Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck

Argiris, Athanassios; Κotsakis, Athanasios; Hoang, Tien; Worden, Francis P.; Savvides, P.; Gibson, Michael K.; Gyanchandani, Rekha; Blumenschein, George R.; Chen, H.X.; Grandis, Jennifer R.; Harari, Paul M.; Kies, Merrill S.; Kim, S.

doi:10.1093/annonc/mds245

Cited by 128 publications

(103 citation statements)

References 34 publications

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“…The selective tyrosine kinase inhibitors erlotinib and gefitinib function through EGFR-inhibition. The results of the present study support several previous studies, which suggested that EGFR activation regulates VEGF expression (63)(64)(65). This mechanism may provide an explanation for the decrease in VEGFR-1 expression though selective EGFR-inhibition in HNSCC 11A.…”

Section: ------------------------------------------------------------supporting

confidence: 91%

Effect of selective small molecule inhibitors on MMP-9 and VEGFR-1 expression in p16-positive and -negative squamous cell carcinoma

Kramer

Schultz²,

Hock

et al. 2017

Oncology Letters

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Abstract. The identification of molecular targets in the therapy of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a primary aim of cancer research. Matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor receptor (VEGFR) have important roles in the development of HNSCC. The tyrosine kinase inhibitors, nilotinib, dasatinib, erlotinib and gefitinib are well established in the targeted therapy of tumors other than HNSCC. The present study aimed to investigate the alteration of MMP-9 and VEGFR-1 expression patterns following treatment with these tyrosine kinase inhibitors in p16-positive and -negative squamous carcinoma cells. MMP-9 and VEGFR-1 expression was evaluated using an ELISA in HNSCC 11A, HNSCC 14C and p16-positive CERV196 tumor cell lines, following treatment with nilotinib, dasatinib, erlotinib and gefitinib. A statistically significant reduction in MMP-9 and VEGFR-1 expression was observed in the p16-negative HNSCC 11A cells following treatment with all inhibitors (P<0.05). VEGFR-1 expression was significantly increased in p16-positive SCC cells following treatment with nilotinib, dasatinib, erlotinib and gefitinib (P<0.05). The expression of MMP-9 and VEGFR-1 was significantly altered by treatment with nilotinib, dasatinib, erlotinib and gefitinib in vitro. The results of the present study are attributed to the efficacy of the tested drugs and present potential compensatory strategies of cancer cells to avoid the antiangiogenic properties of the tested tyrosine kinase inhibitors in vitro.

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Section: ------------------------------------------------------------supporting

confidence: 91%

Effect of selective small molecule inhibitors on MMP-9 and VEGFR-1 expression in p16-positive and -negative squamous cell carcinoma

Kramer

Schultz²,

Hock

et al. 2017

Oncology Letters

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“…Numerous drugs are in the early stages of development for HNSCC treatment, including novel anti-EGFR small-molecule tyrosine kinase inhibitors, EGFR antisense molecules, and multiple add-on therapies to radiation and chemotherapy intended to decrease resistance to anti-EGFR agents (42)(43)(44)(45). In addition, numerous other anti-EGFR agents are currently being assessed in phases II and III clinical trials in different HNSCC therapeutic settings (46,47). As the targeted treatment group only had 3/20 patients with high expression of EGFR, the majority of the patients exhibited low expression of EGFR; consequently, those patients were not sensitive to cetuximab and nimotuzumab.…”

Section: Discussionmentioning

confidence: 99%

Prognostic analysis of patients with locally advanced nasopharyngeal carcinoma following intensity modulated radiation therapy

et al. 2018

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Abstract. The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively. Multivariate Cox regression analysis identified that targeted treatment [hazard ratio (95% confidence interval), 2.642 (1.001, 6.972); P=0.0497] served as an independent negative prognostic factor in locally advanced NPC. The results of immunostaining revealed that the staining intensity of the radiation-resistant group was increased compared with that of the radiation-sensitive group. These results demonstrate that a high expression of EGFR may be associated with radiation resistance, and targeted treatment may not be effective in patients with locally advanced nasopharyngeal carcinoma with low expression of EGFR.

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“…Multiple studies have demonstrated evidence of vessel normalization and increased therapeutic uptake. [22][23][24] There are also a series of studies that demonstrate the opposite effect of decreased uptake of therapeutic following anti-VEGF administration. 25 The notion that there is a therapeutic window based on dose and time likely explains these discrepant findings.…”

Section: Discussionmentioning

confidence: 99%

Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies

Chung

Warram²,

Day

et al. 2015

Cancer Biology & Therapy

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Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck

Abstract: Cetuximab and bevacizumab are supported by preclinical observations and are well tolerated and active in previously treated patients with SCCHN.

Cited by 128 publications

References 34 publications

Effect of selective small molecule inhibitors on MMP-9 and VEGFR-1 expression in p16-positive and -negative squamous cell carcinoma

Effect of selective small molecule inhibitors on MMP-9 and VEGFR-1 expression in p16-positive and -negative squamous cell carcinoma

Prognostic analysis of patients with locally advanced nasopharyngeal carcinoma following intensity modulated radiation therapy

Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies

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