A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation

Ann Oncol. 2013 Mar;24(3):769-76. doi: 10.1093/annonc/mds523. Epub 2012 Oct 26.


Background: AdGV.EGR.TNF.11D (TNFerade™ Biologic) is a replication-deficient adenoviral vector expressing human tumor necrosis factor alpha (TNF-α) under the control of the chemoradiation-inducible EGR-1 promoter. TNF-α has been shown to function as a radiation sensitizer. We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TNFerade™ Biologic, when added to chemoradiotherapy in poor prognosis patients with recurrent, previously irradiated head and neck cancer (HNC).

Methods: TNFerade™ Biologic was injected intratumorally on day 1 of each 14-day cycle and dose-escalated in log increments from 4 × 10(9) to 4 × 10(11) PU. Daily radiation, infusional 5-fluorouracil (5-FU), and hydroxyurea were given on days 1-5 for seven cycles (FHX). Tumor biopsies were obtained before, during, and after treatment.

Results: Fourteen patients were treated. DLT was reached at a dose level of 3 (4 × 10(11) PU) with three thrombotic events. The response rate was 83.3%. The median survival was 9.6 months. One patient (7.1%) remained alive 3 years after treatment. Biopsies were obtained in 90% of patients. Nearly all tumors expressed adenovirus receptors, TNF-α, and TNF-α receptors. Adenoviral DNA was detected in three biopsies from one patient.

Conclusions: TNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 × 10(10) PU. Monitoring for thrombotic events is indicated.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy
  • DNA / administration & dosage*
  • DNA / genetics
  • Dose Fractionation, Radiation
  • Female
  • Fluorouracil / administration & dosage
  • Genetic Therapy
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Hydroxyurea / administration & dosage
  • Kaplan-Meier Estimate
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Radiation-Sensitizing Agents / administration & dosage*
  • Radiotherapy Planning, Computer-Assisted
  • Radiotherapy, Intensity-Modulated
  • Retreatment
  • Squamous Cell Carcinoma of Head and Neck
  • Treatment Outcome


  • Radiation-Sensitizing Agents
  • TNFeraseBiologic
  • DNA
  • Fluorouracil
  • Hydroxyurea