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.
Objective To systematically review the cost-effectiveness of gefitinib for advanced non-small cell lung cancer (NSCLC), in order to provide the economics values of gefitinib for clinical application. Method We electronically searched databases including PubMed, Ovid, Embase, Cochrane Library, Medline, China National Knowledge Internet, VIP, and Wanfang database for articles about the cost-effectiveness of gefitinib for advanced NSCLC patients from January 1946 to October 2017, and then performed a systematic literature review of economic evaluations of geftinib. Results A total of 20 independent studies were included in the present systematic review, in which 8 were the first-line treatment, 9 were the second-line treatment, 1 was the third-line treatment, and 2 were maintenance treatment. The most common comparison was gefitinib vs. chemotherapy (n=7), and other comparisons were gefitinib vs. erlotinib (n=4), gefitinib vs. docetaxel (n=3), gefitinib vs. placebo (n=2), gefitinib vs. icotinib (n=2), gefitinib vs. afatinib (n=1), and gefitinib vs. other treatments (n=1). For the advanced NSCLC patients, the first- or second-line treatment with gefitinib compared to chemotherapy was considered to be more cost-effective, especially in patients with mutated epidermal growth factor receptor gene. As the second-line treatment, gefitinib was considered to be more economical than erlotinib and docetaxel. Conclusion Gefitinib is considered to be a cost-effective strategy for the advanced NSCLC patients as the first- or second-line therapy.
ObjectiveBy intervening with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, to explore the downstream signaling pathway of the transcription factor forkhead box O3a (Foxo3a) in C57BL/6 mice who are induced to pulmonary fibrosis with bleomycin, as so to illuminate the possible mechanism of Foxo3a in epithelial-mesenchymal transition (EMT) of pulmonary fibrosis.MethodsThirty C57BL/6 mice aged 6 weeks in half genders were randomly divided into a control group, a bleomycin group and a gefitinib group. The mice in the control group were injected with saline via trachea. The mice in the bleomycin group were injected with bleomycin at a dose of 3 mg/kg via trachea. The mice in the gefitinib group were injected with bleomycin at a dose of 3 mg/kg via trachea and then gastrically perfused with gefitinib (20 mg·kg–1·d–1). 14 days after the treatment, all mice were killed and lung tissue specimens were collected for further detection. Lung tissue sections were stained with hematoxylin eosin and Masson’s trichrome. The mRNA levels of α-smooth muscle actin (α-SMA), E-cadherin, high mobility group protein box 1 (HMGB1), Foxo3a, FoxM1 and Snail1 in the lung tissues were detected by RT-PCR. The protein expressions of α-SMA, E-cadherin, HMGB1, phospho-Foxo3a (p-Foxo3a), Foxo3a, FoxM1 and Snail1 in the lung tissues were determined by western blot.ResultsThe scores of lung inflammation and fibrosis were evidently decreased in the gefitinib group compared with that in the bleomycin group (P<0.01). Compared with bleomycin group, the mRNA level of α-SMA, Snail1 (P<0.01) and HMGB1 (P<0.05) were declined, but mRNA level of E-cadherin (P<0.01), Foxo3a and FoxM1 (P>0.05) were ascendant in the gefitinib group. Meanwhile, western blot analysis showed reduced protein expressions of α-SMA (P<0.05), Snail1(P<0.01), HMGB1 (P<0.05) and p-Foxo3a/Foxo3a (P<0.01) in lung tissues, while expressions of E-cadherin (P<0.05), Foxo3a and FoxM1 proteins (P>0.05) were increased in the gefitinib group.ConclusionsIncreased activity of Foxo3a can down-regulate Snail1, which decreases the expression of α-SMA and increases the expression of E-cadherin, thereby attenuating bleomycin-induced pulmonary fibrosis in mice.
Objective To evaluate the efficacy of Gefitinib for patients with non-small-cell lung cancer (NSCLC). Methods We searched several databases, including MEDLINE (1991 to June 2008), The Cochrane Library (Issue 4, 2008) and CBMDisc (1978 to Feb. 2008). Randomized controlled trials (RCTs) were included in the meta-analyses, which were done using The Cochrane Collaboration’s RevMan 4.2 software. We also included retrospective case reports published in Chinese journals. Results Eight RCTs and 36 uncontrolled case reports were analyzed. The results of the RCTs showed that 250 mg/d Gefitinib had similar efficacy to 500 mg/d, but the side effect was significantly less for the lower dose. When used as a combined first-line treatment or a third-line treatment, Gefitinib was not superior to placebo on response rate, survival rate and life span. When used as second-line treatment, it did not prolong median survival, though it gave a higher response rate than placebo. Gefitinib caused many more side effects than placebo. Gefitinib exhibited similar efficacy to docetaxel in objective response rate [OR 1.18, 95%CI (0.84, 1.67), P=0.35], but was better for symptom and quality-of-life improvement [OR 1.58, 95%CI (1.33, 1.89), Plt;0.00001]. The overall uncontrolled clinical studies showed the following results: complete response rate was 2.2%, partial response rate was 25.8%, disease stable rate was 40.0% and progressive disease rate was 32.0%. The average median survival time was 8.9 months; the average time to progressive disease was 5.2 months, and the 1-year survival rate was 44.2%. The average median survival from EAP studies (6.9 months) was shorter than that for all the studies as well as the registered clinical trials (10.0 months). The average periods to progressive disease for registered clinical trials (3.2 months) and EAP studies (4.4 months) were somewhat shorter than that found for all studies combined, though response rate and 1-year survival rate were similar. Since there was no controlled clinical study, it was hard to conclude from the results whether Gefitinib brought any clinical benefit to NSCLC patients in China. Conclusion Gifitinib is not suitable as a combined first-line treatment or a third-line treatment for NSCLC. The clinical favor from gefitinib in the second-line treatment remains uncertain. There is not enough evidence to show whether Chinese people are more sensitive to Gefitinib, and its use in the second-line treatment of NSCLC needs to be tested further.
Objective To investigate the effects of gefitinib in the treatment of sarcomatoid carcinoma. Methods Clinical data of a case of sarcomatoid carcinoma was analyzed and related literatures were reviewed.Results A patient with sarcomatoid carcinoma was admitted with progressive dry cough,chest pain and dyspnea for 3 months. The patient was diagnosed as lung sarcomatoid carcinoma by thoracoscopy and treated with gefitinib. After 2 weeks treatment, symptoms disappeared and tumor was stable for 4 months. Literatures review suggested that sarcomatoid carcinoma is a rare malignant tumor. Treatment of sarcomatoid carcinoma includes surgery, chemotherapy and radiotherapy, but these methods show little effect in advanced patients. In our case, the patient with sarcomatoid carcinoma in stage Ⅳ was treated by gefitinib and showed favourable effect. Conclusions Advanced sarcomatoid carcinoma patients have a short life span and poor life quality. Gefitinib may provide these patients a feasible therapeutic approach.
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 systematically review the efficacy and safety of gefitinib versus pemetrexed as second-line treatment for advanced non-small cell lung cancer (NSCLC). MethodsDatabases including PubMed, The Cochrane Library (Issue 4, 2016), EMbase, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) about gefitinib versus pemetrexed as second-line treatment for advanced NSCLC from inception to April 2016. 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 11 RCTs involving 1 005 patients were finally included. The results of meta-analysis showed that: the rate of progression free survival (PFS) in the gefitinib group was superior to the pemetrexed group (HR=0.59, 95%CI 0.47 to 0.73, P<0.000 01). However, there were no significant differences between two groups in overall response rate (RR=1.28, 95%CI 0.86 to 1.90, P=0.22), disease control rate (RR=0.92, 95%CI 0.77 to 1.12, P=0.41) and the rate of overall survival (HR=0.75, 95%CI 0.56 to 1.01, P=0.05). The incidences of skin rash (RR=8.72, 95% CI 3.65 to 20.84, P<0.000 01) and diarrhea (RR=2.87, 95% CI 1.29 to 6.38, P=0.01) were significantly higher, but the incidences of neutropenia (RR=0.12, 95%CI 0.05 to 0.26, P<0.000 01) and fatigue (RR=0.46, 95%CI 0.30 to 0.72, P=0.000 6) were lower in the gefitinib group than those in the pemetrexed group. ConclusionGefitinib shows more superiority to pemetrexed, 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.
【摘要】 目的 评估吉非替尼治疗终末期（PS评分≥3分）非小细胞肺癌（NSCLC）的临床效果和生活质量改善情况。 方法 2008年5月-2010年6月共收治终末期NSCLC患者40例，其中19例患者采用吉非替尼治疗（治疗组），21例采用支持治疗+中药治疗（对照组）。 结果 治疗6个月后，治疗组19例患者中，CR 1例，PR 5例，SD 10例，PD 3例。治疗组有效率为31.5%（6/19），临床受益率为84.2%（16/19）。对照组21例中，SD 5例，PD 16例，无CR。对照组有效率为23.8%（5/21），临床受益率为 23.8%（5/21）。两组间有效率和临床受益率比较，差异均有统计学意义（Plt;0.05）。治疗组中位生存期为13.2个月，对照组中位生存期为4.5个月。 结论 吉非替尼可延长NSCLC患者的生存期，改善其生活质量。【Abstract】 Objective To evaluate the curative effect and life improvement of gefitinib on non-small cell lung cancer (NSCLC) which in the end stage. Methods Forty patients with end-stage NSCLC were treated from May 2008 to June 2010. Nineteen patients of them were treated with gefitinib (treatment group), 21 patients were treated with supportive care and traditional Chinese medicine treatment (control group). Results Six months after treatment, there are one patient with CR, five patients with PR, 10 patients with SD and three patients with PD in the treatment group. The effective rate of treatment group was 31.5% (6/19), clinical benefit rate was 84.2% (16/19). There are five patients with SD, 16 patients with PD, and no one with CR in the control group. The effective rate of the control group was 23.8% (5/21), clinical benefit rate was 23.8% (5/21). The differences of effective rate and clinical benefit rate between two groups were statistically significant (Plt;0.05). The median survival period of the treatment group and control group were 13.2 and 4.5 months respectively. Conclusion Gefitinib can extend the lifetime of NSCLC patients and improve their quality of life.