Gefitinib with pemetrexed as first-line therapy in patients with advanced nonsquamous non-small cell lung cancer with activating epidermal growth factor receptor mutations

Yoon, Shinkyo; Lee, Dong Hoon

doi:10.21037/atm.2016.12.64

Cited by 3 publications

(2 citation statements)

References 20 publications

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“…In this regard, it still remains an open question. In addition, some research found that EGFR-TKI plus chemotherapy could not only improve the antitumor effect, but could also delay and prevent the appearance of gefitinib-resistance clones (28,29). This therapy may overcome the heterogeneity in the resistance to gefitinib (30).…”

Section: Discussionmentioning

confidence: 99%

A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation

et al. 2018

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The discovery of epidermal growth factor receptor (EGFR)‑sensitive mutations in non‑small cell lung cancer (NSCLC) and the successful clinical application of EGFR tyrosine kinase inhibitors (TKIs) have changed the regimen of lung cancer therapy from traditional cytotoxic chemotherapy to molecular‑targeted cancer therapy. However, the main limitation of EGFR‑TKI therapy is the heterogeneity of lung cancer harboring EGFR‑sensitive mutations. In addition, the synergistic effect of the administration of chemotherapy and EGFR‑TKIs, combined with tumor heterogeneity, on NSCLC remains unclear. The present study aimed to investigate the optimal schedule for combined treatment with paclitaxel/gemcitabine and gefitinib in co‑cultured NSCLC cell lines, in which PC9 cells were mixed with A549 cells at 0:1, 1:19, 1:3, 1:1, 3:1 and 1:0 ratios, and clarified the associated mechanisms. The mixed cells were used to simulate the tumor heterogeneity in the human cancer environment and to define the differential anti‑proliferative effects of nine schedules of paclitaxel/gemcitabine and gefitinib, based on cell cycle distribution. We confirmed that gefitinib arrested PC9 cell growth, mainly at the G1 phase, at 24 h regardless of low or high concentration. After a 24‑h culture in gefitinib‑free medium, the cell cycle returned to its normal state. Paclitaxel and gemcitabine induced G2/M phase and S phase arrest at 72 h, respectively. The anti‑proliferative effect of paclitaxel/gemcitabine followed by gefitinib resulted in the optimum anti‑proliferative activity compared with the other seven schedules, which was not affected by tumor heterogeneity. Cell cycle‑dependent synergism may contribute to this effect. Our results are in accordance with most of the existing clinical trials, and could provide a potential treatment option for patients with advanced NSCLC and for the ongoing clinical investigation of the sequential treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation

et al. 2018

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“…Several randomized clinical studies have also reported on the increased effectiveness of combined chemotherapy/ EGFR TKI treatments in patients with NSCLC bearing an EGFR mutation. Therefore, to prevent or delay the emergence of acquired resistance to EGFR TKIs, adding carboplatin and pemetrexed to gefitinib is recommended as a first-line option in patients with EGFR-mutated tumors [35][36][37][38][39][40].…”

Section: Target Independentmentioning

confidence: 99%

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

Gorachinov¹,

Mraiche²,

Moustafa³

et al. 2023

Beilstein J. Nanotechnol.

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Genomic and proteomic mutation analysis is the standard of care for selecting candidates for therapies with tyrosine kinase inhibitors against the human epidermal growth factor receptor (EGFR TKI therapies) and further monitoring cancer treatment efficacy and cancer development. Acquired resistance due to various genetic aberrations is an unavoidable problem during EGFR TKI therapy, leading to the rapid exhaustion of standard molecularly targeted therapeutic options against mutant variants. Attacking multiple molecular targets within one or several signaling pathways by co-delivery of multiple agents is a viable strategy for overcoming and preventing resistance to EGFR TKIs. However, because of the difference in pharmacokinetics among agents, combined therapies may not effectively reach their targets. The obstacles regarding the simultaneous co-delivery of therapeutic agents at the site of action can be overcome using nanomedicine as a platform and nanotools as delivery agents. Precision oncology research to identify targetable biomarkers and optimize tumor homing agents, hand in hand with designing multifunctional and multistage nanocarriers that respond to the inherent heterogeneity of the tumors, may resolve the challenges of inadequate tumor localization, improve intracellular internalization, and bring advantages over conventional nanocarriers.

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Dietary determinants of overnutrition among hypertensive patients in southwest Ethiopia: an ordinal regression model

Gebre,

Alemayehu Beyene,

Muktar

et al. 2024

Sci Rep

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Overnutrition is a recognized risk factor for hypertension, but evidence is lacking among hypertensive patients for tailored dietary interventions. This study assessed dietary factors in 331 hypertensive patients in southwest Ethiopia. The data was collected through a questionnaire and analyzed using factor analysis. Body mass index (BMI) was calculated, and a BMI above 25 kg m−2 was considered overnutrition. An ordinal logistic regression model was used to model the data and control confounders. Adjusted odds ratio and p-values were reported. Among the 331 respondents, consumption of cereals and grains (57.0%); roots and tubers (58.5); and legumes (50.0%), while 28.6% drink alcohol, was common. About 29.0% (24.1–34.2) had overnutrition (22%, 17.6–26.6%, overweight and 7.0%, 4.5–10.3%, obesity). While the predicted odds of overnutrition were higher among males (AOR = 2.85; 1.35–6.02), married (AOR = 1.47; 0.69–3.12), illiterates (AOR = 2.09; 1.18–3.72), advanced age (AOR = 1.65; 0.61–4.61), government employees (AOR = 6.83; 1.19–39.2), and urban dwellers (AOR = 4.06; 1.76–9.36), infrequent vegetable consumption (AOR = 1.47; 0.72–2.96) and lower and higher terciles of cereals and animal-source food consumption (AOR = 1.56; 0.72–3.34). Overnutrition among hypertensive patients was significantly high and associated with unhealthy dietary consumption, educational status, residence, and occupation, emphasizing the need for targeted dietary counseling.

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Gefitinib with pemetrexed as first-line therapy in patients with advanced nonsquamous non-small cell lung cancer with activating epidermal growth factor receptor mutations

Cited by 3 publications

References 20 publications

A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation

A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

Dietary determinants of overnutrition among hypertensive patients in southwest Ethiopia: an ordinal regression model

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