A phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities

Arno J. Mundt*, Srinivasan Vijayakumar, John Nemunaitis, Alan Sandler, Herbert Schwartz, Nader Hanna, Terrence Peabody, Neil Senzer, Karen Chu, Camilla S. Rasmussen, Paul D. Kessler, Henrik S. Rasmussen, Michael Warso, Donald W. Kufe, Tapas Das Gupta, Ralph R. Weichselbaum

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


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 with 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 (<15 pg/mL). No patients had virus-detected blood, sputum, or urine cultures. Of the 13 evaluable patients, 11 received TNFerade preoperatively, and 2 received the treatment for palliation. Eleven patients (85%) showed objective or pathological tumor responses (2 complete and 9 partial), and 1 had stable disease. Partial responses were achieved despite some of these tumors being very large (up to 675 cm2). 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.

Original languageEnglish (US)
Pages (from-to)5747-5753
Number of pages7
JournalClinical Cancer Research
Issue number17
StatePublished - Sep 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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