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Objective:To investigate the real-world efficacy of osimertinib and icotinib in metastatic non-small cell lung carcinoma (NSCLC) patients.Methods:A retrospective analysis was performed on clinical data of 151 newly-diagnosed patients with epidermal growth factor receptor (EGFR) -positive advanced NSCLC in Renmin Hospital of Wuhan University from March 2018 to May 2022. The patients were divided into osimertinib group ( n=53) and icotinib group ( n=98) according to treatment method. The objective response rate (ORR) , disease control rate (DCR) , progression-free survival (PFS) and overall survival (OS) were compared between the two groups. The factors influencing prognosis were analyzed by using Cox regression models. Subgroup analysis was performed according to metastatic site and EGFR mutation type. Results:ORR was 56.6% (30/53) and 59.2% (58/98) for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=0.09, P=0.759) . DCR was 83.0% (44/53) and 91.8% (90/98) for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=2.68, P=0.102) . The median PFS was 11.7 months and 11.8 months for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=0.06, P=0.802) . The median OS was not reached for patients in both the osimertinib group and icotinib group, with no statistically significant difference ( χ2<0.01, P=0.969) . The results of multivariate analysis showed that adrenal metastases ( HR=1.89, 95% CI: 1.04-3.41, P=0.036) was an independent prognostic factor for PFS. Gender ( HR=2.22, 95% CI: 1.08-4.58, P=0.031) and adrenal metastases ( HR=4.87, 95% CI: 1.76-13.46, P=0.002) were independent prognostic factors for OS. The results of the subgroup analysis showed that in patients with pleural metastases (median PFS: 11.7 months vs. 9.3 months, median OS: not reached vs. not reached) , adrenal metastases (median PFS: 8.7 months vs. 5.6 months, median OS: 20.0 months vs. 15.3 months) , 19DEL mutations (median PFS: 14.5 months vs. 13.3 months, median OS: not reached vs. 40.7 months) , the osimertinib group tended to have better survival outcomes. Conversely, in patients with contralateral lung metastases (median PFS: 8.3 months vs. 11.2 months, median OS: not reached vs. 40.7 months) , bone metastases (median PFS: 11.7 months vs. 11.8 months, median OS: not reached vs. 34.5 months) , liver metastases (median PFS: 8.7 months vs. 9.1 months, median OS: not reached vs. 23.8 months) , brain metastases (median PFS: 11.7 months vs. 15.3 months, median OS: 22.4 months vs. 35.3 months) and 21L858R mutations (median PFS: 9.5 months vs. 10.0 months, median OS: 22.4 months vs. not reached) , the icotinib group tended to have better survival outcomes, but with no statistically significant differences (all P>0.05) . Conclusion:Both osimertinib and icotinib have good therapeutic efficacy in patients with EGFR-positive advanced NSCLC, thus can be used as first-line treatment options.
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Clinical studies have established the clinical application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant targeted therapy. Compared with chemotherapy, the high efficiency and low toxicity of targeted therapy increases the survival benefit of patients. Icotinib was the first EGFR-TKI with independent intellectual property rights in China and the third EGFR-TKI to be marketed in the world. In order to summarize the experience of icotinib and other EGFR-TKIs in the adjuvant treatment of non-small cell lung cancer and further standardize and guide the clinical application of icotinib, experts from the China International Exchange and Promotive Association for Medical and Health Care and the Guangdong Association of Thoracic Diseases have organized an expert consensus on the adjuvant treatment of non-small cell lung cancer with icotinib, which is expected to provide clinicians with evidence-based medical evidences for postoperative targeted drug using.
