Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

Objective： To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer （NSCLC）. Methods： A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results： A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate （RR） was 36.0% （32/89）, and the disease control rate （DCR） was 69.7% （62/89）. RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma （P〈0.05）. The symptom improvement rate was 57.3% （51/89）, and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 （33.7%）] and diarrhea [15/89 （16.9%）]. The level of toxicity was typically low. Conclusions： The use of icofinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Icotinib hydrochloride对人涎腺腺样囊性癌细胞增殖的影响

分别应用0(对照组)、5、10、20、40、80μmol·L-1icotinib hydrochloride(盐酸埃克替尼)处理体外培养的人涎腺腺样囊性癌(ACC-M)细胞,形态学观察icotinib hydrochloride作用12、24、48、72、96 h后ACC-M细胞的生长状态变化.用四甲基偶氮唑盐法检测不同浓度的icotinib hydrochloride作用不同的时间下ACC-M细胞的增殖抑制率.结果显示,icotinib hydrochloride作用后ACC-M细胞体积变小,胞质皱缩,细胞间隙增大,胞内颗粒增多,贴壁细胞变圆、漂浮.Icotinib hydrochloride抑制ACC-M细胞增殖.

Icotinib, an EGFR-TKI, for the treatment of brain metastases in non-small cell lung cancer:a retrospective study

Objective Treatment of brain metastases from non-small cell lung cancer(NSCLC) is a challenge because of the poor prognosis. Icotinib is a new type of oral epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) used in the treatment of advanced NSCLC. The aim of this study was to evaluate the efficacy of icotinib in NSCLC patients with brain metastasis.Methods This study reviewed records of 51 NSCLC patients with brain metastases who took icotinib 125 mg, 3 times a day. Response rate, progression free survival, and overall survival were analyzed. SPSS software version 17.0 was used for univariate analysis, and Cox regression analysis to analyze factors affecting survival. Results Thirty-six cases had partial response, 6 cases had stable disease, and 10 cases had progressive disease. In 31 cases, EGFR gene mutation test were performed. EGFR was mutated in 26 cases and was with wild-type in 5 cases. In patients with EGFR mutations, 23 patients responded to icotinib [the disease control rate(DCR) was 88.5%], significantly higher than in patients with wild-type EGFR(1 patient, DCR 20%)(P = 0.005). The overall median progression-free survival(PFS) was 7.6 months. PFS was longer in the patients with EGFR mutations than in those with wild type EGFR(7.8 months vs 1.2 months, P = 0.03). The overall median overall survival(OS) time was 10.7 months. OS was longer in patients with EGFR mutations than in those with wild type EGFR(15.1 months vs 6.7 months, P = 0.003). The main side effects of the treatment were skin rash and diarrhea; no stage 3 or 4 toxic effects occurred. Univariate analysis demonstrated that OS was related to sex, Eastern Cooperative Oncology Group performance status(ECOG PS), smoking history, and EGFR mutation. Multivariate analysis showed that OS was independently related to sex, ECOG PS, and EGFR mutations.Conclusion Icotinib has a favorable effect on NSCLC patients with brain metastases harboring EGFR mutations. Icotinib can be a new choice of treatment for brain metastases in patients with NSCLC harboring EGFR mutations.

The short-term efficacy of icotinib on the treatment of advanced non-small-cell lung cancer

