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
; 24(3): 769-76, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23104721
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
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DNA
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Carcinoma de Células Escamosas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias de Cabeça e Pescoço
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article