scholarly journals Appearance of 4 Degree Rash While Treating Advanced Lung Cancer with Icotinib – Whether to Stop the Drug: A Case Report

2020 ◽  
pp. 1-4
Author(s):  
Jie Lin ◽  
Li Lv ◽  
Lifeng Jiang ◽  
Wenhui Zhang ◽  
Xinyan Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Reactions ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Advanced Lung Cancer ◽  
Epidermal Growth ◽  
Grading Standards ◽  
Skin Adnexa ◽  
Severe Adverse Reactions ◽  
Egfr Tkis

Skin and skin adnexa toxicities are the most common side effects associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Previous research showed that the rash appeared, and the severity of EGFR-TKIs may be a marker of clinical benefit. In this context, we report a 75-year-old man with advanced lung cancer who on receiving icotinib developed severe adverse reactions, 4 degree rash (NCI-CTC AE version 4.0 common toxicity grading standards grade), and refused to stop taking the drug; but with the anti-infection and symptomatic nursing, the patient recovered, the rash disappeared, and the patient received a better prognosis. Thus, we would like to emphasize the importance of deciding whether to stop the drug when patients developed adverse reactions of 3-4 degree rash.

Survival benefit of first-generation epidermal growth factor receptor–tyrosine kinase inhibitors in female with advanced lung cancer

2019 ◽  
Vol 105 (3) ◽  
pp. 216-224
Author(s):  
Byoung Soo Kwon ◽  
Ji Hyun Park ◽  
Seulgi Kim ◽  
Sojung Park ◽  
Wonjun Ji ◽  
...  
Keyword(s):  
Lung Cancer ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Advanced Lung Cancer ◽  
Group A ◽  
Epidermal Growth ◽  
Group B ◽  
Egfr Tki ◽  
Egfr Tkis

Background: This study aimed to estimate therapeutic effects of first-generation epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in real-world practice, by analyzing survival outcomes in an unselected, Korean female population with advanced lung cancer based on the National Health Insurance Service database. Methods: We identified women with newly diagnosed advanced lung cancer from January 2004 to December 2013. For progression-free survival (PFS) and overall survival (OS) analyses, patients were defined into the following subgroups: group A, treated with first-generation EGFR-TKI ⩾6 months; group B, treated with EGFR-TKIs <6 months but at least >1 month; and group C, treated with cytotoxic chemotherapy as follows: monotherapy or combination therapy with gemcitabine or pemetrexed; or monotherapy with docetaxel, paclitaxel, or vinorelbine. Results: Among 11,045 enrolled patients, 6170 (55.8%) were treated with first-generation EGFR-TKIs for at least 1 month. The median OS for patients treated with EGFR-TKIs was significantly longer than that of EGFR-TKI-naive patients (19.1 months [95% confidence interval (CI) 18.5–19.7] vs 9.5 months [95% CI 9.1–9.8], P<0.001). In subgroup analysis, group A had a significantly longer median OS compared with group B (30.3 months [95% CI 29.5–31.2] vs 12.3 months [95% CI 11.9–12.7], P<0.001). The median PFS of group A was significantly longer than that of group B (15.8 vs 3.7 months, P<0.001). Conclusions: Our analysis demonstrates that EGFR-TKIs confer significant PFS and OS benefits in the real-world practice for Korean female with advanced lung cancer.

Chitosan-derived Nanoparticles Impede Signal Transduction for T790M Lung Cancer Therapy

2021 ◽  
Author(s):  
Guojun Huang ◽  
Qi Chen ◽  
Jiawei Hu ◽  
Jianming Mao ◽  
Yunhong He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Develop Disease Progression ◽  
Lung Cancer Therapy ◽  
Epidermal Growth ◽  
Egfr Tkis ◽  
Receptor Tyrosine Kinase Inhibitors

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treated patients ultimately develop disease progression, about 50% of which involved in the emergence of a T790M mutation acquiring drug resistance. In...

scholarly journals Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhimin Zhang ◽  
Xiaojuan Lian ◽  
Wei Xie ◽  
Jin Quan ◽  
Maojun Liao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Advanced Lung Cancer ◽  
Tki Resistance ◽  
Geo Dataset ◽  
Epidermal Growth

AbstractResistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has become the main clinical challenge of advanced lung cancer. This research aimed to explore the role of PARP1-mediated autophagy in the progression of TKI therapy. PARP1-mediated autophagy was evaluated in vitro by CCK-8 assay, clonogenic assay, immunofluorescence, and western blot in the HCC-827, H1975, and H1299 cells treated with icotinib (Ico), rapamycin, and AZD2281 (olaparib) alone or in combination. Our results and GEO dataset analysis confirmed that PARP1 is expressed at lower levels in TKI-sensitive cells than in TKI-resistant cells. Low PARP1 expression and high p62 expression were associated with good outcomes among patients with NSCLC after TKI therapy. AZD2281 and a lysosomal inhibitor reversed resistance to Ico by decreasing PARP1 and LC3 in cells, but an mTOR inhibitor did not decrease Ico resistance. The combination of AZD2281 and Ico exerted a markedly enhanced antitumor effect by reducing PARP1 expression and autophagy in vivo. Knockdown of PARP1 expression reversed the resistance to TKI by the mTOR/Akt/autophagy pathway in HCC-827IR, H1975, and H1299 cells. PARP1-mediated autophagy is a key pathway for TKI resistance in NSCLC cells that participates in the resistance to TKIs. Olaparib may serve as a novel method to overcome the resistance to TKIs.

