title: A Phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Chicago Medical Center, Chicago, Illinois, USA. amundt@radonc.uchicago.edu
authors.forename: Arno J
authors.initials: AJ
authors.lastname: Mundt
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Vijayakumar
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwartz
authors.forename: Nader
authors.initials: N
authors.lastname: Hanna
authors.forename: Terrence
authors.initials: T
authors.lastname: Peabody
authors.forename: Neil
authors.initials: N
authors.lastname: Senzer
authors.forename: Karen
authors.initials: K
authors.lastname: Chu
authors.forename: Camilla S
authors.initials: CS
authors.lastname: Rasmussen
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kessler
authors.forename: Henrik S
authors.initials: HS
authors.lastname: Rasmussen
authors.forename: Michael
authors.initials: M
authors.lastname: Warso
authors.forename: Donald W
authors.initials: DW
authors.lastname: Kufe
authors.forename: Tapas Das
authors.initials: TD
authors.lastname: Gupta
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha