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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.

Publication ,  Journal Article
Seiwert, TY; Darga, T; Haraf, D; Blair, EA; Stenson, K; Cohen, EEW; Salama, JK; Villaflor, V; Witt, ME; Lingen, MW; Weichselbaum, RR; Vokes, EE
Published in: Annals of oncology : official journal of the European Society for Medical Oncology
March 2013

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

Duke Scholars

Published In

Annals of oncology : official journal of the European Society for Medical Oncology

DOI

EISSN

1569-8041

ISSN

0923-7534

Publication Date

March 2013

Volume

24

Issue

3

Start / End Page

769 / 776

Related Subject Headings

  • Treatment Outcome
  • Squamous Cell Carcinoma of Head and Neck
  • Retreatment
  • Radiotherapy, Intensity-Modulated
  • Radiotherapy Planning, Computer-Assisted
  • Radiation-Sensitizing Agents
  • Oncology & Carcinogenesis
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
 

Citation

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Seiwert, T. Y., Darga, T., Haraf, D., Blair, E. A., Stenson, K., Cohen, E. E. W., … Vokes, E. E. (2013). 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. Annals of Oncology : Official Journal of the European Society for Medical Oncology, 24(3), 769–776. https://doi.org/10.1093/annonc/mds523
Seiwert, T. Y., T. Darga, D. Haraf, E. A. Blair, K. Stenson, E. E. W. Cohen, J. K. Salama, et al. “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.Annals of Oncology : Official Journal of the European Society for Medical Oncology 24, no. 3 (March 2013): 769–76. https://doi.org/10.1093/annonc/mds523.
Seiwert TY, Darga T, Haraf D, Blair EA, Stenson K, Cohen EEW, et al. 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. Annals of oncology : official journal of the European Society for Medical Oncology. 2013 Mar;24(3):769–76.
Seiwert, T. Y., et al. “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.Annals of Oncology : Official Journal of the European Society for Medical Oncology, vol. 24, no. 3, Mar. 2013, pp. 769–76. Epmc, doi:10.1093/annonc/mds523.
Seiwert TY, Darga T, Haraf D, Blair EA, Stenson K, Cohen EEW, Salama JK, Villaflor V, Witt ME, Lingen MW, Weichselbaum RR, Vokes EE. 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. Annals of oncology : official journal of the European Society for Medical Oncology. 2013 Mar;24(3):769–776.
Journal cover image

Published In

Annals of oncology : official journal of the European Society for Medical Oncology

DOI

EISSN

1569-8041

ISSN

0923-7534

Publication Date

March 2013

Volume

24

Issue

3

Start / End Page

769 / 776

Related Subject Headings

  • Treatment Outcome
  • Squamous Cell Carcinoma of Head and Neck
  • Retreatment
  • Radiotherapy, Intensity-Modulated
  • Radiotherapy Planning, Computer-Assisted
  • Radiation-Sensitizing Agents
  • Oncology & Carcinogenesis
  • Middle Aged
  • Maximum Tolerated Dose
  • Male