A Phase I Trial of TNFerade Biologic in Patients with Soft Tissue Sarcoma in the Extremities

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Abstract
Purpose: TNFerade is a second-generation replication-deficient adenovector carrying a transgene encoding human tumor necrosis factor α under control of a radiation- induced promoter. The objective of this study was to assess the tolerance of combining TNFerade and radiation therapy in patients with soft tissue sarcomas of the extremity. Experimental Design: TNFerade was administered in combination with single-daily fractionated radiation therapy in 14 patients with soft tissue sarcoma of the extremities. Three escalating dose levels of TNFerade (4 × 109 −4 × 1011 particle units) were planned, given in 1 log increments by intratumoral injections, twice weekly during week 1 and once weekly during weeks 2–5 of radiation therapy. Results: TNFerade was well tolerated with no dose-limiting toxicities noted. Grade 1–2 chills (50.0%), fever (43.0%), fatigue (36.0%), and flu-like symptoms (21.0%) were the most common side effects. Serum-tumor necrosis factor α levels were low in all of the patients (2). Of the 11 patients who underwent surgery, 10 (91%) showed a pathological complete response/partial response. Conclusion: TNFerade + radiation therapy was well tolerated in the treatment of patients with soft-tissue sarcoma of the extremity. The high number of objective responses observed warrants additional studies of this approach in a larger controlled prospective trial.

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