Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy

Vermorken, Jan B.; Trigo, José; Hitt, Ricardo; Koralewski, P.; Díaz-Rubio, Eduardo; Rolland, Frédéric; Knecht, Rainald; Amellal, Nadia; Schueler, Armin; Baselga, J.

doi:10.1200/jco.2006.06.7447

Cited by 881 publications

(583 citation statements)

References 26 publications

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“…Preclinical studies to treat HNSCCs have been conducted to address this issue because both EGFR and NF-kB activity are enhanced in a high percentage of these malignancies [58]. The EGFR-targeting cetuximab used in combination with radiation prolonged overall survival but failed to reduce the incidence of metastasis, and the response rate with cetuximab administered alone is not above 13% [59]. One mechanism underlying resistance to cetuximab results from the expression of the EGFRvIII mutant, which has a truncated ligand-binding domain, and signals to Lyn, a member of the SRC family of kinases and to STAT3 in up to 42% cases of HNSCC [60,61].…”

Section: Reviewmentioning

confidence: 99%

EGFR and NF-κB: partners in cancer

Shostak

Chariot

2015

Trends in Molecular Medicine

184

160

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Section: Reviewmentioning

confidence: 99%

EGFR and NF-κB: partners in cancer

Shostak

Chariot

2015

Trends in Molecular Medicine

184

160

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“…As such, the inhibition of EGFR signaling has emerged as an important antitumor treatment strategy. Cetuximab (also known as Erbitux or C225) is a recombinant chimeric human-murine monoclonal antibody and is among the most promising and clinically effective of these agents (8)(9)(10). Cetuximab binds EGFR with high affinity and prevents receptor activation, thereby suppressing proliferation and angiogenesis and promoting antibody-dependent cellular toxicity (11).…”

Section: Introductionmentioning

confidence: 99%

Cetuximab inhibits cisplatin-induced activation of EGFR signaling in esophageal squamous cell carcinoma

et al. 2014

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Abstract.A malignant esophageal cancer, squamous cell carcinoma is one of the most prevalent cancers. Despite the use of present surgical techniques combined with various treatment modalities, the overall 5-year survival rate remains at 15-34%. Epidermal growth factor receptor (EGFR) is the most well studied receptor in various cancers and EGFR overexpression is detected in 40% of esophageal squamous cell carcinomas (ESCCs) and ESCC cell lines. To examine the EGFR antibody combination effect, we used treatment with cisplatin and cetuximab in ESCC cell lines, TE-4 and TE-8. Combination of cetuximab and cisplatin resulted in a growth inhibition only in the EGFR overexpressed TE-8 cell line. Furthermore, we confirmed that cisplatin-induced EGFR activation was inhibited by cetuximab in TE-8 but not in TE-4 cells. Our data suggest that cetuximab combined with cisplatin exerts antitumorigenic effects in vitro and in vivo via suppression of EGF signaling, which can be applied toward targeted ESCC treatments.

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“…There are currently two treatment options using anti-EGFR agents under clinical development: a monoclonal antibody directed at the extracellular domain of the receptor and small molecule inhibitors of the EGFR tyrosine kinase. Clinical trials with a humanised murine chimeric monoclonal antibody to EGFR (C225, Cetuximab) in combination with chemotherapy or radiotherapy have shown significant clinical activity in advanced colorectal carcinomas (Cunningham et al, 2004) squamous cell carcinomas of the head and neck (Vermorken et al, 2007), and non-small cell lung cancer (NSCLC) (Janne et al, 2004;Giaccone, 2005). On the other hand, a large number of inhibitors of the EGFR tyrosine kinase are active against NSCLC (Thatcher et al, 2005) and pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Carcinoma of an unknown primary: are EGF receptor, Her-2/neu, and c-Kit tyrosine kinases potential targets for therapy?

et al. 2007

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Carcinomas of an unknown primary site (CUP) are heterogeneous tumours with a median survival of only 8 months. Tyrosine kinase inhibitors are promising new drugs. The aim of this study was to determine the expression of EGF-receptor, Her-2/neu, and c-Kit tyrosine kinases in CUP. Paraffin-embedded specimens were obtained from 54 patients with a CUP who were included in the GEFCAPI 01 randomised phase II trial. Immunohistochemistry was performed using the Dako autostainer with antibodies directed against HER-2/neu protein, EGFR protein, and c-Kit protein (CD117). EGFR expression was found in 36 out of 54 samples (66%). In contrast, Her-2/neu overexpression and c-Kit positivity were only detected in 4 and 10% of patients, respectively. No significant association was found between the expression of the tyrosine kinase receptors and prognosis. EGFR expression was significantly associated with response to cisplatin-based chemotherapy: the response rates were 50 and 22% in patients with EGFR-positive tumours and EGFR-negative tumours, respectively (Po0.05). This study shows that EGFR is frequently expressed in CUP. This finding may prompt clinical trials investigating EGFR inhibitors in this setting. In contrast, c-Kit expression and Her-2/neu overexpression occur infrequently in CUP. EGFR expression was correlated to tumour chemosensitivity.

show abstract

Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy

Abstract: Single-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.

Cited by 881 publications

References 26 publications

EGFR and NF-κB: partners in cancer

EGFR and NF-κB: partners in cancer

Cetuximab inhibits cisplatin-induced activation of EGFR signaling in esophageal squamous cell carcinoma

Carcinoma of an unknown primary: are EGF receptor, Her-2/neu, and c-Kit tyrosine kinases potential targets for therapy?

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