Objective： The aim of the study was, （1） to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer （NSCLC）; （2） to explore whether there is difference in the efficacy of icotinib hydrochloride among the subgroups of sex, age, smoking history, classification of CEA, histological type, multi-line treatment and PS score. Methods： The study was conducted to collect 138 patients taking icotinib hydrochloride with advanced non-small cell lung cancer in hospitals of Dalian （China） from September 1st 2011 to June 14th 2012. All patients had taken icotinib hydrochloride （125 mg three times a day） until the disease was progressed or the adverse reactions could not be tolerated. During the period of taking it, other anti-tumor treatments were forbidden. We observed the symptoms, such as cough, short breath, hemoptysis, pain. The objective efficacy was evaluated by RECIST criteria, and the adverse reactions related to the treatment was assessed on the basis of NCl-CTC 3.0. Results： Of all patients, CR was 1 （0.7%）, PR was 59 （42.8%）, SD was 37 （26.8%）, PD was 41 （29.7%）. And ORR was 43.5% （60/138）, DCR 70.3% （97/138）. The DCR of females was 83.5% （71/85） versus 49.1% （26/53） of males. The difference of ORR and DCR between the two subgroups had statistical significance （X2 = 8.065, P = 0.05; X2 = 18.577, P = 0.000）. The difference of ORR and DCR between the subgroups of patients after or before 70 years old had no statistical significance. The difference of ORR and DCR between the subgroups of smoking and non-smoking had statistical significance （X2 = 8.492; X2 = 13.602）. The difference of ORR and DCR between the CEA subgroups had statistical significance （X2 = 14.141; X2 = 14.160）, showed 81 patients with abnormal CEA before the treatment with ORR 56.8.0% （46/81）, DCR 81.5% （66/81）; 57 patients of normal CEA before the treatment with ORR 24.6% （14/57）, DCR 52.6% （30/57）. The 36 patients （26.1%） using icotinib hydrochloride as the first-line treatment, 78 patients （56.5%） using icotinib hydrochloride as the second-line, 20 patients （14.5%） using icotinib hydrochloride as the third-line, and 4 patients （2.9%） with tyrosine kinase inhibitor （TKI） resistance, there was statistical difference of DCR among the multi-groups above （~2 = 11.734, P = 0.008）. ORR was 31.1% （14/45） versus DCR 53.3% （24/45） in 45 patients with PS 3-4 points, and ORR was 49.4% （46/93） versus DCR 78.5% （73/93） in 93 patients with PS 0-2 points, and there was statistical difference （X2 = 4.156; X2 = 9.149）. The main adverse reactions were rash （26.8%）, diarrhea （13.8%）, mild liver function abnormal （10.9%）. Conclusion： The short-term efficacy of icotinib hydrochloride on the treatment of advanced NSCLC is positive, and the relevant adverse reactions are mild. The efficacy is better when the patient is female, non-smoker, treated as first-line, with higher CEA before treatment and lower PS scores.

Durable response to pulsatile icotinib for central nervous system metastases from EGFR-mutated non-small cell lung cancer: A case report

BACKGROUND Central nervous system(CNS) metastases are a catastrophic complication of nonsmall cell lung cancer(NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains challenging.CASE SUMMARY We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor(EGFR). A standard dosage of icotinib(125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib(1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side effects.CONCLUSION This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases.

Lung adenocarcinoma harboring rare epidermal growth factor receptor L858R and V834L mutations treated with icotinib:A case report

BACKGROUND Epidermal growth factor receptor(EGFR)tyrosine-kinase inhibitors are widely used for the treatment of non-small-cell lung cancer with EGFR mutations.However,patients with rare,even compound EGFR mutations have different responses to EGFR-tyrosine-kinase inhibitors,which bring uncertainty to clinical treatment.CASE SUMMARY A 45-year-old female patient presented with a 3-mo history of cough and white sputum without chest pain.Chest computed tomography revealed lung spaceoccupying lesions and multiple lymphadenectasis.Bronchoscopy and pathology suggested lung adenocarcinoma.Compound variation of EGFR gene(exon 21 L858 R/V834 L)was detected in both tissue and circulating tumor deoxyribonucleic acid samples.As a result of next-generation sequencing and her family’s wishes,the patient was given oral treatment with icotinib hydrochloride(125 mg/d,tid)from March 21,2019 and has achieved stable disease for the last 1 year.CONCLUSION Non-small cell lung adenocarcinoma with EGFR L858 R/V834 L was treated successfully with icotinib,and it may be a new medication treatment option.