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Humans , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms/surgery , Consensus , Mutation , ErbB Receptors/genetics , Crown Ethers/therapeutic use , Protein Kinase Inhibitors/therapeutic useABSTRACT
OBJECTIVE To compare the efficacy and safety of icotinib and gefitinib in the treatment of epidermal growth factor receptor （EGFR）-mutated advanced non-small cell lung cancer （NSCLC）. METHODS The data of 146 patients with EGFR- mutant advanced NSCLC of our Hospital from December 2015 to September 2021 were retrospectively analyzed and divided into the gefitinib group （73 cases） and the icotinib group （73 cases） according to the drug use. Patients in the gefitinib group were given 0.25 g of gefitinib tablets once a day orally by single drug or combined with conventional chemotherapy， while patients in the icotinib group were given 125 mg of icotinib hydrochloride tablets three times a day orally by single drug or combined with conventional chemotherapy. Short-term efficacy， progression-free survival （PFS） were observed； Cox regression model was used to analyze the factors affecting the prognosis of patients； the occurrence of ADR were observed in the two groups. RESULTS There was no statistically significant difference in the objective remission rate， disease control rate， and the incidence of grade 1-2 and grade 3-4 adverse drug reactions between the two groups （P＞0.05）； median PFS was significantly better in the icotinib group than in the gefitinib group （P＝0.048）. Results of subgroup analysis based on patients basic information showed that compared with the gefitinib group， PFS of female [HR＝0.57，95%CI（0.34，0.96），P＝0.031] and non-brain metastatic patients [HR＝0.58，95%CI（0.36，0.91），P＝0.017] in icotinib group were prolonged significantly. Results of regression model analysis showed that EGFR19 exon Del mutation [HR＝0.50， 95%CI（0.25，1.00）， P＝0.049]， EGFR21 exon L858R mutation [HR＝0.44， 95%CI（0.21，0.89）， P＝0.022] and icotinib treatment [HR＝0.65， 95%CI （0.44，0.96）， P＝0.030] were influential factors for prognosis. CONCLUSIONS The short-term efficacy and safety of icotinib and gefitinib in the treatment of EGFR- mutant advanced NSCLC are comparable， but icotinib can significantly prolong the patients’ PFS； EGFR19 exon Del， EGFR21 exon L858R mutations and icotinib treatment are factors affecting patients’ prognosis.
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Objective:To investigate the efficacy of concurrent chemoradiotherapy combined with icotinib targeted therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).Methods:A total of 89 EGFR-mutated NSCLC patients who were admitted to Shanxi Province Cancer Hospital from January 2017 to January 2019 were selected and divided into control group (45 cases) and observation group (44 cases) by random number table method. The control group received cisplatin combined with docetaxel concurrent chemoradiotherapy, the observation group received cisplatin combined with docetaxel concurrent chemoradiotherapy and oral icotinib targeted therapy. The blood coagulation function, immune function and levels of tumor markers were compared between the two groups.Results:There was no statistical difference in blood coagulation function, immune function and levels of tumor markers between the two groups before treatment (all P > 0.05). After treatment, the levels of fibrinogen [(13±4) g/L vs. (16±6) g/L], D-dimer [(1.0±0.8) mg/L vs. (1.4±1.0) mg/L], squamous cell carcinoma antigen [(0.97±0.23) μg/L vs. (1.11±0.21) μg/L], carbohydrate antigen 125 [(21±7) U/ml vs. (35±11) U/ml] and carcinoembryonic antigen [(2.2±0.3) ng/ml vs. (6.0±1.1) ng/ml] in the observation group were lower than those in the control group, and the differences were statistically significant ( t values were 2.84, 2.11, 3.08, 7.40 and 23.08, all P < 0.05). After treatment, the ratios of NK cells [(18±7)% vs. (15±4)%], cytotoxic T cells [(17.2±6.1)% vs. (14.7±3.6)%] and helper T cells [(31.03±0.11)% to (25.88±0.39)%] in the observation group were higher than those in the control group, and the differences were statistically significant ( t values were -2.91, -2.59 and 2.79, all P < 0.05). Conclusions:Concurrent chemoradiotherapy combined with icotinib targeted therapy can better improve the hypercoagulable state and levels of tumor markers in patients with EGFR-mutated NSCLC than simple concurrent chemoradiotherapy, and can improve the immune function of patients, which has good therapeutic efficacy.
