neil
N
US Oncology, Dallas, TX, USA.
Mani
Sridhar
S
Rosemurgy
Alexander
A
Nemunaitis
John
J
Cunningham
Casey
C
Guha
Chandan
C
Bayol
Natalia
N
Gillen
Michelle
M
Chu
Karen
K
Rasmussen
Camilla
C
Rasmussen
Henrik
H
Kufe
Donald
D
Weichselbaum
Ralph
R
Hanna
Nader
N
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D011878:Radiotherapy; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha