Objective To systematically review the effectiveness and safety of erlotinib for the elderly with Non-small-cell lung cancer (NSCLC). Methods Databases including The Cochrane Library, PubMed, EMbase, CBM, VIP, CNKI and WanFang Data were electronically searched for relevant randomized controlled trails (RCTs). Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.0 software. Results Totally 5 studies were included. The results of meta-analysis showed that, the objective response rate and stable disease rate was similar between the erlotinib group and the control group with no significant difference (RR=0.99, 95%CI 0.34 to 2.93, P=0.99; RR=1.17, 95%CI 0.95 to 1.43, P=0.14). The incidences of Grade Ⅲ-Ⅳ neutropenia and thrombocytopenia were lower in the erlotinib group than those in the control group (OR=0.12, 95%CI 0.03 to 0.52, P=0.005; OR=0.19, 95%CI 0.04 to 0.91, P=0.04); and the incidences of nausea and vomiting as wel as liver impairments were alike between the two groups (OR=0.93, 95%CI 0.12 to 7.08, P=0.95; OR=0.80, 95%CI 0.24 to 2.68, P=0.71); the incidences of diarrhea and skin rashes in the erlotinib group were higher (OR=5.96, 95%CI 1.28 to 27.88, P=0.02; OR=6.77, 95%CI 1.52 to 30.10, P=0.01). Conclusion Current evidence shows that, erlotinib is effective and safe in treating the elderly with NSCLC with better effects and no serious adverse reaction. However, due to the limited quantity and quality of the included studies, more high quality studies with large sample size and long-term follow-up are still needed to verify the above conclusion.
Objective To evaluate the effects of two different epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs) , Gefitinib and Erlotinib, on lung fibrosis induced by bleomycin.Methods Forty BALB/c female mice were randomly divided into four groups, ie. a control group( saline given orally and intratracheally) , a fibrosis group( saline given orally with bleomycin instillation) , a Gefitnib group( Gefitnib 20 mg/kg given orally with bleomycin instillation) , and an Erlotinib group ( Erlotinib25 mg/kg given orally with bleomycin instillation) . Bleomycin ( 3 mg/kg) was intratracheally instilled on the first day. Gefitinib or Erlotinib was given orally daily and normal saline as control. Then they were sacrificed by abdominal aortic bleeding 14 days after the bleomycin instillation. The left lung was stained with HE and Masson’s trichrome staining respectively for pathological examination. Total EGFR and phosphorylated EGFR were detected by immunohistochemistry. Hydroxyproline ( HYP) assay was performed in the right lung.Results Both Gefitinib and Erlotinib significantly reduced lung collagen accumulation and the content of HYP. Immunohistochemistry revealed that phosphorylation of EGFR in lung mesenchymal cells induced by bleomycin was inhibited. Furthermore, there was no difference between Gefitinib and Erlotinib in inhibiting lung fibrosis. Conclusion Our findings suggest that, in the preclinical setting, EGFR-TKIs may have aprotective effect on lung fibrosis induced by bleomycin.
ObjectiveTo improve the knowledge of erlotinib-induced severe rash and fatal interstitial lung disease (ILD). MethodsThe clinical feature and radiology of erlotinib-associated severe rash and fatal ILD were analyzed in one patient with advanced non-small cell lung cancer (NSCLC) in the 81st Hospital of Chinese PLA,and the related literatures were reviewed. ResultsThe patient was a 78-year-old male non-smoker with stage Ⅳ right lower lobe squamous cell carcinoma,and his epidermal growth factor receptor gene showed mutation at exon 21.He had a history of chronic obstructive pulmonary disease and mild pulmonary fibrosis.Following one cycle of chemotherapy with gemcitabine plus cisplatin,he received erlotinib 150 mg daily.After 40 days of targeting therapy,the size of the lung cancer was decreased significantly concomitant with severe rash.Again,severe rash and fatal ILD appeared after using erlotinib 100 mg daily for 4 days and 50 mg daily for 2 days,respectively.The tumor progressed markedly although both rash and ILD were almost abolished following withdrawal of erlotinib as well as empirical impact of glucocorticoid and sequential therapy. ConclusionPhysicians should be alerted to the possibility of erlotinib-induced severe rash and fatal ILD.Those with pathologic findings of usual interstitial pneumonia on resected lung specimens or known pulmonary fibrosis may be at particular risk for erlotinib-related pulmonary toxicity.
ObjectivesTo systematically review the efficacy and safety of the first generation EGFR-TKIs versus pemetrexed as second-line treatment for advanced non-small cell lung cancer (NSCLC).MethodsDatabases including PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and CBM were searched to collect randomized controlled trials (RCTs) about the first generation EGFR-TKIs versus pemetrexed as second-line treatment for advanced NSCLC from inception to June 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 20 RCTs involving 2 242 patients were finally included. The results of meta-analysis showed that: the rate of progression free survival (PFS) in the EGFR-TKI group was superior to the pemetrexed group (HR=0.78, 95%CI 0.58 to 0.99, P<0.000 1) with significant difference. However, there was no significant difference between two groups in complete remission rate (RR=1.81, 95%CI 0.65 to 5.07,P=0.26), partial remission rate (RR=0.93, 95%CI 0.78 to 1.11, P=0.44), stable disease rate (RR=0.92, 95%CI 0.82 to 1.03, P=0.16), progression disease rate (RR=1.09, 95%CI 0.99 to 1.20, P=0.09), overall response rate (RR=0.97, 95%CI 0.72 to 1.30, P=0.84), disease control rate (RR=0.93, 95%CI 0.87 to 1.01, P=0.07) and overall survival rate (HR=0.89, 95%CI 0.74 to 1.04, P<0.572). The incidences of skin rash (RR=12.43, 95%CI 3.98 to 38.84,P<0.01) and diarrhea (RR=3.94, 95%CI 2.32 to 6.70,P<0.01) were significantly higher in the EGFR-TKI group, but the incidences of leukopenia (RR=0.19, 95%CI 0.09 to 0.41,P<0.01 ), anemia (RR=0.40, 95%CI 0.17 to 0.92,P=0.03), thrombocytopenia (RR=0.37, 95%CI 0.14 to 0.97, P=0.04), nausea and vomiting (RR=0.50, 95%CI 0.28 to 0.87, P=0.01), constipation (RR=0.30, 95%CI 0.14 to 0.64, P=0.002) were significant lower in the EGFR-TKI group than that of the pemetrexed group.ConclusionGefitinib shows some superiority to pemetrexed in second-line treatment for NSCLC, and it can be used as the second-line drug for advanced NSCLC. Due to the limited quality and quantity of included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo study effects of two kinds of epidermal growth factor receptor kinase inhibitors on bleomycin-induced pulmonary fibrosis in mice, and regulation mechanism on oncostatin M (OSM) and downstream signaling pathways.MethodsForty Kunming female mice were randomly divided into a control group, a fibrosis group, a gefitinib group, and an erlotinib group. The mice in the control group were administered with saline aerosol intratracheally. The mice in the fibrosis group were administered with bleomycin at a dose of 3 mg/kg aerosol intratracheally. The mice in the gefitinib group and the erlotinib group were administered with bleomycin at a dose of 3 mg/kg aerosol intratracheally and then gastrically perfused with gefitinib (20 mg·kg–1·d–1) or erlotinib (25 mg·kg–1·d–1). All mice accepted computer tomography examination 14 days after the treatment and then were sacrificed, and the lungs were collected for further detection. The lungs were stained with hematoxylin eosin and Masson’s trichrome, examined with Western blot for pathological examination and expressions of α-smooth muscle actin (α-SMA), OSM, Janus kinase 1 (JAK1), phospho-JAK1 (p-JAK1), signal transducers and activators of transcription 3 (STAT3), and phospho-STAT3 (p-STAT3) proteins.ResultsThe pathological injury of the lung in the gefitinib group and the erlotinib group was significantly relieved compared with that in the bleomycin group. The expressions of α-SMA, OSM, p-JAK1/JAK1, and p-STAT3/STAT3 proteins were also significantly reduced. There were no differences between the above-mentioned indexes between the gefitinib group and the erlotinib group.ConclusionsGefitinib and erlotinib can significantly relieve bleomycin-induced pulmonary fibrosis in mice. The underlying mechanism may be involved in inhibiting expression of OSM and downstream JAK/STAT pathways.