Insulin-like growth factor-1 receptor/epidermal growth factor receptor (EGFR) heterodimerization and resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13032-13032 ◽  
Author(s):  
F. Morgillo ◽  
W. K. Hong ◽  
H. Lee
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Induced Apoptosis ◽  
Egfr Tkis

13032 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been used to treat lung cancers, but resistance to these agents has been observed. This study was designed to investigate whether the insulin-like growth factor (IGF)-mediated signaling pathway induces resistance to the EGFR TKIs in lung cancer. Methods: The antitumor activities and action mechanisms of EGFR inhibitors (erlotinib, gefinitib, cetuximab), single or in combination with IGF-IR inhibitors, were assessed in vitro in a subset of non-small-cell lung cancer (NSCLC) cell lines by the MTT assay, flow cytometry-based TUNEL assay, soft agar, confocal microscopy, metabolic labeling, coimmunoprecipitation, and northern and western blot analyses, and in vivo in animal models. Correlation of EGFR and IGF-1R expression was assessed using lung tissues from patients with NSCLC. Results: EGFR TKI inhibited the proliferation and anchorage-dependent and -independent colony-forming ability of NSCLC cells, which induced apoptosis, only when IGF-1R signaling was blocked. Treatment with EGFR TKIs, but not with the EGFR antibody, induced EGFR:IGF-1R heterodimerization on cell surface and activation of the IGF-1R, resulting in the stimulation of PI3K/Akt/ mTOR pathway, promoting the de novo protein biosynthesis of survivin and EGFR, resulting in the survival of NSCLC cells. When IGF-IR and mTOR were blocked, treatment of EGFR-TKIs induced apoptosis in NSCLC cells, resulting in suppression of the NSCLC tumor growth. When we tested the expression of IGF-R and EGFR in human lung tissue, 9/14 tumor samples exhibited increased expression of EGFR and 7/9 samples showed a correlative increases in IGF-IR protein levels compared to their paired normal counterparts. Conclusions: These findings suggest that simultaneous targeting of EGFR and IGF-1R signaling pathways might be an effective therapeutic strategy against NSCLC. No significant financial relationships to disclose.

scholarly journals A Comparison Between First-, Second- and Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small-Cell Lung Cancer and Brain Metastases

2021 ◽  
Vol 2 (1) ◽  
pp. 1-10
Author(s):  
Salvatore Caponnetto ◽  
Ornella Cantale ◽  
Alex Friedlaender ◽  
Fabio Gomes ◽  
Sunil Daryanani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Egfr Tkis

Patients with non-small-cell lung cancer (NSCLC), harboring Epidermal Growth Factor Receptor (EGFR) mutations, are more susceptible to brain metastases (BM). Comparisons of the efficacy of different-generation EGFR-tyrosine kinase inhibitors (TKI) on BMs from NSCLC are currently limited. We identified studies comparing different EGFR-TKIs for NSCLC through Pubmed literature search and selected those with neurological outcome data. By two retrospective analyses, Erlotinib showed longer neurological time-to-progression (30 months vs. 15.8 months, P = 0.024) and reduced the risk of central nervous system (CNS) progression (Hazard Ratio (HR) 0.25; 95% CI, 0.08–0.81; P = 0.021) compared to Gefitinib. In a phase 2b randomized trial, 16% of patients with BMs had a similar Progression Free Survival (PFS) (HR 0.76, 95% CI 0.41–1.44) or Overall Survival (OS) (HR 1.16, 95% CI 0.61–2.21) with Afatinib versus Gefitinib; a lower risk of developing subsequent BMs with Afatinib than Gefitinib (HR 0.49; 95% CI 0.34–0.71; P < 0.001) was reported by a retrospective study. A randomized phase 3 trial proved that patients with BMs treated with Osimertinib had longer PFS (HR 0.47, 95% CI 0.30–0.74) and OS (HR 0.79, 95% CI 0.61–1.01) than with Gefitinib, and lower incidence of CNS progression (6% vs. 15%, respectively). Although there is limited evidence, differences in CNS activity may exist between EGFR-TKIs.

scholarly journals Mechanism of Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors and a Potential Treatment Strategy

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 212 ◽  
Author(s):  
Tatsuya Nagano ◽  
Motoko Tachihara ◽  
Yoshihiro Nishimura
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
T790m Mutation ◽  
Epidermal Growth ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr Tkis

Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improves the overall survival of patients with EGFR-mutated non-small-cell lung cancer (NSCLC). First-generation EGFR-TKIs (e.g., gefitinib and erlotinib) or second-generation EGFR-TKIs (e.g., afatinib and dacomitinib) are effective for the treatment of EGFR-mutated NSCLC, especially in patients with EGFR exon 19 deletions or an exon 21 L858R mutation. However, almost all cases experience disease recurrence after 1 to 2 years due to acquired resistance. The EGFR T790M mutation in exon 20 is the most frequent alteration associated with the development of acquired resistance. Osimertinib—a third-generation EGFR-TKI—targets the T790M mutation and has demonstrated high efficacy against EGFR-mutated lung cancer. However, the development of acquired resistance to third-generation EGFR-TKI, involving the cysteine residue at codon 797 mutation, has been observed. Other mechanisms of acquired resistance include the activation of alternative pathways or downstream targets and histological transformation (i.e., epithelial–mesenchymal transition or conversion to small-cell lung cancer). Furthermore, the development of primary resistance through overexpression of the hepatocyte growth factor and suppression of Bcl-2-like protein 11 expression may lead to problems. In this report, we review these mechanisms and discuss therapeutic strategies to overcome resistance to EGFR-TKIs.

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