Originally published as JCO Early Release 10.1200/JCO.2004.01.227 on January 15 2004

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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

From US Oncology, Dallas, TX; Albert Einstein College of Medicine, Bronx, NY; University of South Florida, Tampa, FL; GenVec Inc, Gaithersburg, MD; Department of Medicine, Dana-Farber Cancer Institute, Boston, MA; University of Chicago Medical Center, Chicago, IL; and the Department of General Surgery, University of Kentucky Medical Center, Lexington, KY

Address reprint requests to Nader Hanna, MD, Assisstant Professor of Surgery, University of Kentucky Medical Center, Lexington, KY; e-mail: nhanna1{at}pop.uky.edu.

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 x 10⁷ particle units [pu] to 4 x 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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

Supported by a grant from GenVec Inc, Gaithersburg, MD.

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