Pharmacoeconomic Study on the Treatment of Terminal Non-small Cell Lung Cancer with Icotinib and Pemetrexed Combined with Cisplatin

Objective To provide theoretical basis for clinical treatment of patients with terminal non-small cell lung cancer through the analysis of the cost and adverse reactions of the joint treatment of icotinib and pemetrexed combined with cisplatin.Methods The clinical data of the patients diagnosed with terminal non-small cell lung cancer were collected and analyzed according to different drug administration schedules(n=53 of each group).The efficacy,cost and adverse reactions were evaluated respectively,aiming to provide the pharmacoeconomic evidence for the clinical applications.Results and Conclusion There was no significant difference between the efficacy of the icotinib group and the pemetrexed combined with cisplatin group,but the cost of the icotinib group was much lower,and the adverse reactions such as leukopenia,anemia,vomiting and nausea were far fewer than those in the pemetrexed combined cisplatin group.Although the two methods have similar therapeutic effects,the icotinib group has lower cost and fewer adverse reactions.Thus,from the perspective of pharmacoeconomics,icotinib has its advantage over the traditional regimen on the treatment of terminal non-small cell lung cancer.

紫龙金联合埃克替尼对Lewis肺癌荷瘤小鼠免疫功能及肿瘤血管生成的影响

目的:探讨紫龙金联合埃克替尼对Lewis肺癌荷瘤小鼠免疫功能及肿瘤血管生成的影响。方法:选用无特定病原体(SPF)级C57BL/6雄性小鼠50只,随机取10只用于制备Lewis瘤细胞悬液,余40只于其右前肢腋窝皮下分别接种0.2 mL的Lewis瘤细胞悬液,建立Lewis肺癌荷瘤小鼠模型,并将其随机均分为模型组、紫龙金组、埃克替尼组、联合观察组,每组10只。对比各组肿瘤重量、肿瘤生长抑制率;用酶联免疫吸附试验(ELISA)法检测小鼠血管内皮生长因子、小鼠肿瘤组织白细胞介素2(IL-2)、肿瘤坏死因子α(TNF-α)、干扰素(IFN-γ)水平;流式细胞术检测小鼠脾脏免疫细胞比例。结果:与紫龙金组及埃克替尼组比较,联合观察组小鼠的肿瘤重量和小鼠肿瘤生长抑制率高(均P<0.05),血管内皮生长因子水平及微血管密度低(均P<0.05),CD4^(+)T、CD8^(+)T及B淋巴细胞比例高(均P<0.05),肿瘤组织的IL-2、TNF-α、IFN-γ水平低(均P<0.05)。结论:紫龙金和埃克替尼联合治疗具有协同作用,显著降低了Lewis肺癌荷瘤小鼠模型的肿瘤重量,抑制了血管生成,增强了免疫功能,减轻了炎症反应。

Tumor gene mutations and messenger RNA expression： correlation with clinical response to icotinib hydrochloride in non-small cell lung cancer

Background Molecular targeted drugs is now widely used in non-small cell lung cancer （NSCLC） clinical treatment. Icotinib hydrochloride is a new type of oral epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （EGFR-TKIs）. In this study, we examined the role of EGFR, K-RAS, B-RAF somatic mutations and EGFR mRNA expression in tumor specimens from advanced NSCLC patients as predicators of the efficacy of icotinib hydrochloride. Methods We analyzed tumor paraffin-embedded specimens, which were obtained from 14 of 40 patients with advanced NSCLC who enrolled in the stage I clinical trial of icotinib hydrochloride. Somatic mutations were evaluated by mutant-enriched liquidchip （MEL） technology, and EGFR mRNA expression was measured by branched DNA liquidchip （MBL） technology. Results In the 14 specimens, seven patients showed EGFR mutations, exon 19 deletion （3/7） and exon 21 point mutation （4/7）; and two patients showed K-RAS mutation. No mutations in EGFR exon 20. or B-RAF were detected. In patients with EGFR mutation, one patient developed progress disease （PD）, three patients had stable disease （SD）, two patients had partial responses （PR） and one patient had a complete response （CR）. In patients with wild-type EGFR, four patients had PD, three patients acquired SD, and none had PR/CR （P=-0.0407）. EGFR mutations were associated with better progress-free survival （PFS） （141 days vs. 61 days） but without a statistically significant difference （P=0.8597）, and median overall survival （OS） （-〉449 days vs. 140 days）. EGFR mRNA expression levels were evaluated （three high, eight moderate, one low, and two that can not be measured due to insufficient tumor tissue） and no statistically significant relationships was observed with response, PFS or OS. Conclusions The EGFR mutation rate was consistent with that reported in the Asian population, so the MEL technology is reliable for measuring EGFR mutation with high throughput and rapidity. EGFR exon 19 deletions and exon 21 point mutation are predictive biomarkers for response to icotinib hvdrochloride as second line treatment or above.

