Gefitinib for advanced non-small cell lung cancer

Sim, Esther; Yang, Ian A.; Fong, Kwun M.; Wood‐Baker, Richard; Bowman, Rayleen V.

doi:10.1002/14651858.cd006847

Cited by 11 publications

(8 citation statements)

References 5 publications

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“…Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including gefitinib, display dramatic therapeutic efficacy in non-small cell lung cancer patients that have EGFR-activating mutations, and are recommended as the standard first-line therapy in non-small cell lung cancer [1]. However, despite excellent clinical responses, this drug might promote severe and lethal interstitial lung disease (ILD) that restricts the therapeutic efficacy of this agent.…”

Section: Introductionmentioning

confidence: 99%

Molecular hydrogen attenuates gefitinib-induced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress and inflammation

Terasaki

Suzuki

Tonaki

et al. 2019

Laboratory Investigation

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Although inhibition of epidermal growth factor receptor (EGFR)-mediated cell signaling by the EGFR tyrosine kinase inhibitor gefitinib is highly effective against advanced non-small cell lung cancer, this drug might promote severe acute interstitial pneumonia. We previously reported that molecular hydrogen (H 2) acts as a therapeutic and preventive antioxidant. Here, we show that treatment with H 2 effectively protects the lungs of mice from severe damage caused by oral administration of gefitinib after intraperitoneal injection of naphthalene, the toxicity of which is related to oxidative stress. Drinking H 2 −rich water ad libitum mitigated naphthalene/gefitinib-induced weight loss and significantly improved survival, which was associated with a decrease in lung inflammation and inflammatory cytokines in the bronchoalveolar lavage fluid. Naphthalene decreased glutathione in the lung, increased malondialdehyde in the plasma, and increased 4-hydroxy-2nonenal production in airway cells, all of which were mitigated by H 2-rich water, indicating that the H 2-rich water reverses cellular damage to the bronchial wall caused by oxidative stress. Finally, treatment with H 2 did not interfere with the antitumor effects of gefitinib on a lung cancer cell line in vitro or on tumor-bearing mice in vivo. These results indicate that H 2rich water has the potential to improve quality of life during gefitinib therapy by mitigating lung injury without impairing anti-tumor activity.

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Section: Introductionmentioning

confidence: 99%

Molecular hydrogen attenuates gefitinib-induced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress and inflammation

Terasaki

Suzuki

Tonaki

et al. 2019

Laboratory Investigation

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“…Because it usually interferes with specific proteins involved in tumor genesis only, it does not have as many severe side effects as conventional chemotherapy. [25][26][27] Older patients receiving TT are better able to maintain their usual daily activities because it slows down the deterioration of health and frailty and improves their quality of life, meaning they probably retain their autonomy. 28 There are various targeted therapy agents available for the treatment of mNSCLC.…”

Section: Discussionmentioning

confidence: 99%

<p>Survival Analysis of Antineoplastic Treatment for Older Patients with Metastatic Non-Small-Cell Lung Cancer: A Clinical Database Study</p>

Yu¹,

Cheng²,

Chen³

et al. 2020

CMAR

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Purpose To explore whether antineoplastic treatment can improve overall survival (OS) in older patients with metastatic non-small-cell lung cancer (mNSCLC). Patients and Methods Using the cancer registry database of a tertiary medical center in Taiwan, we followed patients 65 years old and above with pathologically proved mNSCLC. Chi-square test and Cox regression were used to analyze differences in clinical characteristics, the treatments they received, and factors predicting survival. Kaplan–Meier survival analysis was used to analyze OS differences. Results A total of 542 older patients were diagnosed with mNSCLC from 2011 to 2017. Multivariate Cox regression showed that patients receiving targeted therapy (TT) alone, chemotherapy (CT) alone, and crossover (CO) treatment were at significantly less risk of short OS [hazard ratio (HR) 0.351, 95% confidence interval (CI), 0.257–0.479; HR 0.517, CI 0.376–0.711; and HR 0.544, CI 0.373–0.792, respectively]. Patients at significantly increased risk of short OS were those aged ≥85 years and those assigned poorer Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores (HR 1.513, CI 1.135–2.017, and HR 2.854, CI 2.188–3.724, respectively). The result of Kaplan–Meier survival analysis of 418 patients with ECOG-PS scores 0–2 suggested that patients who received antineoplastic treatments had a significantly better median OS than those receiving supportive care (SC), those receiving TT having the best result (SC, 4.00 months; TT, 21.17 months; CT, 12.83 months; CO, 15.83 months, P<0.001). Conclusion Antineoplastic treatments, especially TT, can improve OS for selected older patients with mNSCLC.

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“…Gefitinib is a small molecule inhibitor of EGFR tyrosine kinase, and it can inhibit receptor phosphorylation and block the subsequent activation of EGFR-mediated signaling pathways [7]. Gefitinib has been applied for clinical application in non-small cell lung cancer (NSCLC), and exhibited antiproliferative and anti-invasive effects in glioblastoma in vitro [8][9][10]. However, gliomas were refractory to TKI and EGFR-associated TKI only showed marginal benefits in recurrent malignant gliomas [11].…”

Section: Introductionmentioning

confidence: 99%

MiR-450a-5p strengthens the drug sensitivity of gefitinib in glioma chemotherapy via regulating autophagy by targeting EGFR

et al. 2020

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Glioma reported to be refractory to EGFR tyrosine kinase inhibitor is the most common malignant tumor in central nervous system. Our research showed the low expression of miR-450a-5p and high expression of EGFR in glioma tissues. MiR-450a-5p was also observed to synergize with gefitinib to inhibit the proliferation, migration and invasion and induce the apoptosis and autophagy of glioma cells. Furthermore, miR-450a-5p was demonstrated to target 3′UTR of EGFR, and regulated EGFR-induced PI3K/AKT/mTOR signaling pathway. Moreover, the above effects induced by miR-450a-5p in glioma cells were reversed by WIPI1 silencing. The inhibition role of miR-450a-5p on glioma growth was also confirmed in vivo by subcutaneous and intracranial tumor xenografts. Therefore, we conclude that miR-450a-5p synergizes with gefitinib to inhibit the glioma tumorigenesis through inducing autophagy by regulating the EGFR-induced PI3K/AKT/mTOR signaling pathway, thereby enhancing the drug sensitivity of gefitinib.

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Gefitinib for advanced non-small cell lung cancer

Cited by 11 publications

References 5 publications

Molecular hydrogen attenuates gefitinib-induced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress and inflammation

Molecular hydrogen attenuates gefitinib-induced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress and inflammation

<p>Survival Analysis of Antineoplastic Treatment for Older Patients with Metastatic Non-Small-Cell Lung Cancer: A Clinical Database Study</p>

MiR-450a-5p strengthens the drug sensitivity of gefitinib in glioma chemotherapy via regulating autophagy by targeting EGFR

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