The expression of p53, c-erbB-1 and c-erbB-2 molecules and their correlation with prognostic markers in patients with head and neck tumors

Khademi, Bijan; Shirazi, Farzaneh Mohammadalizadeh; Vasei, Mohammad; Doroudchi, Mehrnoosh; Gandomi, B.; Modjtahedi, Helmout; Pezeshki, Abdul Mohammad; Ghaderi, Abbas

doi:10.1016/s0304-3835(02)00242-2

Cited by 66 publications

(57 citation statements)

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“…The tumors of only two patients in this study overexpressed HER2 and even in these two patients, neither experienced a response. Data published subsequent to the design and conduct of this study have shown substantially lower rates of HER2 overexpression in SCCHN [7,12,13] and the results of other clinical studies of dual EGFR and HER2 inhibitors have not improved survival [14,15]. Although recently published preclinical data suggest that lapatinib is more active against HPV-driven disease [16], our small p16+ subgroup data cannot add clinical support to this finding.…”

Section: Accepted Articlementioning

confidence: 70%

“…Recently presented data indicate excellent tolerability and efficacy as a single agent in the second line setting in head and neck cancer; in a phase II study of capecitabine 1250mg/m 2 BID, mOS was 7.1 months and PFS 4.8 months, with minimal toxicity. [14] Further, in an era of increasingly popular use of induction chemotherapy and chemoradiotherapy, the metastatic patient has often Version 3/8/2011…”

Section: Capecitabinementioning

confidence: 99%

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Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Weiss

Bagley

Hwang

et al. 2016

Cancer

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Funding: GSK (subsequently Novartis) funded this study. There are no NIH grants related to this work.COI: RBC has served as a consultant to GSK. CJL has served as a consultant to Novartis. The remaining authors report no COIs directly related to this work. Précis:Patients with first line recurrent/metastatic head and neck cancer were treated with the all-oral regimen capecitabine and lapatinib. mPFS was 4.2 months and mOS was 10.7 months. Keywords: head and neck neoplasms, capecitabine, lapatinib Page 2 of 72 CancerThis article is protected by copyright. All rights reserved. Accepted Article Abstract:Background: Combination of cisplatin, 5FU and cetuximab is a standard treatment for recurrent/metastatic head and neck cancer with a high rate of toxicity.Identifying less toxic, equally effective regimens is imperative. We therefore investigated first-line treatment with an all-oral regimen of capecitabine and lapatinib.Materials and Methods: Patients were required to have incurable head and neck cancer of any primary site other than nasopharynx, PS0-2, and no prior exposure to capecitabine or lapatinib. Subjects were treated with capecitabine 1000mg/m 2 BID and lapatinib 1250mg daily. Capecitabine was administered for 14 of 21 days for 4 cycles. Lapatinib was administered daily until progression. The primary outcome was overall survival (OS).Results: 44 subjects were accrued between 11/13/2009 and 4/29/2014. Patients with PS0 were 38.6% of the sample, PS1 52.3%, and PS2 9.1%. 81.8% were male and the median age was 62 years. Prior attempts at curative treatment with chemotherapy had been utilized in 68.2% of patients (platinum used in 55.8%).There was no grade 5 toxicity. The most common adverse events were diarrhea (18.2% G3) and rash (13.6% G3). The primary objective was met; OS was 10.7 months (90% CI 8.7 to 12.9). Overall response rate was 25% (90% CI: 15%-38%).PFS was 4.2 months (90% CI 3.6 to 5.1). Results were not substantially different when subdivided by p16 status. Only two patients were positive for HER2 by IHC.Conclusions: The study met its primary objective of survival comparable to the EXTREME regimen and toxicity of this all-oral regimen was tolerable. Page 3 of 72 CancerThis article is protected by copyright. All rights reserved. Accepted Article Introduction:Recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) remains incurable in the vast majority of cases. Cisplatin-containing regimens have been the standard treatment platform for more than 2 decades. The most recent advance was the addition of cetuximab to a cis-or carboplatin-containing regimen, which increased overall survival from 7.4 to 10.1 months compared to chemotherapy alone [1]. The EXTREME regimen represented the first significant breakthrough in the treatment of R/M HNSCC, but it came at a price. Adverse events in both arms of the EXTREME trial were significant; 76% of patients receiving 5FU and platinum experienced grade 3-4 adverse events, and 82% of patients receiving cisplatin, 5FU, and cetuximab experienced grade 3...

