A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma

Shek, D. W.; Longmate, Jeffrey; Quinn, David I.; Margolin, Kim; Twardowski, Przemyslaw; Gandara, David R.; Frankel, Paul; Pan, Chong Xian; Lara, Primo N.

doi:10.1007/s10147-011-0212-8

Cited by 8 publications

(3 citation statements)

References 32 publications

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“…These results are in keeping with recent IHC studies correlating EGFR overexpression and unfavorable clinico-pathological features of CCRCC, such as tumor size and SSIGN score [11], high tumor grade and stage, poorly differentiated tumors, poor prognosis [10,29,[31][32][33], invasion [30], large tumor size and shorter survival [33]. Despite the fact that anti-EGFR therapy does not appear to be effective in the absence of EGFR-related genetic anomalies [16,[34][35][36], our previous findings demonstrated the activating role of EGFR overexpression on downstream signaling pathways and its kinase-dependent function [11].…”

Section: Discussionsupporting

confidence: 87%

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma

Muroni

Ribback

Sotgiu

et al. 2021

IJMS

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EGFR is overexpressed in the majority of clear cell renal cell carcinomas (CCRCCs). Although EGFR deregulation was found to be of great significance in CCRCC biology, the EGFR overexpression is not associated with EGFR-targeted therapy responsiveness. Moreover, the prognostic role of EGFR expression remains controversial. In the present study, we evaluated the role played by EGFR overexpression in CCRCC and its prognostic significance associated with different immunohistochemical localization patterns. In our study, the Total Score (TS) related to membranous-cytoplasmic EGFR expression showed a significant correlation with grade, pathologic stage (pT), and Stage, Size, Grade, and Necrosis (SSIGN) score, and a negative correlation with nuclear EGFR expression. No significant correlations were shown between nuclear EGFR and clinic-pathological features. Additionally, a correlation between SGLT1 expression levels and pT was described. Multivariate analysis identifies pT and SSIGN score as independent prognostic factors for CCRCC. A significantly increased survival rate was found in the case of positive expression of nuclear EGFR and SGLT1. Based on our findings, SGLT1 and nuclear EGFR overexpression defines a subgroup of CCRCC patients with good prognosis. Membranous-cytoplasmic EGFR expression was shown to be a poor prognostic factor and could define a CCRCC subgroup with poor prognosis that should be responsive to anti-EGFR therapies.

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Section: Discussionsupporting

confidence: 87%

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma

Muroni

Ribback

Sotgiu

et al. 2021

IJMS

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“…It is clear that the occurrence of EGFR-TKIs sensitive mutation in non-adenocarcinoma was relatively rare. In addition, a previous study reported that the patients who expressed sensitive mutations in non-adenocarcinoma responded poorly and non-effectively to the EGFR-TKIs [29], and hence whether it is even a necessity to undergo a routine mutation test in the absence of adenocarcinomas. However, in the study of Chiu and coworkers, they pointed out that it is useful to have an EGFR mutation test for those patients who have a poor performance status or other comorbidities [30].…”

Section: Discussionmentioning

confidence: 99%

An Analysis of EGFR Mutations among 1506 Cases of Non-Small Cell Lung Cancer Patients in Guangxi, China

et al. 2016

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An association between epidermal growth factor receptor (EGFR) and clinical characteristics of non-small cell lung cancer (NSCLC) was reported ten years ago. In addition, a different type of relationship was seen in different ethic races. However, the relationship between these factors is not well understood in the Guangxi province. Up to now, there are only very limited data on the association of TTF1/EGFR protein positivity and EGFR mutation status in NSCLC. This study aims to investigate the role of EGFR gene mutation status on the clinical characteristics and the relationship with TTF-1/EGFR protein positivity of patients with NSCLC in Guangxi, China. 1506 samples from different patients with NSCLC were detected by amplification refractory mutation system for 29 hotspot mutations. Analysis of the relationship between clinical characteristics and EGFR mutation status was performed by using the crosstabs Chi-square and SPSS 21.0 software. Of 1506 samples, 537 (35.7%) revealed tyrosine kinase inhibitor (TKI) sensitive EGFR mutations with 27 (1.8%) cases harboring TKI resistant EGFR mutations or union co-existing EGFR-TKIs sensitive mutations. EGFR-TKIs sensitive mutations were not significantly associated with age and TNM-M stage (P = 0.863; P = 0.572, respectively). However, they were significantly associated with p-stage, TNM-T stage and TNM-N stage (P = 0.011, P < 0.001, P = 0.036, respectively). Immunohistochemical studies revealed that TTF-1 and EGFR protein expression level were all associated with EGFR mutation status (P < 0.001, P = 0.002, respectively). Of the 537 EGFR-TKIs sensitive mutation cases, the rates of exon 19-del, 18 G719X point, exon 21 L858R and L861Q points were 54.6, 0.9, 42.3 and 0.9%, respectively. EGFR TKI-sensitive mutations commonly occur in female, non-smoking and adenocarcinoma patients. The p-stage, TNM-T stage, TNM-N stage, EGFR and TTF-1 protein expression levels have close relationships with EGFR mutation status.

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“…Treatment was generally well tolerated. Furthermore, gefitinib was also evaluated in combination with pegylated IFN α , without obtaining significant results [36]. …”

Section: Tyrosine Kinase Inhibitors “Enlarged” Familymentioning

confidence: 99%

Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

Conti

Santoni²,

Amantini³

et al. 2013

BioMed Research International

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Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents.

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A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma

Cited by 8 publications

References 32 publications

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma

An Analysis of EGFR Mutations among 1506 Cases of Non-Small Cell Lung Cancer Patients in Guangxi, China

Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

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