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Objective To investigate the relationship between the treatment of EGFR-TKI icotinib and the prognosis of advanced lung adenocarcinoma patients with EGFR mutation. Methods Patients with advanced lung adenocarcinoma who had EGFR19 and 21 gene mutations and were treated with EGFR-TKI icotinib were enrolled. The relationships of clinical features, EGFR gene mutation subtypes, and different sites with patients'prognosis were analyzed. Results A total of 101 patients with advanced lung adenocarcinoma were included in this study, including 58 cases (57.4%) of EGFR gene exon 19 deletion mutation (EGFR Del19) and 43 cases (42.6%) of EGFR gene exon 21 point mutation (EGFR L858R). The objective response rate was 63.4%. The mPFS and mOS were 13 months and 27 months, respectively. In addition, the mPFS and mOS of EGFR Del19 and EGFR19 mutation 746-750 were higher than those of EGFR L858R and other EGFR mutations, respectively. Meanwhile, multivariate analysis showed that the number of metastatic sites and pleural metastasis were independent influencing factors of patients'OS (P=0.027; P=0.041). The mOS of patients with the number of metastatic sites ≤3 and without pleural metastasis were 29 and 27 months, respectively. Conclusion There is no significant difference found in overall survival of advanced lung adenocarcinoma patients treated with icotinib among different EGFR mutation subtypes and sites. Herein, the overall survival time is longer in patients with less than three metastatic sites and without pleural metastasis.
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OBJECTIVE： To evaluate the efficacy and safety of icotinib in the treatment of advanced non-small cell lung cancer （NSCLC）， and to provide evidence-based reference for clinical drug use. METHODS： Retrieved from the Cochrane library， PubMed， Sciencedirect， CNKI， Wanfang database and VIP， RCTs about icotinib or icotinib combined with routine treatment or with other drugs （trial group） versus routine treatment or other drugs （control group） in the treatment of advanced NSCLC were collected. After literature screening， data extraction and literature quality evaluation with Cochrane collaboration bias risk assessment tool 5.1.0， Meta-analysis was performed by using Rev man 5.3 statistical software. RESULTS： A total of 27 RCTs were included， involving 2 345 patients. Results of Meta-analysis showed that response rate [OR＝1.64， 95％CI（1.36， 1.97）， P＜0.000 01] and disease control rate [OR＝1.68， 95％CI（1.39， 2.04）， P＜0.000 01] in trial group were significantly higher than control group； the incidence of ADR in trial group [OR＝0.59， 95％CI（0.48， 0.72）， P＜0.000 01] was significantly lower than control group. CONCLUSIONS： Icotinib shows good efficacy and safety in the treatment of advanced NSCLC.
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Objective@#To compare the clinical efficacy of icotinib and gefitinib in the treatment of advanced(stage Ⅳ) lung adenocarcinoma patients with epidermal growth factor receptor(EGFR) sensitive gene mutation.@*Methods@#Fifty-four advanced(stage Ⅳ) lung adenocarcinoma patients with EGFR sensitive gene mutation were selected.According to the random number table method, the patients were divided into two groups, with 27 cases in each group.The icotinib group received icotinib hydrochloride targeted therapy, and the gefitinib group was orally given gefitinib.The clinical efficacy, quality of life score, adverse reactions, progression free survival(PFS) were compared between the two groups.@*Results@#There were no statistically significant differences in clinical curative effect between the two groups[complete remission(0 cases vs.0 cases), partial remission(9 cases vs.8 cases), stable(12 cases vs.14 cases), progress disease(6 cases vs.5 cases), objective response rate(33.3% vs.29.6%), disease control rate(77.8% vs.81.5%), Z=1.060, χ2=0.143, 0.100, all P>0.05]. After treatment, the differences of body function, social function, psychological function, common symptoms and side effects, specific modules in the gefitinib group were not statistically significant compared with those before treatment(t=1.402, 1.199, 1.840, 1.860, 1.275, all P>0.05). The icitinib group had better body function, psychological function, common symptoms, side effects and specific modules than before treatment(t=2.525, 3.335, 4.477, 3.778, all P<0.05). The psychological function, common symptoms and side effects, specific module life quality scores in the icotinib group were (39.72±4.23)points, (38.84±4.67)points, (38.94±4.56)points, respectively, which were higher than (37.08±5.14)points, (35.48±5.02)points, (35.85±4.97)points in the gefitinib group(t=2.061, 2.546, 2.380, all P<0.05). The incidence rate of Ⅰ-Ⅱ grade adverse reactions between the two groups had no statistically significant difference (χ2=4.667, P>0.05). The incidence rate of Ⅲ-Ⅳ grade adverse reactions of the icotinib group was 7.4%, which was lower than 25.9% of the gefitinib group(χ2=9.000, P<0.05). The total incidence rate of adverse reactions of the icotinib group was 40.7%, which was significantly lower than 70.4% of the gefitinib group(χ2=25.694, P<0.05). There was no statistically significant difference in mean PFS between the two groups in the 19delete mutation of EGFR gene(t=0.795, P>0.05). The average PFS of the icotinib group under EGFR gene 21L858R mutation was (14.62±3.85)months, which was longer than (10.73±5.61)months of the gefitinib group(t=2.971, P<0.05).@*Conclusion@#Icotinib, gefitinib in the treatment of advanced(stage Ⅳ) lung adenocarcinoma patients with EGFR sensitive gene mutation has similar clinical effect, but icotinib has higher safety, better tolerability, and can significantly improve the quality of life of patients, prolong the EGFR mutation of the 21L858R gene under the survival of patients.
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Objective@#To compared the clinical efficacy and pharmacoeconomics of gefitinib, erlotinib, icotinib in the treatment of non-small cell lung cancer (NSCLC), thus to provide guidance on drug selection for patients from safety, efficiency and economical aspects after medical reform.@*Methods@#The patients with NSCLC who admitted to the First Affiliated Hospital of China Medical University from 2014 to 2017 and treated by gefitinib, erlotinib, icotinib were selected (30 patients in each group). All the patients were diagnosed with NSCLC by tissue or cytology study and eventually disease progressed.The clinical efficacy of the three drugs was evaluated by retrospective analysis.Specially, cost-effectiveness and cost-utility were evaluated in terms of disease control rates(DCR) and quality adjusted life years(QALY), respectively.@*Results@#The results demonstrated that the progression free survival (PFS) of gefitinib, erlotinib and icotinib were 0.934 years, 1.079 years and 1.063 years, respectively.There was no statistically significant difference in PFS among the three groups(F=0.001, P=0.9 990). The major drug adverse reactions were rash, diarrhea and hepatic injury.The DCR of gefitinib, erlotinib and icotinib were 66.7%, 70.0% and 63.3%, respectively, the difference was statistically significant(χ2=0.300, P=0.8 607). The total cost of treatment in the three groups were 85 118 CNY, 70 513 CNY and 7 2213 CNY, respectively.The cost-utility ratios of three drugs were 91 133, 65 389 and 67 973, respectively.The cost-effectiveness ratios of three drugs were 1 276, 1 007 and 1 141, respectively.The erlotinib group had lower cost and higher utility (effectiveness). Sensitivity analysis showed that the conclusion was relative stable when the price of three drugs changed at the same time.@*Conclusion@#All of the three drugs are applicable for targeted therapy of NSCLC and show similar curative effect and adverse reaction.However, erlotinib shows better economy than others.
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Objective To study the clinical efficacy and safety of icotinib hydrochloride tablets combined with whole brain radiotherapy (WBRT) in non-small cell lung cancer (NSCLC) brain metastasis.Methods Fifty-three patients with NSCLC brain metastasis who were unable to tolerate chemotherapy or chemotherapy failed were selected in Baotou Central Hospital from October 2010 to April 2015.The patients were divided into the observation group (n =27) and the control group (n =26) using random number table method.Two patients were dropped out,one in the control group and one in the observation group.The patients in the control group were given WBRT (30 Gy/15 Fx).On this basis,the patients in the observation group were given icotinib hydrochloride tablets 125 mg,3 times a day.The patients were followed up for 18 months after the end of WBRT.The adverse reactions,clinical efficacy and the median survival times of the two groups were compared.Results The objective response rate of the observation group was 88.5％,which was higher than that of the control group (64.0％),and the difference was statistically significant (x2 =4.238,P =0.040).The incidence rates of skin rash and liver function damage in the observation group were 76.9％ and 15.4％,which were higher than those in the control group (0,x2=31.638,P ＜ 0.001;x2 =4.173,P =0.041).However,most of them were degree Ⅰ-Ⅱ,and they were tolerable.There were no significant differences in the incidence of myelosuppression and gastrointestinal reactions between the two groups (26.9％ vs.20.0％,x2 =0.339,P=0.560;34.6％ vs.28.0％,x2 =0.259,P=0.611).The median survival time in the observation group (9.0 months) was longer than that in the control group (7.0 months).The one year survival rate of the observation group was 33.3％,which was higher than that of the control group (23.1％),but the difference was not significant (x2 =0.676,P =0.411).Conclusion Icotinib hydrochloride tablets combined with WBRT in the treatment of brain metastasis with NSCLC can significantly improve the curative effects of brain metastasis,and it has a survival advantage,with tolerable adverse reactions.
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Objective To study the correlation of the prognosis of Icotinib administration with the expression levels of F-box and WD repeat domain-containing 7(FBW7) and myeloid cell leukemia-1 (MCL-1) in peripheral blood in elderly patients with advanced non-small-cell lung cancer.Methods A total of 76 patients aged 60 years or over diagnosed with non-small-cell lung cancer(NSCLC) with EGFR-sensitive mutations and under Icotinib treatment were enrolled in this study.FBW7 and MCL-1 mRNA expression levels in peripheral blood were detected by real-time quantitative PCR(RT-QPCR).The correlation of FBW7 and MCL-1 expression levels with clinical and histological parameters,overall survival (OS),and progression-free-survival (PFS) was analyzed.Results The FBW7 expression level and the MCL-1 expression level were negative correlated(r =-0.37,P ＜0.001).High FBW7 expression levels and low MCL-1 expression levels in peripheral blood were associated with improved therapeutic efficacy of Icotinib (P＜0.001) and extended OS and PFS.Cox regression analysis showed that the expression levels of FBW7 and MCL-1 in peripheral blood were independent influencing factors for OS and PFS.Conclusions Patients with high FBW7 expression levels and low MCl-1 expression levels are more likely to benefit from Icotinib treatment.Expression levels for either factor can be used as a predictive indicator for the effectiveness of Icotinib and provide guidance for its clinical use.
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Objective@#To explore the inhibitory effect of icotinib combined with cytokine induced killer (CIK) on various human lung adenocarcinoma cell lines in vitro.@*Methods@#The inhibitory effect of icotinib alone or icotinib combined with CIK on HCC827 and A549 cells was detected by cell counting kit-8(CCK-8). The apoptosis was detected by flow cytometry via Annexin V/PI staining. The effect of icotinib on CIK phenotype was detected by flow cytometry.@*Results@#The inhibitory rates of HCC827 cells treated with 1.5, 3, 6, 12 μmol/L icotinib were (5.64±0.05)%, (8.62±0.45)%, (14.57±0.65)% and (18.52±0.91)%, respectively. The inhibitory rates of A549 cells were (1.64±0.48)%, (2.09±0.28)%, (3.69±0.45)%, (4.41±0.58)%, respectively. At the same concentration, the inhibitory rate of HCC827 cells with icotinib treatment was significantly higher than that of A549 cells (P<0.05). When the effector/target ratio was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells co-cultured with CIK were (15.17±2.33)%, (42.59±7.18)%, (62.59±8.95)%, respectively, and the inhibitory rates of A549 were(16.99±2.81)%, (46.31±1.89)%, (58.24±4.23)%, respectively. The inhibitory rate of HCC827 cells co-cultured with CIK was not significantly different from that of A549 cells at the same effector/target ratio (P10∶1=0.299, P20∶1=0.318, P40∶1=0.366). When the effector/target ratio of CIK combined with 6 μmol/L icotinib was 10∶1, 20∶1 or 40∶1, the inhibitory rates of HCC827 cells were (37.07±3.50)%, (76.03±6.55)%, (80.34±10.69)%, respectively, and the inhibitory rates of A549 cells were(25.72±1.41)%, (52.76±3.82)%, (62.26±1.94)%, respectively. The inhibitory rates of 6 μmol/L icotinib combined with CIK were significantly higher than those of icotinib group and CIK group alone at the same effector/target ratio (P<0.05), except for the effector/target ratio at 40︰1 on A549 cells (P=0.089). Moreover, all of the combination index (CI) of combined group were <1 (P<0.05). The apoptotic rates of HCC827 and A549 cells induced by icotinib combined with CIK were significantly higher than those of icotinib group and blank control group (P<0.05), especially the proportion of late apoptotic or necrotic cells.Increasing effector/target ratio of CIK contributed to stronger inhibition(P<0.05). The expressional rate of CIK phenotype with or without icotinib treatment was not significantly different from each other(P>0.05).@*Conclusions@#EGFR mutant lung adenocarcinoma cells are more sensitive to icotinib, while the EGFR mutation status has no effect on the killing effect of CIK cells. icotinib combined with CIK has a synergistic effect on the inhibition of tumor growth, and icotinib has no any impact on the phenotype of CIK cells.
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Objective: To evaluate the clinical efficacy and side effects of icotinib combined with a subarachnoid space implantable pump for the treatment of leptomeningeal metastases (LM) from lung adenocarcinoma. Methods:Seven cases of LM from lung adeno-carcinoma with epidermal growth factor receptor mutation were included in the study from March 2011 to September 2015. With the aid of anesthetists, all patients were implanted with subarachnoid space implantable pumps to drain the cerebrospinal fluid (CSF) and then treated with icotinib (125 mg, three times a day) until disease progression or unacceptable toxicities. After 4 weeks, the efficacy and tolerability of icotinib were evaluated on the basis of symptoms, tumor markers from CSF, and brain gadolinium-enhanced magnet-ic resonance imaging scans. Results:Among the seven patients evaluated, no patient had complete response, two patients had partial response, four had stable disease, and one had progression. The patient who was progressive died at a month after therapy. The sur-vival time of all the other patients was more than 4 months. The common adverse effects of icotinib were skin rash and diarrhea, main-ly in grades 1 and 2. No infection of the local subarachnoid drainage tube was found in the abdominal wall. Conclusion:Icotinib com-bined with a subarachnoid space implantable pump for the treatment of LM from lung adenocarcinoma may be effective, and the tox-icities are tolerable. This method could also obviously alleviate the clinical symptoms and improve the quality of life of the patients, worthy of further study.
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Objective To compare the efficacy and safety of icotinib therapy alone versus icotinib combined with thoracic radiotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) patients with an activating epidermal growth factor receptor (EGFR) gene mutation.Methods A total of 83 patients with advanced NSCLC harboring an activating EGFR gene mutation was enrolled in this study.All the patients were randomly divided into 2 groups.Patients in group A (n =41) received thoracic radiotherapy (prescribed at 60-66 Gy) combined with icotinib (three times per day,125 mg once).Patients in group B (n =42) were given icotinib therapy alone (three times per day,125 mg once).Treatment was continued until disease progression or unacceptable toxicity or death.The primary end points were median progression-free survival (mPFS) and 12 month-PFS rate.The secondary end points included objective response rate (ORR),disease control rate (DCR) and adverse events.Results With a median follow-up of 18.2 months,mPFS was 15.2 months (95％ CI:12.2-17.4) in group A and 13.2 months (95％ CI:10.8-14.9) in group B (x2 =4.29,P=0.036).PFS rates of 12 months for group A and group B were 70.3％ and 61.2％,respectively.The ORR were 78.0％ vs.57.1％ (x2 =5.16,P =0.028),and the DCR were 95.1％ vs.92.9％ (P＞0.05) in groups A and group B,respectively.No grade 3-4 adverse events was observed in both groups except the rashes (4 cases in each group).Besides,10 patients had grade 1-2 radiation-related pneumonitis and 15 patients suffered grade 1-2 radiation-related oesophagitis in group A.Conclusions In advanced NSCLC patients with an activating EGFR gene mutation,the combination of thoracic radiotherapy and icotinib had achieved an improvement on ORR and PFS with good tolerance.Clinical trial registration Chinese clinical trial registry,ChiCTRINR-16010262.