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Section: Accepted Articlementioning

confidence: 70%

Section: Capecitabinementioning

confidence: 99%

Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Weiss

Bagley

Hwang

et al. 2016

Cancer

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“…In various studies purely membranous (Craven et al, 1992;Hoffmann et al, 2001;Khademi et al, 2002;Kuropkat, 2002) or cytoplasmic (Craven et al, 1992;Field et al, 1992;Angiero et al, 2008;Khademi et al, 2002), and mixed membranous-cytoplasmic (Kearsley et al, 1991;Craven et al, 1992;Xia et al, 1997;Ibrahim et al, 1997;Xia et al, 1999;Bei et al, 2004;Rautava et al, 2008) expression have been reported.…”

Section: Discussionmentioning

confidence: 99%

HER2/neu Expression in Head and Neck Squamous Cell Carcinoma Patients is not Significantly Elevated

Sardari¹,

Pardis²,

Andisheh-Tadbir³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: HER2/neu, a member of EGFR family, is over expressed in some tumors .The purpose of this study was to determine the salivary level and tissue expression of HER2/neu in patients with head and neck squamous cell carcinoma (HNSCC) and any correlation with clinicopathologic parameters. Methods: An enzymelinked immunosorbent assay (ELISA) was used to evaluate the salivary level and immunohistochemistry (IHC) to assess tissue expression of HER2/neu in 28 patients with HNSCC and 25 healthy controls. Results: The salivary levels of HER2/neu in HNSCC patients was not significantly higher than in the healthy controls (p>0.005). There was no apparent correlation in salivary HER2/neu level with clinicopathological features such as age, sex, grade, tumor size and nodal status. All HNSCC specimens were positive (membranous or/and cytoplasmic) for HER2/ neu, except one sample. Only one HNSCC specimen was stained in cytoplasm purely. All control specimens were membranous and cytoplasmic positive for HER2/neu. There was a significant difference between cytoplasmic staining in case and control groups (p-value<0.05). Conclusion: In our cases, no overexpression of HER2/neu was observed. Thus, our findings suggested that the use of Her-2 as a salivary marker of HNSCC cannot be recommended.

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“…HER-2 appears to function primarily as a heterodimerization partner for other HER family members (12). HER-2 overexpression has been observed in HNSCC (13) and heterodimerization of HER-2 and EGFR is thought to mediate disease progression (14). High expression of EGFR and/or HER-2 has been associated with tumor cell resistance to chemotherapy and radiotherapy (14,15).…”

Section: Introductionmentioning

confidence: 99%

Combined molecular targeted drug therapy for EGFR and HER-2 in head and neck squamous cell carcinoma cell lines

et al. 2012

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Abstract. The epidermal growth factor receptor (EGFR) and related family member, HER-2, are often overexpressed simultaneously in patients with a variety of malignant tumors, and the combination may cooperatively promote cancer cell growth and survival. The purpose of this study was to examine antitumor effects of the combination treatment of cetuximab and trastuzumab on head and neck squamous cell carcinoma (HNSCC) using 16 HNSCC cell lines in terms of antiproliferative effect and antibody-dependent cell-mediated-cytotoxicity (ADCC). Previously we have reported the expression levels of EGFR mRNA on 16 HNSCC cell lines. All cell lines expressed mRNA for EGFR, HER-2 and HER-3; 12 cell lines expressed mRNA for HER-4; and 4 cell lines did not express mRNA for HER-4. In in vitro proliferation assay, the combin ation treatment of cetuximab and trastuzumab significantly lowered cell viability compared to either drug alone. The mRNA expression levels of EGFR and HER-2 were not correlated with the efficacy of the combination treatment of cetuximab and trastuzumab and the expression levels of HER-3 and HER-4 also showed no correlation with the efficacy of the combination treatment. We evaluated the gene status of HER-2 exons 23 and 24 in 16 HNSCC cell lines, but there was no mutation of HER-2 in any of the cell lines. Either drug showed ADCC in the 3 cell lines using peripheral blood mononuclear cells (PBMCs), however, a significant combination effect was not observed. Combined molecular targeted antibody drug therapy for EGFR and HER-2 may be useful in the treatment of HNSCC. IntroductionHead and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer and 500,000-900,000 HNSCC cases are newly diagnosed annually worldwide (1). The standard treatments for advanced HNSCC include surgery, radiotherapy and chemotherapy. These treatment modalities prolong the survival of individuals with advanced stage HNSCC; however, the treatment benefit is typically temporary in advanced-stage disease (2). Thus, novel and effective antitumor therapies, e.g., targeted molecular therapy, immunotherapy and gene therapy, are necessary for treating advanced HNSCC. Several new molecular-targeted drugs have been studied recently for HNSCC treatment and promising results have been obtained (3-8).The epidermal growth factor receptor (EGFR) belongs to the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases; this family includes EGFR (ErbB1 or HER-1), HER-2 (ErbB2), HER-3 (ErbB3) and HER-4 (ErbB4). EGFR overexpression has been frequently observed in HNSCC and is thought to be associated with carcinogenesis, metastasis, clinical stage of cancer, and poor prognosis (9,10). HER-2 is a unique receptor since none of the known HER family ligands activate HER-2 homodimers (11). HER-2 appears to function primarily as a heterodimerization partner for other HER family members (12). HER-2 overexpression has been observed in HNSCC (13) and heterodimerization of HER-2 and EGFR is thought to mediate disease progression (14...

show abstract

The expression of p53, c-erbB-1 and c-erbB-2 molecules and their correlation with prognostic markers in patients with head and neck tumors

Cited by 66 publications

References 28 publications

Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

HER2/neu Expression in Head and Neck Squamous Cell Carcinoma Patients is not Significantly Elevated

Combined molecular targeted drug therapy for EGFR and HER-2 in head and neck squamous cell carcinoma cell lines

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