Cetuximab in squamous cell head and neck carcinomas

Gebbia, Vittorio; Giuliani, Francesco; Valori, Vanna Maria; Agueli, R.; Colucci, Giuseppe; Maiello, Evaristo

doi:10.1093/annonc/mdm215

Cited by 14 publications

(10 citation statements)

References 17 publications

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“…Clearly, alternative forms of treatment are required. Nonconjugated monoclonal antibody therapy to epidermal growth factor receptor (Cetuximab) has undergone clinical trials in combination with radiotherapy with some success [29][30][31][32]. However, efficacy and toxicity studies comparing Cetuximab with standard chemoradiotherapy treatments in larger trials are currently under way [32,33].…”

Section: Discussionmentioning

confidence: 99%

A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck

et al. 2008

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VB4-845 is a novel recombinant fusion protein that targets the epithelial cellular adhesion molecule (EpCAM). This initial clinical trial was conducted to determine the maximum tolerated dose of intratumoral injections in patients with advanced squamous cell carcinoma of the head and neck and to assess pharmacokinetics and immunogenicity. Twenty-four patients with advanced, recurrent squamous cell carcinoma of the head and neck received two cycles of five daily intratumoral VB4-845 injections of 20, 40, 80, 130, 200, or 280 microg. The maximum tolerated dose was established to be 280 microg administered daily for 5 days. Common adverse events were pain due to intratumoral injection and reversibly elevated liver enzymes. Of the 24 patients, 15 had detectable blood levels with a mean drug half-life of 4.0 +/- 0.3 h. VB4-845 reduced or stabilized tumors in 71.4% of epithelial cell adhesion molecule-positive patients. VB4-845 intratumoral injection therapy was well tolerated and feasible.

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Section: Discussionmentioning

confidence: 99%

A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck

et al. 2008

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“…The antitumor effect of cetuximab combined with chemotherapy is reported for treating colorectal cancer and HNSCC. ( 4,5 ) Cetuximab combined with radiotherapy is also effective in patients with locally advanced HNSCC. ( 6 ) Cetuximab binds to EGFR with a 10‐fold higher affinity than its natural ligands and prevents ligand‐induced phosphorylation of EGFR.…”

mentioning

confidence: 99%

Gene status of head and neck squamous cell carcinoma cell lines and cetuximab‐mediated biological activities

et al. 2011

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Cetuximab is a chimeric IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR). Cetuximab binds to EGFR and prevents phosphorylation of EGFR. Moreover, preclinical results have shown the ability of cetuximab to induce either complement-mediated tumor cell killing (CDC) or antibody-dependent cell-mediated-cytotoxicity (ADCC). We previously reported mutation in EGFR regarding head and neck squamous cell carcinoma (HNSCC) cell lines. In the present study, we analyzed the same 16 HNSCC cell lines for mutations in KRAS, PIK3CA, BRAF and PTEN. Furthermore, we evaluated cetuximab-mediated biological activities (antiproliferative effect by the MTT assay and ADCC) regarding these cell lines. Mutations in PIK3CA and PTEN were observed in two cell lines (2 ⁄ 16, 12.5%), but no mutation was observed in KRAS and BRAF. The antiproliferative effect of cetuximab by the MTT assay was not strong, and no correlation was observed between the antiproliferative effect of cetuximab and mutations in EGFR, KRAS, PIK3CA, BRAF and PTEN in these cell lines. Therefore, the mutation status of EGFR and downstream molecules were not useful for predicting the antitumor effects of cetuximab on HNSCC. Cetuximab-mediated ADCC was observed in these cell lines and might have been influenced by the expression of EGFR. Therefore, cetuximab-mediated ADCC seems to be an important part of the antitumor mechanisms of cetuximab and the expression levels of EGFR might influence the antitumor activity of cetuximab. Therefore, besides the antiproliferative effect of cetuximab by the MTT assay, it appeared important to evaluate cetuximabmediated ADCC as well as

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“…It is a human-mouse chimeric antibody of the IgG1 subclass, and is clinically administered as an intravenous infusion. Currently, cetuximab has been approved by the Food and Drug Agency (FDA) as a therapeutic agent for metastatic colorectal cancer (14) and head and neck cancer (15), and used clinically.…”

Section: Discussionmentioning

confidence: 99%

Cetuximab inhibits growth, peritoneal dissemination, and lymph node and lung metastasis of endometrial cancer, and prolongs host survival

Takahashi

Saga²,

Mizukami³

et al. 2009

Int J Oncol

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Abstract. The purpose of this study was to explore the possibility of molecular-targeted therapy with anti-epidermal growth factor receptor (EGFR) antibody (cetuximab) for endometrial cancer to develop a new treatment for advanced endometrial cancer. We analyzed EGFR protein expression and gene mutations in the human endometrial cancer cell line HEC1A, and evaluated the in vitro and in vivo effects of cetuximab on HEC1A. EGFR expression was observed in HEC1A cells, but no mutations in the EGFR gene were detected. Cetuximab inhibited HEC1A cell growth and invasion and VEGF-A production in vitro, and HECIA cell tumor growth, its peritoneal dissemination with ascites, and lymph node and lung metastasis in vivo. In addition, the antibody prolonged the survival of a mouse model of systemic metastasis. These results suggest the possibility of molecular-targeted therapy using cetuximab for endometrial cancer.

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Cetuximab in squamous cell head and neck carcinomas

Cited by 14 publications

References 17 publications

A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck

A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck

Gene status of head and neck squamous cell carcinoma cell lines and cetuximab‐mediated biological activities

Cetuximab inhibits growth, peritoneal dissemination, and lymph node and lung metastasis of endometrial cancer, and prolongs host survival

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