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

Authors

• 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

Publication/Presentation Date

9-1-2004

Abstract

PURPOSE: TNFerade is a second-generation replication-deficient adenovector carrying a transgene encoding human tumor necrosis factor alpha 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 x 10(9) -4 x 10(11) 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 alpha 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 cm(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.

Volume

10

Issue

17

First Page

5747

Last Page

5753

ISSN

1078-0432

Published In/Presented At

Mundt, A. J., Vijayakumar, S., Nemunaitis, J., Sandler, A., Schwartz, H., Hanna, N., Peabody, T., Senzer, N., Chu, K., Rasmussen, C. S., Kessler, P. D., Rasmussen, H. S., Warso, M., Kufe, D. W., Gupta, T. D., & Weichselbaum, R. R. (2004). A Phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities. Clinical cancer research : an official journal of the American Association for Cancer Research, 10(17), 5747–5753. https://doi.org/10.1158/1078-0432.CCR-04-0296

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

15355902

Department(s)

Administration and Leadership

Document Type

Article