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AIM To explore the curative effects,adverse events,effects on immunity function and cost-effectiveness of Aiyu Capsules (Cremastrae pseudobulbus,Solanum lyratum,Angelicae sinensis Radix,etc.) or Fufang Banmao Capsules (Mylabris,Ginseng Radix et Rhizoma,Astragali Radix,etc.) combined with icotinib hydrochloride in the treatment of advanced non-small cell lung carcinoma (NSCLC).METHODS One hundred and sixty patients with advanced NSCLC were randomly divided into three groups.The patients in icotinib hydrochloride group (n =80) took icotinib hydrochloride,125 mg each time,three times a day;the patients in Aiyu Capsules + icotinib hydrochloride group or Fufang Banmao Capsules + icotinib hydrochloride group were treated with Aiyu Capsules (40 cases,three pills each time,three times a day) or Fufang Banmao Capsules (40 cases,one pill each time,three times a day) combined with icotinib hydrochloride (125 mg each time,three times a day),respectively.Curative effects,adverse events,serum tumor markers,dendritic cell subsets and cost-effectiveness among the three groups were compared.RESULTS Eight weeks after the treatment,effective rates in the Aiyu Capsules + icotinib hydrochloride group (82.50％) and Fufang Banmao Capsules + icotinib hydrochloride group (97.5％) were significantly higher than that in the icotinib hydrochloride group (73.5％) (P ＜ 0.05).Six-month survival rates in the icotinib hydrochloride group,Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were 93.7％,97.5％ and 97.5％,respectively;one-year survival rates in the three groups were 53.7％,72.5％ and 75.0％,respectively;two-year survival rates in the three groups were 20.0％,37.5％ and 40.0％,respectively.One-year,two-year survival rates in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were significantly higher than those in the icotinib hydrochloride group (P ＜ 0.05).Myeloid dendritic cell (mDC) subsets' increases (d8week-d1) in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were significantly higher than that in the icotinib hydrochloride group (P ＜ 0.05).There was no statistical significance in plasmacytoid dendritic cell (pDC) subsets' change among the three groups (P ＞ 0.05).Changes of carcinoembryonic antigen (CEA),cytokeratin-19-fragment (CYFRA21-1),neuron-specific enolase (NSE) in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were higher than those in the icotinib hydrochloride group (P ＜ 0.05).Treatment costs in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were significantly lower than that in the icotinib hydrochloride group (P ＜ 0.05).No obvious statistical difference in adverse events was found among the three groups (P ＞ 0.05).CONCLUSION The curative effects and cost-effectiveness of Aiyu Capsules or Fufang Banmao Capsules combined with icotinib hydrochloride are better than those of icotinib hydrochloride alone in the treatment of advanced NSCLC.
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Objective To explore the effect of icotinib hydrochloride in the treatment of advanced non-small cell lung cancer (NSCLC).Methods 52 patients with advanced NSCLC were selected as the research subjects,and they were divided into conventional group and study group by the computer random grouping method,26 cases in each group.The conventional group took docetaxel treatment,and the study group took icotinib hydrochloride treatment.The treatment effect of the two groups was compared.Results The disease control rate of the study group was 84.62％,which was significantly higher than 57.69％ of the conventional group,the difference was statistically significant(x2 =4.591,P =0.032).The progression free survival of the study group was (5.54 ±0.23)months,which was longer than (4.52 ± 0.22) months of the conventional group,the difference was statistically significant (t =16.341,P =0.000).The incidence rate of adverse reaction of the study group was 23.08％,which was significantly lower than 50.00％ of the conventional group,the difference was statistically significant(x2 =4.063,P =0.044).Conclusion The effect of icotinib hydrochloride in the treatment of advanced NSCLC is distinct,and drug safety is relatively high,it can help prolong survival of patients,and it is worthy of popularizing practice.
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Objective To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations.Methods Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study.The response rates , progress free survival ( PFS) , overall survival ( OS ) , and the safety were analyzed.Results Ninety advanced adenocarcinoma patients were enrolled in this study , 44 patients had partial response ( PR ) , 42 patients had stable disease ( SD ) , 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%.The median PFS was 14.9 months (95%CI 13.5-16.3) and the OS was 37.0 weeks ( 95%CI 27.9 -46.1 ).Patients with brain metastases showed higher ORR ( P =0.049 ).Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P=0.007 ).The most common adverse events were grade 1 -2 skin rash (38 patients, 40.9%).Other adverse events included dry skin , oral mucositis, diarrhea and liver function injury.Three patients withdrew because of severe liver injury or skin rash.No treatment related mortality occurred .Conclusions Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.