Phase I trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer

Background The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer （NSCLC） in a Chinese patient population. Methods This was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib （100 to 400 mg）, administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity. Results Forty patients with stage IIIB （15%） or IV （85%） NSCLC were included in the study. They had mainly adenocarcinoma （85%）, with a performance status （PS） of 0 （45%） or 1 （55%） and less than half the patients （45%） had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash （25%）, diarrhea, nausea and abdominal distention. One definite interstitial lung disease （ILD） was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one （2.5%） patient receiving 150 mg gained complete response （CR） that persisted for 44 weeks, seven （17.50%） patients had partial remission （PR）, and 18 （45%） patients had stable disease （SD）. The objective response including CR＋PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks （range： 12 to 32 weeks）. The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, response, adverse effect, or duration of the study was observed. Conclusions Icotinib, given as oral twice daily, showed favorable safety and tolerability. Mild and reversible rash, diarrhea, and nausea were the main adverse events. Antitumor activity was obvious at each dose in heavily pretreated patients. Pharmacodynamic evaluations and further phase II/III trials are in progress.

Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy

Background The preclinical experiments and several clinical studies showed icotinib,an oral epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor,in Chinese patients with advanced non-small cell lung cancer （NSCLC） who failed previous chemotherapy.We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients.Methods The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1,2011 to July 31,2012 were retrospectively analyzed.All patients were given icotinib treatment after the failure of previous chemotherapy.Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model.Results The objective response rate was 33/149 and disease control rate was 105/149.No complete response occurred.Median progression free survival （PFS） with icotinib treatment was 5.03 months （95％ CI：3.51 to 6.55）.Median overall survival was 12.3 months （95％ CI：10.68 to 13.92）.Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS.At least one drug related adverse event was observed in 65.8％ （98/149） of patients,but mostly grade 1 or 2 and reversible and none grade 4 toxicity.Conclusions lcotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy.It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

埃克替尼联合培美曲塞治疗表皮生长因子受体敏感突变非小细胞肺癌的疗效分析

目的分析埃克替尼联合培美曲塞治疗表皮生长因子受体(EGFR)敏感突变非小细胞肺癌(NSCLC)的疗效。方法选取2018年1月—2021年7月广东医科大学附属医院收治的152例晚期NSCLC患者为研究对象,以随机数字表法分为对照组和实验组,各76例。对照组口服埃克替尼,125 mg/次,3次/d。实验组在对照组基础上静脉滴注培美曲塞500 mg/m2,每3周给药1次。两组患者持续用药至疾病进展或毒性不耐受。比较两组持续治疗3个疗程的抗肿瘤疗效、肿瘤标志物、肺功能、免疫功能、肝功能及药物安全性,统计两组患者1年生存情况。结果治疗期间共脱落3例。实验组疾病控制率高于对照组(P<0.05)。实验组治疗前后胸甘激酶-1、神经元烯醇化酶、癌胚抗原、用力肺活量、第1秒用力呼气容积/用力肺活量、Th1/Th2、Th17/Treg、CD4^(+)/CD8^(+)的差值均高于对照组(P<0.05)。两组治疗前后丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素的差值比较,差异均无统计学意义(P>0.05)。实验组、对照组总药物不良反应发生率分别为25.33%和21.62%,差异无统计学意义(P>0.05)。截至随访结束,两组各失访2例。实验组73例患者存活59例,对照组72例患者存活56例,两组1年生存曲线比较,差异无统计学意义(P<0.05)。结论埃克替尼联合培美曲塞治疗EGFR敏感突变NSCLC患者,可增强近期抗肿瘤疗效,抑制肿瘤标志物合成,改善肺功能及免疫功能,且安全性良好。

Comparison of the inhibition potentials of icotinib and erlotinib against human UDP-glucuronosyltransferase 1A1

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 risks via UGT1A1 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 IC_(50) values of icotinib and erlotinib against UGT1A1-mediated NCHN-O-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 the Kivalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risks via UGT1A1 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 todesign 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 risks via UGT1A1 inhibition.

恩度联合埃克替尼对晚期非小细胞肺癌患者化疗敏感性、肿瘤标志物及预后的影响

目的 探讨恩度联合埃克替尼对晚期非小细胞肺癌(NSCLC)患者化疗敏感性、肿瘤标志物及预后的影响。方法 选取2019年1月至2020年8月我院收治的88例晚期NSCLC患者,随机分为观察组和对照组,每组44例。2组均采取培美曲塞^(+)顺铂(PP)化疗,同时对照组给予埃克替尼治疗,观察组给予恩度联合埃克替尼治疗。观察2组临床疗效、肿瘤标志物[糖类抗原(CA) 50、癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA) 21-1]、T淋巴细胞亚群、miR-34b、miR-204-5p、miR-158-5p表达水平,以及酪氨酸蛋白激酶2(JAK2)/信号转导和转录激活因子3 (STAT3)信号通路和不良反应。结果 2组临床总缓解率比较无统计学差异(P>0.05)。治疗后,观察组血清CA50、CEA、CYFRA21-1水平低于对照组(P <0.05);CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平高于对照组,CD8^(+)低于对照组(P <0.05);miR-34b、miR-204-5p、miR-158-5p表达水平高于对照组,JAK2、STAT3 mRNA表达水平低于对照组(P <0.05);无进展生存期高于对照组(P <0.05)。结论 恩度联合埃克替尼治疗晚期NSCLC疗效确切,可提高患者化疗敏感性及免疫功能,其作用机制可能与抑制JAK2/STAT3信号通路有关。

埃克替尼和吉非替尼靶向治疗晚期非小细胞肺癌的临床效果及结局分析

目的 分析埃克替尼和吉非替尼靶向治疗晚期非小细胞肺癌(NSCLC)的临床效果。方法 选取我院2018年4月至2021年4月收治的80例晚期NSCLC患者为研究对象,根据随机数字表法将其分为对照组(n=40,吉非替尼)和研究组(n=40,埃克替尼)。比较两组的治疗效果、血清指标、免疫功能、生存质量、治疗结局与不良反应发生情况。结果 两组的疾病控制率比较,差异无统计学意义(P>0.05)。治疗后,两组的癌胚抗原(CEA)、癌抗原125(CA125)、神经钙黏素mRNA、血管生成素-2(Ang-2)、血管内皮生长因子(VEGF)水平均降低,且研究组低于对照组(P<0.05)。治疗后,研究组的CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)高于对照组,CD8^(+)低于对照组(P<0.05)。治疗后,研究组的欧洲癌症研究与治疗组织生存质量核心量表(EORTC QLQ-C30)各维度评分高于对照组(P<0.05)。研究组的死亡率低于对照组(P<0.05);两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论 埃克替尼靶向治疗晚期NSCLC能够取得不输于吉非替尼的临床效果,可改善血清指标,提升免疫功能,延长生存时间,提高生存质量。

阿帕替尼联合埃克替尼治疗EGFR基因21号外显子L858R突变型NSCLC的临床观察

目的探究对表皮生长因子受体(EGFR)基因21号外显子L858R突变型非小细胞肺癌(NSCLC)采用阿帕替尼联合埃克替尼治疗的临床效果。方法将EGFR基因21号外显子L858R突变型NSCLC患者101例按随机数表法分为观察组(n=51)与对照组(n=50)。观察组采用阿帕替尼联合埃克替尼治疗,对照组仅采用埃克替尼治疗,治疗时间为56 d,2个周期。比较2组近期疗效、不良反应,并采用K-M生存分析曲线图分析2组远期疗效。结果观察组与对照组的客观缓解率(ORR)(74.51%vs 74.00%)与疾病控制率(DCR)(92.16%vs 94.00%)差异均无统计学意义(P>0.05);治疗期间2组未出现2级以上不良反应,观察组高血压和蛋白尿发生率分别为52.94%、50.98%,分别高于对照组的16.00%、10.00%,差异有统计学意义(P<0.05)。观察组生存率显著高于对照组(69.3%vs 43.1%),差异有统计学意义(P<0.05)。结论EGFR基因21号外显子L858R突变型NSCLC采用阿帕替尼联合埃克替尼治疗,可延长患者的无进展生存时间,不良反应的发生可接受。

安罗替尼联合盐酸埃克替尼一线治疗表皮生长因子受体突变阳性非鳞非小细胞肺癌合并脑转移患者的疗效和安全性分析

目的探讨安罗替尼联合盐酸埃克替尼一线治疗表皮生长因子受体(EGFR)突变阳性非鳞非小细胞肺癌合并脑转移患者的疗效和安全性。方法收集2018年6月至2021年11月于濮阳油田总医院就诊的EGFR突变阳性非鳞非小细胞肺癌合并脑转移癌患者61例,采用随机数字表法分为2组,观察组29例应用安罗替尼联合盐酸埃克替尼治疗,对照组32例应用盐酸埃克替尼单药治疗。比较2组患者的疗效、生存及不良反应。结果观察组客观缓解率、疾病控制率均高于对照组(χ^(2)=10.314,P=0.001;χ^(2)=5.710,P=0.017)。观察组颅内病灶客观缓解率、疾病控制率均高于对照组(χ^(2)=4.697,P=0.030;χ^(2)=4.638,P=0.031)。观察组患者中位疾病无进展生存期为10.3个月,(95%CI:9.25~11.35个月),对照组患者为7.4个月(95%CI:5.55~9.26个月;P=0.004)。观察组出现咯血、口腔黏膜炎疼痛、高血压发生率高于对照组(χ^(2)=7.015,P=0.008;χ^(2)=11.663,P=0.001;χ^(2)=14.962,P<0.001)。2组均未发生治疗中断以及与治疗有关的死亡。结论安罗替尼联合盐酸埃克替尼一线治疗EGFR突变阳性非鳞非小细胞肺癌合并脑转移患者可控制颅内病灶,延长疾病无进展生存期,且安全性相对较好。

埃克替尼治疗晚期非小细胞肺癌患者的临床效果

目的分析埃克替尼治疗晚期非小细胞肺癌(NSCLC)患者的临床效果。方法选取2019年4月至2022年4月我院收治的80例晚期NSCLC患者为研究对象,根据随机数字表法将其分为对照组(n=40,吉非替尼)和研究组(n=40,埃克替尼)。比较两组的治疗效果。结果研究组的疾病控制率高于对照组,差异具有统计学意义(P<0.05)。治疗后,研究组的miR-185-5p、miR-204-5p高于对照组,Lemur酪氨酸激酶3(LMTK-3)、POK红系髓性致癌因子(Pokemon)水平低于对照组,差异具有统计学意义(P<0.05)。治疗后,研究组的CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)优于对照组,差异具有统计学意义(P<0.05)。两组的并发症总发生率比较,差异无统计学意义(P>0.05)。研究组的体力状况优于对照组,差异具有统计学意义(P<0.05)。结论埃克替尼治疗晚期NSCLC患者的效果明显,可改善免疫指标及体力状况,更好地控制病情,改善预后,临床可进一步推广运用。

抗肿瘤药Icotinib hydrochloride

癌症是全世界首要的死因之一。据统计，2008年就有760万人死于癌症，其中有100万人死于肺癌，71％的肺癌死者是由于吸烟所致。表皮生长因子受体（EGFR）为受体酪氨酸激酶家族成员之一，其广泛表达于多种肿瘤（如乳腺癌、头颈癌和卵巢癌）中，故而成为抗癌治疗最具潜力的靶点之一。第1代EGFR抑制剂吉非替尼（gefitinib）和埃罗替尼（erlotinib）已获准用于经其他抗肿瘤药物治疗无效的晚期非小细胞肺癌（NSCLC）患者。该类药物的优点之一是避免了传统化疗药物所致的常见毒副作用（尤其是骨髓抑制）。然而，尽管该类药物的临床研究在一开始获得了成功，随后研究人员发现了一个问题，即EGFR抑制剂与以铂类药物为基础的化疗方案联用并不能有效改善生存期，