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Article: Intratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms

TitleIntratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms
Authors
Issue Date2009
Citation
Journal of Clinical Oncology, 2009, v. 27 n. 8, p. 1235-1242 How to Cite?
AbstractPurpose Squamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS. Patients and Methods Patients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 μg/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry. Results Seventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR + PR + SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P = .0312 and P = .095, respectively). Conclusion Intratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects. Copyright © 2009 by the American Society of Clinical Oncology. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/194233
ISSN
2015 Impact Factor: 20.982
2015 SCImago Journal Rankings: 9.204
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGrandis, JR-
dc.contributor.authorLai, SY-
dc.contributor.authorKoppikar, P-
dc.contributor.authorThomas, SM-
dc.contributor.authorChilds, EE-
dc.contributor.authorEgloff, AM-
dc.contributor.authorSeethala, RR-
dc.contributor.authorBranstetter, BF-
dc.contributor.authorGooding, WE-
dc.contributor.authorMuthukrishnan, A-
dc.contributor.authorMountz, JM-
dc.contributor.authorLui, VWY-
dc.contributor.authorShin, DM-
dc.contributor.authorAgarwala, SS-
dc.contributor.authorJohnson, R-
dc.contributor.authorCouture, LA-
dc.contributor.authorMyers, EN-
dc.contributor.authorJohnson, JT-
dc.contributor.authorMills, G-
dc.contributor.authorArgiris, A-
dc.date.accessioned2014-01-30T03:32:20Z-
dc.date.available2014-01-30T03:32:20Z-
dc.date.issued2009-
dc.identifier.citationJournal of Clinical Oncology, 2009, v. 27 n. 8, p. 1235-1242-
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/194233-
dc.description.abstractPurpose Squamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS. Patients and Methods Patients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 μg/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry. Results Seventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR + PR + SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P = .0312 and P = .095, respectively). Conclusion Intratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects. Copyright © 2009 by the American Society of Clinical Oncology. All rights reserved.-
dc.languageeng-
dc.relation.ispartofJournal of Clinical Oncology-
dc.titleIntratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1200/JCO.2008.17.8251-
dc.identifier.pmid19204206-
dc.identifier.scopuseid_2-s2.0-62449303549-
dc.identifier.volume27-
dc.identifier.issue8-
dc.identifier.spage1235-
dc.identifier.epage1242-
dc.identifier.isiWOS:000266193700018-
dc.identifier.f10001166550-

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