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UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risksUGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The ICvalues of icotinib and erlotinib against UGT1A1-mediated NCHN--glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with thevalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risksUGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration-time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risksUGT1A1 inhibition.
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Objective To evaluate the efficacy and adverse effects of icotinib in the treatment for non-small cell lung cancer (NSCLC) patients with brain metastases. Methods This study was performed at Tongji Hospital Cancer Center over the period between September 2011 and November 2015. Thirty cases of advanced NSCLC patients with icotinib monotherapy were enrolled, all with brain metastases, the median follow-up time being 24 months (5.5-49.0 months), with no case censored. The follow-up rate was 100%, and the data of efficacy and adverse effects were collected. Results The intracranial progression-free survival (iPFS) was 9.6 months, while no patient exhibited complete remission (CR), 8 patients showed partial remission (PR) and 14 showed stable disease (SD) in the intracranial foci. The intracranial disease control rate (DCR) was 73.3%, and the objective remission rate (ORR) was 26.7%. The extracranial progression-free survival (ePFS) was 10.1 months, while no patient exhibited CR, 11 patients showed PR and 11 patients showed SD in the extracranial foci. The extracranial DCR was 73.3%, and the ORR was 36.7%. The one-year survival rate was 63.8% in all the 30 patients. Twelve (40.0%) of the total 30 patients developed rash, five (16.7%) developed grade 1 diarrhea, one (3.3%) developed grade 2 transaminase elevation. None of the patients experienced headache, nausea, vomiting, fatigue, etc. Conclusion Icotinib hydrochloride is effective and safe for NSCLC patients with brain metastasis.
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Objective This research is aimed to investigate the efficacy and toxicity of icotinib for lung adenocarcinoma pa-tients with poor performance status and unknown EGFR gene status .Methods A total of 27 lung adenocarcinom patients with poor Eastern Cooperative Oncology Group-Performance status(ECOG-PS) and unknown EGFR gene status referred to Chongqing Canc-er Institute from August 2012 to August 2014 were analyzed .Icotinib (125 mg) was orally administered three times per day .Asess the efficacy and adverse reaction ,calculate survival rates .Results Among the 27 patients ,the objective response rate(ORR) and disease control rates(DCR) were 29 .6% and 81 .5% ,respectively .The median progression free survival time was 6 .0 months .A to-tal of 70 .4% of patients had an significant improvment in ECOG-PS scores ,following icotinib treatment (Z= - 2 .157 ,P= 0 .031) . Fatigue ,anorexia and diarrhea were the most frequent adverse reaction ,which defined as grade 1 to 2 rashes .Conclusion Lung ade-nocarcinoma patients with poor performance status and unknown EGFR gene status may benefit from icotinib therapy ,and patients were tolerated well .
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Objective To explore the influence of icotinib in the apoptosis of the human salivary adenoid cystic carcinoma cells ACC-M, and to clarify the mechanism of icotinib for the treatment of salivary adenoid cystic carcinoma.Methods The ACC-M cells were randomly divided into control group,2,4,8μmo1·L-1 icotinib groups,p38-MAPK inhibitor SB203580 (20μmol· L-1 )group,SB203580 (20 μmol· L-1 )+4μmo1 · L-1 icotinib group;the cells were collected 4 h after treatment.The viability of ACC-M cells was measured by MTT assay.The apoptosis of ACC-M cells was assessed by caspase-3 activity kit. The expression of p-p38-MAPK protein was determined by Western blotting analysis.Results Compared with control group,the inhibitory rates of growth of the ACC-M cells in icotinib groups were significantly decreased (P<0.05 ), and the activities of caspase-3 were increased (P<0.05),and the expression levels of p-p38-MAPK were significantly increased (P<0.05).Compared with 4μmo1·L-1 icotinib group,the expression level of p-p38-MAPK in SB203580+icotinib group were decreased (P < 0.05 ), and the activity of caspase-3 was decreased dramatically (P < 0.05 ). Conclusion Icotinib may induce the apoptosis of ACC-M cells through the activation of p38-MAPK signaling pathway.